ESCHERICHIA COLI 0157:H7 PROTEINS AND USES THEREOF

20220105167 · 2022-04-07

    Inventors

    Cpc classification

    International classification

    Abstract

    The present invention is direct to isolated polypeptides comprising or consisting of: an amino acid sequence selected from the group consisting of SEQ ID NOs: 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47 or 48; or (a) a variant and/or fragment of (a), for example: (i) a variant of (a); (ii) a fragment of (a); or (iii) a variant of a fragment of (a); together with corresponding isolated nucleic acid molecules, vectors, host cells, methods of production, vesicles, binding moieties, pharmaceutical compositions, kits, methods of treatment and medical uses.

    Claims

    1. An isolated polypeptide comprising or consisting of: (a) an amino acid sequence selected from the group consisting of SEQ ID NOs: 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47 or 48; or (b) a variant and/or fragment of (a), for example: (i) a variant of (a); (ii) a fragment of (a); (iii) a variant of a fragment of (a).

    2. The isolated polypeptide according to claim 1, wherein (a) is selected from the group consisting of SEQ ID NOs: 25, 26 and 27.

    3. The isolated polypeptide according to any preceding claim, wherein (b) exhibits at least 60% sequence identity to an amino acid sequence listed in (a), for example, at least 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99.5% sequence identity to an amino acid sequence listed in (a); (iii) wherein the at least 60% sequence identity is exhibited over at least 60% of the amino acid sequence listed in (a), for example, a contiguous amino acid sequence spanning at least 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the amino acid sequence listed in (a); or (iv) wherein the at least 60% sequence identity is exhibited over at least 10 contiguous amino acids of the amino acid sequence listed in (a), for example, at least 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 1500, 2000, 2500, 2600, 2601, 2602, 2603, 2604, 2605, 2606, 2607, 2608, 2609, 2610, 2611, 2612, 2613, 2614, 2615, 2616, 2617, 2618 or 2619 contiguous amino acids of the amino acid sequence listed in (a).

    4. An isolated nucleic acid molecule comprising or consisting of: (C) a nucleic acid sequence selected from the group consisting of selected from the group consisting of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24; or (D) a fragment, variant and/or fusion of (A).

    5. A vector comprising a nucleic acid molecule defined in claim 4.

    6. A host cell comprising a nucleic acid molecule defined in claim 4 or a vector as defined in claim 5.

    7. A method for producing a polypeptide according to any one of claims 1-3: comprising or consisting of the steps of culturing a population of host cells according to claim 6 under conditions in which the peptide is expressed, and isolating the peptide therefrom.

    8. A vesicle comprising one or more polypeptide defined in claim 1.

    9. The vesicle according to claim 8, wherein the vesicle is derived from the membrane of a cell, for example, a Gram positive bacteria membrane vesicle or a Gram negative bacteria outer membrane vesicle (OMV).

    10. A binding moiety capable of specifically binding to one or more polypeptide defined in claim 1.

    11. A pharmaceutical composition comprising a polypeptide defined in claim 1, a nucleic acid molecule defined in claim 4, a vector as defined in claim 5, a host cell as defined in claim 6, a vesicle as defined in claim 8 and/or a binding moiety as defined in claim 10.

    12. A kit comprising or consisting of a polypeptide defined in claim 1, a nucleic acid molecule defined in claim 4, a vector as defined in claim 5, a host cell as defined in claim 6, a vesicle as defined in claim 8, a binding moiety as defined in claim 10 and/or a pharmaceutical composition as defined in claim 11; and (optionally) instructions for use.

    13. A polypeptide defined in claim 1, a nucleic acid molecule defined in claim 4, a vector as defined in claim 5, a host cell as defined in claim 6, a vesicle as defined in claim 8, a binding moiety as defined in claim 10 and/or a pharmaceutical composition as defined in claim 11, for use in medicine.

    14. A polypeptide defined in claim 1, a nucleic acid molecule defined in claim 4, a vector as defined in claim 5, a host cell as defined in claim 6, a vesicle as defined in claim 8, a binding moiety as defined in claim 10 and/or a pharmaceutical composition as defined in claim 11, for use in preventing or treating bacterial infection and/or symptoms thereof.

    15. The use of a nucleic acid molecule defined in claim 4, or a binding moiety as defined in claim 10, for detecting the presence of bacteria.

    Description

    [0275] Preferred, non-limiting examples which embody certain aspects of the invention will now be described, with reference to the following figures:

    [0276] FIG. 1. E. coli K12 engineering to generate Generalized Modules for Membrane Antigens (GMMA). NOMV and GMMA were isolated by ultracentrifugation from supernatants of E. coli K12 WT and K12 ΔtolR::cat (A) Negative staining of native NOMV released from a wild-type E. coli K12 observed by transmission electron microscopy (TEM). NOMV from K12 WT strain appeared as closed spherical particles and homogeneous in shape with a size ranging from 20 to 100 nm. (B) Negative staining of GMMA produced by the K12 tolR::cat (K12tolR::cat) strain analyzed by TEM GMMA from tolR mutant were released in higher amount (size ranging from 20 to 200 nm), and some of them showed an atypical shape characterized by more than one membrane layer (magnification 120,000×). (C) SDS Page (4-12% bis-tris polyacrylamide) of membrane vesicles (NOMV and GMMA) purified from 75 ml of culture supernatants. Total protein content was quantified and 50 ug of GMMA obtained from K12 ΔtolR::cat sample was loaded into the gel. An equivalent volumetric amount of 15 NOMV from K12 WT obtained from 75 mL of supernatant was loaded and separated by SDS-PAGE. The tolR mutant showed an extensive protein profile in the supernatant compared to wild type. SDS-PAGE comparison of these preparations showed that the tolR mutant was able to yield 25-fold more vesicles than wild-type strain in terms of total protein content.

    [0277] FIG. 2. Antigen delivery into GMMA. (A) Scheme of the antigens cloned into pBAD with flag-tag. The three selected candidates were cloned into a pBAD vector using their own signal peptide. A flag-tag was inserted after the signal peptide of each protein. (B) Western blot of MC001, MC007 and MC020 independently fused to a flag-tag. Each construct was independently transformed in the K12tolR::cat mutant and induced with arabinose. The western blots show the expression of the flag-fused antigens (*) on GMMA recovered from these 16h cultures, in comparison to the GMMA-K12.

    [0278] FIG. 3. Vaccination with GMMA-MC001 reduces bacteria colonization feces, colon and caecum. (A) Graphic representation of bacterial counts in feces from challenged mice at Days 1-7 post-challenge. The mice immunized with GMMA-MC001 showed significant reduction in bacterial shedding at day 6 (≈2-logs, **P value=0.0033) and day 7 (≈4-logs reduction, **P value=0.0037) compared to the mice immunized with GMMA-K12. (B) The bacterial colonization in colon was reduced in mice immunized with GMMA-MC001 (≈3-logs, ***P=0.0003) and GMMA-MC007 (≈2-logs, **P=0.0068) compared to the mice immunized with GMMA-K12. (C) As for bacteria counts in caecum at day-7 post-challenge a significant reduction of bacteria was observed in mice immunized with GMMA-MC001 (=5-logs, ***P=0.0006) and GMMA-MC007 (≈3-logs, **P=0.0012), compared to mice immunized with GMMA-K12. The plots represent individual average and standard error of the mean (SEM) of individual mice. Significant differences in colonization were calculated by Mann-Whitney.

    [0279] FIG. 4. Specific total IgG response after immunization. Serum was collected from vaccinated animals previous the first immunization and 2 weeks post third immunization. Specific IgG antibody relative titers of GMMA over expressing the antigens or recombinant protein were measured by ELISA assays. Data are shown as mean of each group. (A) The GMMA vaccines were able to trigger the immune response, compared to pre-immune sera/PBS-alum group. However, the total IgG showed no significant difference among the GMMA groups. (B) The further test of specific IgG against the recombinant proteins form of each antigen, showed a significant difference of GMMA-MC001 (**P=0.0076) and GMMA-020 (**P=0.0075) against GMMA-K12 group. The endpoint titer of a sample is defined as the reciprocal of the highest dilution that has a reading above the cut-off. (C) The vaccines candidates were also able to generate specific antibodies against the antigens. By western blot assays, using recombinant proteins forms of each antigens as target, allowed the recognition only of the MC001 and MC020 recombinant proteins challenged with GMMA-MC001 and GMMA-MC020 sera respectively.

    [0280] FIG. 5. MC001 comparative protein modeling. (A) Structural model of MC001 obtained with SWISS-MODEL (depicted in green) using LpxR from Salmonella (3FID) as template (depicted in blue). (B) A detail of FIG. 9a show the conservation of the active site residues. (C) Sequence alignment between MC001 and LpxR from Salmonella in which the residues of the active site are boxed.

    [0281] FIG. 6. The selected candidates are mainly present and conserved among EHEC strains. The gene distribution analysis (by BLASTP) shows the presence/absence of the antigens in a panel of 47 E. coli complete genomes. Black cells represent a sequence identity>=80% with a query coverage>=90%, white cells represent gene absence or presence with a sequence identity<80% and query coverage below 90%. FIG. 6A provides analysis for antigen candidates MC001-MC012; FIG. 6B provides analysis for antigen candidates MC013-MC024.

    EXAMPLES

    Introduction

    [0282] Enterohemorrhagic E. col (EHEC) are a major cause of large outbreaks mainly affecting developed countries. For instance, from 1982 to 2002, a total of 350 E. coli 0157 outbreaks were reported in the United States. EHEC infection causes diarrheal disease often associated with clinical complications like hemorrhagic colitis and hemolytic uremic syndrome (HUS). Antibiotic based therapy is discouraged due to their potential undesirable effect in releasing shiga-toxin from the bacteria. No licensed vaccine specific for human use against EHEC is currently available. In this study, candidate antigens were identified from the EHEC O157:H7 genome and used with the GMMA antigen delivery system to provide new potential vaccine candidates. In particular, one of the candidate antigens (MC001) was able to reduce intestinal bacterial colonization in a mouse model; to our knowledge this study is the first report describing a lipid A deacylase enzyme (LpxR) as an antigen candidate.

    Materials and Methods

    Bacterial Strains and Culture Conditions

    [0283] All bacterial strains were routinely grown in Luria Bertani (LB) media with antibiotic selection pressure if needed, at 37° C. The E. coli MACH1-T1R (Thermofisher) strain was used for cloning while BL21 DE3 (NEB) strain was used to express and purify the antigens as recombinant proteins. EHEC O157:H7 strain EDL933, is the prototype pathotype used in this study for antigen identification. The strain EHEC O157:H7 86-24 was used in the animal challenging experiments.

    Antigen Candidate Selection

    [0284] In silico antigen candidate identification was performed as follows. The 5675 CDS (coding DNA sequences) of EHEC O157:H7 EDL933 strain annotated genome (GeneBank sequence CP008957.1) were analyzed by PSORT software (Yu et al., 2010) to predict the cellular localization. TMHMM (http://www.cbs.dtu.dk/services/TMHMM/, (Krogh et al., 2001) was used for prediction of transmembrane regions in putative proteins.

    [0285] RNA-Seq mapping and reads per kilobase per million mapped reads (RPKM) (cutoff>10) calculation was performed using Geneious R9 software (http://www.geneious.com, (Kearse et al., 2012). Distribution and sequence variability analysis into 47 E. coli complete annotated genomes was performed BLASTP (Altschul et al., 1997) using a cutoff of 290% of query coverage and a 280% of sequence protein identity %). Only antigens present in more than 5 intestinal pathogenic E. coli strains were selected. Presence of antigen candidates in non-pathogenic E. coli K12 and/or BL21 strains was used as exclusion criterion.

    [0286] Cloning and recombinant protein production of antigen candidates. All candidate antigens were cloned and expressed as His-tagged fusion proteins without the predicted signal sequence. Prediction of the signal peptide was performed by Signal P (Nielsen, 2017). All fragments were amplified by PCR using primers listed in Table S4, using genomic DNA of E. coli EHEC O157:H7 EDL933 strain. The PCR amplicons were cloned into a pET-15b plasmid (Novagen, EMD Millipore) with a His-tag in the carboxyl-terminus by the polymerase incomplete primer extension (PIPE) method (Klock and Lesley, 2009) or the NEBUILDER HiFi DNA Assembly Master Mix (NEB). Plasmids were transformed in BL21-DE3 (NEB). Briefly, E. coli BL21(DE3) harboring pET-15b constructs were grown in ENPRESSO (BioSilta) following the manufacturer suggestions and using Isopropyl β-D-1-thiogalactopyranoside (IPTG) 0.01M (Sigma-Aldrich) for induction. After biomass collection, cultures were lysed by sonication. The suspension obtained was centrifuged and the supernatant passed through a Ni-NTAAgarose chelating column (Qiagen). Proteins were eluted using an immidazol concentration gradient. In the case of insoluble proteins, the purification-immidazol buffer contained urea 6 M. Protein concentrations were measured by PIERCE BCA Protein Assay Kit (Thermofisher).

    Construction of TolR Mutant

    [0287] The tolR mutant in a E. coli K12 was constructed by allelic maker exchange using the Lambda red system (Datsenko and Wanner, 2000). The tolR was interrupted with a chloramphenicol resistance cassette (cat). Briefly, the cat cassette was amplified using forward and reverse primers with ≈70-nucleotides tail homologous to the flanking region of tolR, Table S4. The PCR product was purified and used to transform E. coli K12 recipient cells (carrying the plasmid expressing the recombinase E, pKD46) as described previously (Datsenko and Wanner, 2000). The deletion of the tolR gene was confirmed by PCR genomic DNA amplification using primers specifically annealing to the genes upstream (tolQ) and downstream (tolA) to tolR.

    NOMV and GMMA Production

    [0288] For NOMV isolation the E. coli K12 MC4100 WT strain was grown at 37° C. in liquid Luria-Bertani medium. For GMMA production E. coli K12 ΔtolR::cat was grown at 37° C. in liquid Luria-Bertani (LB) medium containing 10 chloramphenicol (20 μg/ml) as previously described (Fantappie et al., 2014; Rossi et al., 2016). Briefly, 75 ml of media were inoculated with E. coli K12 WT or ΔtolR::cat and grown at 37° C., 150 rpm overnight (=16 hrs.). To recover the supernatants cultures were centrifuged for 30 min at 8,000 g and 0.22 μm filtered. These media were ultracentrifuged using propylene ultracentrifuge tubes (Beckman Coulter) at 32,000 rpm for 2h at 4° C. Pellets were washed with phosphate-buffered saline (PBS). Pellets were resuspended in 2 ml of PBS followed by 0.22-μm filtration. Vesicles were stored at 4° C. To determine the total protein content present in these preparations a quantification was performed by DC protein assay (Bio-Rad) based on the Lowry assay (Rossi et al., 2015)

    Negative-Staining Transmission Electron Microscopy

    [0289] A drop of 10 μL of GMMA or NOMV suspension was placed on copper formvar/carbon-coated grids and adsorbed for 2 minutes. Grids were then washed with few drops of distilled water and blotted with a Whatman filter paper. For negative staining, grids were treated with Uranyless EM stain (Delta Microscopy with Chromalys France) for 1 minute, air-dried and viewed through transmission electron microscope Hitachi H-7650 at 80 kV. Electron micrographs were recorded at a nominal magnification of 120,000×.

    Over-Expression of Antigens in GMMA

    [0290] To over express the MC001, MC007 and MC020 candidates in GMMA, the corresponding coding sequence including their own signal peptide was cloned into a pBAD-A plasmid (Thermofisher) using the NEBUILDER HiFi DNA Assembly Master Mix (NEB). Also, a Flag-tag sequence (DYKDDDDK (SEQ ID NO: 116)) was introduced between the signal peptide of each protein and the rest of their sequence. The generated constructs (pBAD-MC001F, pBAD-MC007F, pBAD-MC020F), were transformed into the E. coli K12 ΔtolR::cat mutant and induced with arabinose (0.01% in final concentration). The generated GMMA were named GMMA-MC001, GMMA-MC007 and GMMA-MC020. The GMMA not expressing any antigen and obtained by transforming the empty pBAD-A plasmid were named GMMA-K12.

    Mice Immunization and Colonization Model

    [0291] Five-weeks old BALB/c mice (Janvier) (10 mice per group) were immunized using either (a) PBS-alum hydroxide as adjuvant (ALHYDROGEL 2%, Invivogen), (b) GMMA-expressing the MC001 candidate (GMMA-MC001) plus adjuvant, (c) GMMA expressing the MC007 candidate (GMMA-MC007) plus adjuvant, (d) GMMA expressing the MC020 candidate (GMMA-MC020) plus adjuvant, or GMMA-K12 (GMMA not expressing any candidate) plus adjuvant. All GMMA preparations were formulated using 2 mg/ml alum hydroxide as adjuvant. Animals were immunized (Day 1) by intraperitoneal injections (i.p.) with 10 μg of GMMA plus alum hydroxide, and at day 21 and day 35 with 5 μg of GMMA plus alum hydroxide. Blood was collected from all the mice prior immunization and two weeks after the third dose. The challenge experiment was performed at day-49 and using the EHEC O157:H7 strain 86-24. Mice were treated with streptomycin 24-hours prior infection. Also, animals received cimetidine 2 hours before infection via i.p. The animals were infected with 5×10.sup.9 CFU via gavage. Animal monitoring was performed on a daily basis including weight, signs and symptoms surveillance. Mice displaying signals of illness and losing more than the 15% of the total weight were euthanized, collecting the colon and colon organs. Fecal pellets were collected every day from day 1 to day 7 post-infection. At day 7 the remaining mice were euthanized and their colon and colon organs were collected. This animal model was adapted from models previously reported (Mohawk and O'Brien, 2011; Garcia-Angulo et al., 2013; Garcia-Angulo et al., 2014). All animal experiments were reviewed and approved by the Auvergne Committee for Animal Experimentation C2EA (Agreement No 6065-2016071216144325V2).

    Enzyme-Linked Immunosorbent Assay (ELISA)

    [0292] Ninety-six well Maxisorp plates (Nunc, Thermo Fisher Scientific) were coated with 1 mg/mi of GMMA preparations antigens or 1 mg/ml of recombinant protein in PBS overnight (O/N) at 4 QC. Next day, plates were washed 3 times with T-PBS (0.05% Tween 20 in PBS, pH 7.4) and blocked with 100 μl 2% BSA (Sigma-Aldrich) for 1 hour at 37° C. Every incubation step was followed by triple T-PBS wash. Serum samples were initially diluted 1:200 in 2% BSA in T-PBS, transferred to coated-blocked plates and serially 2-fold diluted followed by 2-hours incubation at 37 QC. Then 100 μl/well of 1:2,000 diluted alkaline phosphatase-conjugated goat anti-mouse IgG (H+L) (Southern Biotech) were added and incubated for 2 hours at 37 QC. Bound alkaline phosphatase was visualized by adding SIGMAFAST p-Nitrophenyl phosphate (Sigma-Aldrich) After 30 minutes at room temperature, plates were analyzed at 405 nm in a microplate spectrophotometer. The endpoint titer of a sample is defined as the reciprocal of the highest dilution that has a reading above the cut-off (Frey, 1998).

    Western Blotting

    [0293] Western blots were carried out on whole cell extracts (wce), recombinant proteins or GMMA preparations. SDS page was performed in MES buffer (Thermofisher) and transferred to iBlot 2 nitrocellulose stacks (iBlot system, Thermofisher). To visualize transferred proteins, the membranes were stained with ponceau red. Then, membranes were blocked with 10% (w/v) blotting-grade blocker (Bio-Rad) in T-PBS. The membranes were later incubated with the respective mouse polyclonal antisera in a 1:1000 dilution in T-PBS-3% blocker 1 hr. at room temperature. Membranes were washed three times with T-PBS and then incubated with goat anti-mouse horseradish peroxidase-conjugated IgG (Dako antibodies) diluted (1:2000) in T-PBS-3% blocker. Colorimetric staining was performed using Opti-4CN Substrate Kit (Bio-Rad) following manufacturer instructions. To detect the FLAG-tag monoclonal ANTI-FLAG M2 secondary antibody was used (Sigma Aldrich).

    Comparative Structural Modelling

    [0294] Structural models of MC001 have been obtained by employing three different approaches: the threading/ab initio modelling method implemented in the I-TASSER pipeline (Roy et al., 2010), the membrane proteins-specific approach of MEMOIR (Ebejer et al., 2013) and the homology modelling method of SWISS-MODEL (Biasini et al., 2014). The search for suitable modelling templates has been carried out with PSI-BLAST (Position-Specific Iterated BLAST) (Altschul et al., 1997) sequence similarity search against the Protein Data Bank using the amino acid sequence of MC001 as a bait. While MEMOIR does not provide a proper quality assessment of the models, in the case of I-TASSER and SWISS-MODEL, the quality of the final models has been assessed through the parameters C-score and QMEAN4 (Benkert et al., 2009), respectively. The C-score is a confidence score calculated based on the reliability of threading template alignments and the convergence parameters of the structure assembly simulations. C-score values typically range between −5 and 2, higher values characterizing high confidence models and vice-versa. The QMEAN4 score is a linear combination of four statistical potential terms and is typically in the range 0-1, with higher values characterizing better quality models. MC001 models are characterized by a C-score of −5 and a QMEAN4 score of 0.74.

    Statistical Analysis.

    [0295] All of the statistical analyses were done using GraphPad Prism 7 software. Mann-Whitney (unpaired and non-parametric) and Student t test with threshold of P=<0.05 were used to analyse the data of the bacterial counts from the mouse colonization model and for the IgG antibody response.

    Results

    Identification of Antigen Candidates

    [0296] Potential antigens in EHEC O157:H7 EDL933 strain were identified by first analysing the putative cellular localization of the 5675 CDS from the annotated genome of EHEC O157:H7 EDL933 strain using the PSORT algorithm. We focused mainly on chromosome-encoded proteins predicted to be exported, surface associated proteins, outer-membrane-associated proteins, and proteins with an unknown localization. The selection criteria also included proteins greater than 200 amino acids and with less than 3 transmembrane repeats determined by the TMHMM algorithm. As result of this analysis, 329 potential antigen candidates were identified (Table S1). Next, RNA-Seq data available in NCBI Sequence Read Archive (SRA) was used to identify genes that were expressed at transcriptional level. These RNA-Seq dataset were previously generated using EHEC EDL933 strain grown in LB, LB with antibiotics, LB-agar media and cattle faeces (Landstorfer et al., 2014). Reads mapping on EHEC EDL933 resulted in 68 genes showing an absolute index number of ≥10 RPKM (reads per kilobase per million mapped reads) in at least one of the four growth conditions analysed (Table S2). Another selection criterion was based on gene variability and distribution analysis of these 68 EHEC EDL933 potential antigens on 47 complete genomes to select those present (query coverage: ≥290%) and conserved (sequence identity≥80%) in more than 5 different intestinal pathogenic E. coli strains. In addition, presence of antigen candidates in non-pathogenic E. coli such as K12 was used as exclusion criterion (FIG. 6). This in silico selection led to the identification of 24 potential antigens which were cloned, expressed and purified as recombinant His-tagged fusion proteins in E. coli. Polynucleotide and polypeptide sequences of these 24 antigen candidates are provided in Table 55. Of these, 12 were successfully purified as soluble and 12 as insoluble proteins (Table S3).

    [0297] The recombinant proteins were then used to immunize mice to produce polyclonal antibodies. These antibodies were subsequently tested in Western Blot analysis to assess the expression level of the corresponding potential candidate in the homologous EHEC O157:H7 strain, leading to the identification of 17 expressed proteins in standard laboratory growth conditions (Table 53). Finally, among these expressed proteins and as proof of concept, we focused on three potential antigens satisfying all the criteria mentioned herein. In particular, these three antigen candidates included an outer membrane protein (MC001), a putative aminopeptidase (MC007) and an autotransporter belonging to the AIDA family (MC020) (Table 1).

    TABLE-US-00002 TABLE 1 Features of the three selected antigen candidates Purified Selected Protein Annotation Localization Pfam Signal- recombinant Candidates ID feature prediction Domain Localization protein MC001 AIG67060.1 Putative outer Extracellular DUF2219 Non- Insoluble membrane Cytoplasmic protein MC007 AIG66424.1 Putative Unknown Unknown Non- Soluble aminopeptidase Cytoplasmic MC020 AIG69974.1 Pertactine Extracellular AIDA, Unknown Soluble precursor Pertactine

    Antigen Delivery in Generalized Modules for Membrane Antigens (GMMA)

    [0298] To express the three selected candidates in GMMA, we first generated an overblebbing E. coli K12 by mutating the tolR gene (K12 ΔtolR::cat). NOMV and GMMA were then isolated by ultracentrifugation from supernatants of E. coli K12 WT and the K12 ΔtolR::cat. The native OMV (NOMV) released from the wild-type E. coli K12 and GMMA preparation produced by the tolR mutant were observed by transmission electronic microscopy (TEM). This analysis showed that NOMV from K12 WT strain appeared as closed spherical particles and were homogeneous in shape with a size ranging from 20 to 100 nm (FIG. 1A). On the other hand, GMMA from tolR mutant were released in higher amount (size ranging from 20 to 200 nm), and some of these GMMA showed an atypical shape characterized by more than one membrane layer (magnification 120,000×)(FIG. 1B). SDS-PAGE (4-12% bis-tris polyacrylamide) comparison of membrane vesicles (NONV and GMMA) purified from 75 ml of culture supernatants showed that the tolR mutant yielded 25-fold more vesicles than wild-type strain in terms of total protein content (FIG. 1C). Total protein content was quantified and 50 ug of GMMA obtained from K12 ΔtolR::cat sample was loaded into the gel. An equivalent volumetric amount of NOMV from K12 WT obtained from 75 mL of supernatant was loaded and separated by SDS-PAGE. The tolR mutant showed an extensive protein profile in the supernatant compared to wild type.

    [0299] In order to express the three antigen candidates (MC001, MC007 and MC0021) in GMMA, each of their coding sequences was cloned in pBAD plasmid and the FLAG tag was inserted after their own signal peptide sequence (FIG. 2A). The generated constructs (pBAD-MC001F, pBAD-MC007F, pBAD-MC020F), were each independently transformed in the K12tolR::cat mutant and induced with arabinose. To test whether these plasmids were expressing the antigen candidates and incorporated into GMMA, we performed a western blot on GMMA recovered from 16h cultures using the anti-FLAG antibody. As shown in FIG. 2B all the three antigens were specifically recognized by the anti-Flag. These results indicate that the selected antigen candidates were expressed in GMMA and preparations of these vesicles can be used as an antigen delivery system.

    Immunization with MC001-GMMA Reduces EHEC Intestinal Bacterial Colonization in Mice

    [0300] To test the ability of the selected candidate antigens to prevent or reduce bacterial infection, an intestinal colonization model was setup using BALB/c mice. The EHEC O157:H7 86-24 strain was used for its ability to maintain stable intestinal bacterial colonization for 7-days post-infection using 5×10.sup.9 CFU (data not shown). Groups of ten mice were immunized with GMMA over-expressing the candidate antigens or with empty GMMA-K12 via intraperitoneal delivery at day 1, 21 and 35. At day 49, mice were infected with EHEC O157:H7 86-24 strain, via gavage. Fecal samples were collected in a daily basis for performing bacterial counts. GMMA-MC001 immunized mice showed a ≈3-log reduction (P=0.0001) in fecal bacteria number compared to PBS-alum immunized mice at day 5 after infection, while a ≈2-log and ≈4-log reduction (P value=0.0033 and 0.0037) was obtained in comparison to empty GMMA-K12 immunized groups at day 6 and 7 respectively (FIG. 3A). For ethical reasons, at day 5 most of the PBS-alum immunized mice were euthanized due their weight loss (>15% of initial body weight). By contrast, mice immunized with GMMA-MC007 and GMMA-MC020 preparations did not show significant reduction in fecal bacterial shedding in comparison to PBS-alum and GMMA-K12 immunized mice (FIG. 3A).

    [0301] At day 7 post infection, colon and caecum tissues were collected from all mice groups and bacterial count was performed. The number of bacteria in colon and caecum tissues was significantly reduced (3-logs and 5-logs, P=0.0003 and 0.0006 respectively) in mice immunized with GMMA-MC001 in comparison to mice immunized with GMMA-K12, while GMMA-MC007 immunized mice showed a reduction of =2-logs and %3-logs for colon and caecum respectively (P=0.0068 and 0.0012) (FIGS. 3B and 3C) compared to the mice immunized with GMMA-K12.

    Immunization with GMMA Expressing Antigen Candidates Induces Specific Antigen Antibody Response

    [0302] To assess the immune response induced by GMMA immunization per se and the possible contribution in raising specific immune response against the three antigen candidates (MC001, MC007 and MC020) expressed in GMMA, serum antibody levels were determined by ELISA.

    [0303] To measure the total level of immunoglobulins G (IgG), serum samples were collected from the mice before the first immunization (preimmune sera) and two weeks after the third immunization, before challenging mice. Microtiter plates coated with purified preparations of GMMA-K12 and each of the three GMMA carrying a antigen candidate showed higher total IgG levels in all the immunized groups versus the preimmune sera. A non-significant difference was found among the four GMMA immunized groups (FIG. 5A). To test whether there was an induction of a specific immune response attributable to the antigens expressed in GMMA, we perform ELISA assays using microtitre plates coated with the MC001, MC007 and MC020 recombinant proteins. A significant increase in antibody response was found for GMMA-MC001 (P=0.0076) and GMMA-MC020 (P=0.0075) sera in comparison to GMMA-K12 sera (FIG. 58). To confirm that the immunization with GMMA expressing these antigen candidates was able to generate antigen specific antibodies, we performed western blot assays, using MC001, MC020 or MC007 recombinant proteins as target. Only MC001 and MC020 recombinant proteins were detected using GMMA-MC001 and GMMA-MC020 sera respectively, while MC007 was not recognized by GMMA-MC007 serum.

    MC001 is Homologous to Salmonella typhimurium Lipid A Deacylase (LpxR)

    [0304] To obtain more insights about the structural features of the MC001 antigen candidate an in-silico analysis was performed. In order to find proteins with known structure and significant sequence similarity with MC001, its protein sequence was used to run a PSI-BLAST search against the Protein Data Bank (PDB) (Berman et al., 2000). This search retrieved as first hit the sequence of the Salmonella typhimurium lipid A deacylase (LpxR). Furthermore, a PSI-BLAST search over the non-redundant protein sequences database revealed a high sequence similarity also with LpxR from Vibrio cholerae, Yersinia enterocolitica and Helicobacter pylori. Structural MC001 models using the LpxR structure as a template (PDB code: 3FID (Rutten et al., 2009) were built by I-TASSER, MEMOIR and SWISS-MODEL software. All three generated models that were in agreement with each other and showing a pairwise Cα root mean square deviation being in all cases lower than 0.5 Å.

    [0305] FIG. 5A provides a representative MC001 structural model obtained with the SWISS-MODEL The MC001 model was composed of a 12-stranded β-barrel in which the β-strands were arranged in an antiparallel fashion in a structure that is quite common in porins and other cell membrane proteins. The high homology between MC001 and Salmonella typhimurium LpxR was confirmed by the presence in the active site of six conserved residues essential for Ca+2 binding and LpxR catalytic activity: (Salmonella/E. coli) Asn (9/31), Asp (10/32), Thr/Ser (34/56), His (122/144), Gln (118/140) and Glu (128/150) (FIG. 5B). Sequence comparison revealed that MC001 has the same length of the LpxR Salmonella orthologue (319 amino acids) and shares approximately 74% sequence identity and 93.73% sequence similarity (74% of identity with 93% query coverage) (FIG. 5C).

    Discussion

    [0306] In this study, we identified 329 potential antigen candidates starting from the 5675 CDS of the EHEC O157:H7 EDL933 annotated genome. Further, to determine whether these candidates are expressed during infection or in vitro thus having a higher potential to be immunogenic we took into account the expression at the RNA level. Exploiting previously generated RNA-Seq dataset (Landstorfer et al., 2014) we identified antigens expressed in at least one out of four analyzed conditions, and selected potential antigens possibly present and conserved in more than a single intestinal pathotype. Following these criteria, we selected 24 candidate antigens; 17 of these 24 were found to be expressed also at the protein level in standard laboratory growth condition. Among this antigen panel, 12 proteins were predicted to be outer membrane associated proteins, three with extracellular localization and nine unknown.

    [0307] On the basis of these observations we used GMMA to express and deliver these candidate antigens (Berlanda Scorza et al., 2012; Bartolini et al., 2013; Daleke-Schermerhorn et al., 2014; Fantappie et al., 2014); GMMA is a system that has been successfully used for expression of properly folded membrane associated recombinant antigens and to induce functional immune responses (Bartolini et al., 2013). Also, GMMA can be a useful delivery system because the presence of native proteins on the membrane surface can act as self-adjuvants, helping to elicit an immune response (Kaparakis-Liaskos and Ferrero, 2015). However, in native conditions, blebs are recovered in small quantity and as consequence E. coli strains may be genetically modified by deletion of the tolR gene to enhance the level of vesicle production (Bernadac et al., 1998; Berlanda Scorza et al., 2012). In a first attempt, we introduced the tolR mutation in EHEC in which Stx was deleted to avoid possible release of toxins into the vesicles. Once these purified blebs were used to immunize mice we observed sick animals, showing bristled hair, lethargic behavior and lose of weight (data not shown). For this reason, we constructed a tolR mutant in an avirulent E. coli K12 which was able to release higher amounts of blebs in comparison to the wild-type K12. A small fraction of these vesicles when observed in TEM showed an atypical shape characterized by more than one membrane layer (double-bilayer) a characteristic observed by Perez-Crutz et al., (Perez-Cruz et al., 2013; Perez-Cruz et al., 2016). In the present study, we used GMMA for antigen expression and delivery. As proof of concept we selected three out of the 24 candidate antigens, including an outer membrane protein (MC001), a putative aminopeptidase (MC007) and an autotransporter (MC020) for expression in GMMA. Two out of the three selected candidate antigens (MC001 and MC020) showed typical features of membrane associated proteins, while for the MC007 the putative cellular localization was unknown. In addition, the MC001 candidate when purified as recombinant protein was obtained as insoluble form. Thus, we reasoned that the expression and delivery of these antigen candidates in GMMA would increase their antigenic potential since they could be presented in their native conformation. Our data showed that all the three candidates expressed by GMMA were specifically recognized by the anti-Flag antibody.

    [0308] For testing the ability of the selected candidate antigens to prevent or reduce bacterial infection, an intestinal colonization model was setup using BALB/c mice. This animal model was adapted from the previous animal models of infection for EHEC and Garcia-Angulo and colleagues (Mohawk and O'Brien, 2011; Garcia-Angulo et al., 2013). Although mice did not develop the symptoms associated with diarrheal disease as observed in humans, these murine models of E. coli O157:H7 infection, based on streptomycin-treated Balb/c mice, are promising for EHEC colonization and candidate vaccine testing (Mohawk and O'Brien, 2011; Garcia-Angulo et al., 2013). Our data indicated that a stable EHEC intestinal bacterial colonization for 7-days post-infection using 5×10.sup.9 CFU was maintained in the animals, and immunization with GMMA-K12 did not result in toxicity. We showed that intraperitoneal immunization using MC001 was able to significantly reduce EHEC colonization in mice feces (day 6 and 7), colon and caecum tissues (day 7), in comparison to immunization with empty GMMA-K12. For MC007 a less significant reduction was observed in colon and caecum tissues.

    [0309] Moreover, the immune response of the treated mice not only showed high titers of total IgG in the GMMA-MC001 vaccinated group, but also IgG specific to MC001. In fact, MC001 recombinant protein was recognized by GMMA-MC001 serum indicating this antigen candidate was associated with membrane vesicles and also easily accessible to immune system.

    [0310] In Western Blot, MC020 recombinant protein was detected by its respective GMMMA serum, and in agreement with the ELISA results showing higher IgG titer in comparison with GMMA-K12; this was not the case for MC007.

    [0311] As MC001 was indicated by these studies to be a promising antigen candidate, we used bioinformatic pipelines to predict molecular model by homology. BLAST analysis showed that MC001 was homologous to the Salmonella typhimurium lipid A deacylase (LpxR) and shared similarity also with LpxR from Vibrio cholerae, Yersinia enterocolitica and Helicobacter pylori. Structural MC001 model using the Salmonella typhimurium LpxR as a template revealed a structure composed of a 12-stranded β-barrel in which the β-strands were arranged in an antiparallel fashion. The high homology between MC001 and Salmonella typhimurium LpxR was also confirmed by the presence in the active site of six conserved residues essential for Ca+2 binding and LpxR catalytic activity. In addition, we showed that MC001 was present and conserved among different EHEC strains as Sakai, 026:H11, 0103:H2 and EPEC genomes.

    [0312] Recently, it has been reported that LpxR can play an important role in pathogenesis by removing the 3′-acyloxyacyl group of lipid A (the hydrophobic anchor of lipopolysaccharide, LPS). This modification increases the ability of Salmonella Typhimurium to evade the innate immune response and promotes survival within macrophages (Kawasaki et al., 2012; Petrone et al., 2014). More recently, a role of LpxR from EHEC Sakai strain was shown in the innate immune response evasion. Experiments with an EHEC O157:H7 IpxR mutant strain, reduced the lipid A deacylation and showed an increased inflammatory and phagocytic responses. These effects were attributed to the augmented NF-κB signaling and phosphorylated p38 mitogen protein kinase (MPK), both via TLR4 response. In contrast, LpxR-positive strains, able to modify the lipid A, were capable of attenuating these immune responses. This study also showed the prevalence of LpxR in other LEE positive pathotypes, as EPEC, and as we did in this study (FIG. 6). Furthermore, LpxR seems to be under the positive regulation of Ler and Pch-LEE-positive transcriptional regulators- and H—NS—global-negative regulator. Ler and H—NS seem to directly regulate the LpxR expression (as many of both LEE- and non-LEE-encoded genes). In addition, Pch and expression of LEE-virulence genes are involved also in the modulation of LPxR effect on lipid A, more directly by activating these virulence genes for colonization and in the phagocytic regulation response. In this regard, targeting a specific antibody response toward LpxR could potentially avoid the LPS modification and subsequent immune evasion. However, further studies are ongoing to characterize this protein and its role in EHEC pathogenesis and immune modulation in the host.

    [0313] The present studies on the EHEC O157:H7 genome combined with the GMMA antigen delivery system led us to identify new potential antigen candidates. In particular, one of them (MC001) was able to reduce intestinal bacterial colonization and to our knowledge this study was the first report describing a lipid A deacylase enzyme (LpxR) as an antigen candidate.

    REFERENCES

    [0314] Altschul, S. F., Madden, T. L., Schaffer, A. A., Zhang, J., Zhang, Z., Miller, W., et al. (1997). Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25(17), 3389-3402. [0315] Bartolini, E., Ianni, E., Frigimelica, E., Petracca, R., Galli, G., Berlanda Scorza, F., et al. (2013). Recombinant outer membrane vesicles carrying Chlamydia muridarum HtrA induce antibodies that neutralize chlamydial infection in vitro. J Extracell Vesicles 2. doi: 10.3402/jev.v2i0.20181. [0316] Benkert, P., Kunzli, M., and Schwede, T. (2009). QMEAN server for protein model quality estimation. Nucleic Acids Res 37 (Web Server issue), W510-514. doi: 10.1093/nar/gkp322. [0317] Berlanda Scorza, F., Colucci, A. M., Maggiore, L., Sanzone, S., Rossi, O., Ferlenghi, I., et al. (2012). High yield production process for Shigella outer membrane particles. PLoS One 7(6), e35616. doi: 10.1371/journal.pone.0035616. [0318] Berman, H. M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T. N., Weissig, H., et al. (2000). The Protein Data Bank. Nucleic Acids Res 28(1), 235-242. [0319] Bernadac, A., Gavioli, M., Lazzaroni, J. C., Raina, S., and Lloubes, R. (1998). Escherichia coli tol-pal mutants form outer membrane vesicles. J Bacterial 180(18), 4872-4878. [0320] Biasini, M., Bienert, S., Waterhouse, A., Arnold, K., Studer, G., Schmidt, T., et al. (2014). SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Res 42 (Web Server issue), W252-258. doi: 10.1093/nar/gku340. [0321] Croxen, M. A., and Finlay, B. B. (2010). Molecular mechanisms of Escherichia coli pathogenicity. Nat Rev Microbial 8(1), 26-38. doi: 10.1038/nrmicro2265. [0322] Croxen, M. A., Law, R. J., Scholz, R., Keeney, K. M., Wlodarska, M., and Finlay, B. B. (2013). Recent advances in understanding enteric pathogenic Escherichia coli. Clin Microbial Rev 26(4), 822-880. doi: 10.1128/CMR.00022-13. [0323] Daleke-Schermerhorn, M. H., Felix, T., Soprova, Z., Ten Hagen-Jongman, C. M., Vikstrom, D., Majlessi, L, et al. (2014). Decoration of outer membrane vesicles with multiple antigens by using an autotransporter approach. Appl Environ Microbial 80(18), 5854-5865. doi: 10.1128/AEM.01941-14. [0324] Datsenko, K. A., and Wanner, B. L. (2000). One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci USA 97(12), 6640-6645. doi: 10.1073/pnas.120163297. [0325] De Benedetto, G., Alfini, R., Cescutti, P., Caboni, M., Lanzilao, L, Necchi, F., et al. (2017). Characterization of O-antigen delivered by Generalized Modules for Membrane Antigens (GMMA) vaccine candidates against nontyphoidal Salmonella. Vaccine 35(3), 419-426. doi: 10.1016/j.vaccine.2016.11.089. [0326] Ebejer, J. P., Hill, J. R., Kelm, S., Shi, J., and Deane, C. M. (2013). Memoir: template-based structure prediction for membrane proteins. Nucleic Acids Res 41 (Web Server issue), W379-383. doi: 10.1093/nar/gkt331. [0327] Ellis, T. N., and Kuehn, M. J. (2010). Virulence and immunomodulatory roles of bacterial outer membrane vesicles. Microbial Mol Biol Rev 74(1), 81-94. doi: 10.1128/MMBR.00031-09. [0328] Fantappie, L, de Santis, M., Chiarot, E., Carboni, F., Bensi, G., Jousson, O., et al. (2014). Antibody-mediated immunity induced by engineered Escherichia coli OMVs carrying heterologous antigens in their lumen. J Extracell Vesicles 3. doi: 10.3402/jev.v3.24015. [0329] Garcia-Angulo, V. A., Kalita, A., Kalita, M., Lozano, L., and Torres, A. G. (2014). Comparative genomics and immunoinformatics approach for the identification of vaccine candidates for enterohemorrhagic Escherichia coli O157:H7. Infect Immun 82(5), 2016-2026. doi: 10.1128/IAI.01437-13. [0330] Garcia-Angulo, V. A., Kalita, A., and Torres, A. G. (2013). Advances in the development of enterohemorrhagic Escherichia coli vaccines using murine models of infection. Vaccine 31(32), 3229-3235. doi: 10.1016/j.vaccine.2013.05.013. [0331] Gerke, C., Colucci, A. M., Giannelli, C., Sanzone, S., Vitali, C. G., Sollai, L., et al. (2015). Production of a Shigella sonnei Vaccine Based on Generalized Modules for Membrane Antigens (GMMA), 1790GAHB. PLoS One 10(8), e0134478. doi: 10.1371/journal.pone.0134478. [0332] Goldwater, P. N., and Bettelheim, K. A. (2012). Treatment of enterohemorrhagic Escherichia coli (EHEC) infection and hemolytic uremic syndrome (HUS). BMC Med 10, 12. doi: 10.1186/1741-7015-10-12. [0333] Kaparakis-Liaskos, M., and Ferrero, R. L. (2015). Immune modulation by bacterial outer membrane vesicles. Nat Rev Immunol 15(6), 375-387. doi: 10.1038/nri3837. [0334] Kaper, J. B., Nataro, J. P., and Mobley, H. L (2004). Pathogenic Escherichia coli. Nat Rev Microbiol 2(2), 123-140. doi: 10.1038/nrmicro818. [0335] Kawasaki, K., Teramoto, M., Tatsui, R., and Amamoto, S. (2012). Lipid A 3′-O-deacylation by Salmonella outer membrane enzyme LpxR modulates the ability of lipid A to stimulate Toll-like receptor 4. Biochem Biophys Res Commun 428(3), 343-347. doi: 10.1016/j.bbrc.2012.10.054. [0336] Kearse, M., Moir, R., Wilson, A., Stones-Havas, S., Cheung, M., Sturrock, S., et al. (2012). Geneious Basic: an integrated and extendable desktop software platform for the organization and analysis of sequence data. Bioinformatics 28(12), 1647-1649. doi: 10.1093/bioinformatics/bts199. [0337] Klock, H. E., and Lesley, S. A. (2009). The Polymerase Incomplete Primer Extension (PIPE) method applied to high-throughput cloning and site-directed mutagenesis. Methods Mol Biol 498, 91-103. doi: 10.1007/978-1-59745-196-3_6. [0338] Krogh, A., Larsson, B., von Heijne, G., and Sonnhammer, E. L. (2001). Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J Mol Biol 305(3), 567-580. doi: 10.1006/jmbi.2000.4315. [0339] Landstorfer, R., Simon, S., Schober, S., Keim, D., Scherer, S., and Neuhaus, K. (2014). Comparison of strand-specific transcriptomes of enterohemorrhagic Escherichia coli O157:H7 EDL933 (EHEC) under eleven different environmental conditions including radish sprouts and cattle feces. BMC Genomics 15, 353. doi: 10.1186/1471-2164-15-353. [0340] MacLennan, C. A., and Saul, A. (2014). Vaccines against poverty. Proc Natl Acad Sci USA 111(34), 12307-12312. doi: 10.1073/pnas.1400473111. [0341] Maione, D., Margarit, I., Rinaudo, C. D., Masignani, V., Mora, M., Scarselli, M., et al. (2005). Identification of a universal Group B streptococcus vaccine by multiple genome screen. Science 309(5731), 148-150. doi: 10.1126/science.1109869. [0342] Mohawk, K. L, and O'Brien, A. D. (2011). Mouse models of Escherichia coli O157:H7 infection and shiga toxin injection. J Biomed Biotechnol 2011, 258185. doi: 10.1155/2011/258185. [0343] Mora, M., Donati, C., Medini, D., Covacci, A., and Rappuoli, R. (2006). Microbial genomes and vaccine design: refinements to the classical reverse vaccinology approach. Curr Opin Microbial 9(5), 532-536. doi: 10.1016/j.mib.2006.07.003. [0344] Mora, M., Veggi, D., Santini, L., Pizza, M., and Rappuoli, R. (2003). Reverse vaccinology. Drug Discov Today 8(10),459-464. [0345] Moriel, D. G., Bertoldi, I., Spagnuolo, A., Marchi, S., Rosini, R., Nesta, B., et al. (2010). Identification of protective and broadly conserved vaccine antigens from the genome of extraintestinal pathogenic Escherichia coli. Proc Natl Acad Sci USA 107(20), 9072-9077. doi: 10.1073/pnas.0915077107. [0346] Moriel, D. G., Rosini, R., Seib, K. L, Serino, L, Pizza, M., and Rappuoli, R. (2012). Escherichia coli: great diversity around a common core. MBio 3(3). doi: 10.1128/mBio.00118-12. [0347] Nesta, B., Valeri, M., Spagnuolo, A., Rosini, R., Mora, M., Donato, P., et al. (2014). SslE elicits functional antibodies that impair in vitro mucinase activity and in vivo colonization by both intestinal and extraintestinal Escherichia coli strains. PLoS Pathog 10(5), e1004124. doi: 10.1371/journal.ppat.1004124. [0348] Nielsen, H. (2017). Predicting Secretory Proteins with SignalP. Methods Mol Biol 1611, 59-73. doi: 10.1007/978-1-4939-7015-5_6. [0349] Nieves, W., Petersen, H., Judy, B. M., Blumentritt, C. A., Russell-Lodrigue, K., Roy, C. J., et al. (2014). A Burkholderia pseudomallei outer membrane vesicle vaccine provides protection against lethal sepsis. Clin Vaccine Immunol 21(5), 747-754. doi: 10.1128/CVI.00119-14. [0350] Perez-Cruz, C., Canas, M. A., Gimenez, R., Badia, J., Mercade, E., Baldoma, L, et al. (2016). Membrane Vesicles Released by a hypervesiculating Escherichia coli Nissle 1917 tolR Mutant Are Highly Heterogeneous and Show Reduced Capacity for Epithelial Cell Interaction and Entry. PLoS One 11(12), e0169186. doi: 10.1371/journal.pone.0169186. [0351] Perez-Cruz, C., Carrion, O., Delgado, L., Martinez, G., Lopez-Iglesias, C., and Mercade, E. (2013). New type of outer membrane vesicle produced by the Gram-negative bacterium Shewanella vesiculosa M7T: implications for DNA content. Appl Environ Microbial 79(6), 1874-1881. doi: 10.1128/AEM.03657-12. [0352] Petersen, H., Nieves, W., Russell-Lodrigue, K., Roy, C. J., and Morici, L. A. (2014). Evaluation of a Burkholderia pseudomallei Outer Membrane Vesicle Vaccine in Nonhuman Primates. Procedia Vaccinol 8, 38-42. doi: 10.1016/j.provac.2014.07.007. [0353] Petrone, B. L., Stringer, A. M., and Wade, J. T. (2014). Identification of HilD-regulated genes in Salmonella enterica serovar Typhimurium. J Bacteriol 196(5), 1094-1101. doi: 10.1128/JB.01449-13. [0354] Pizza, M., Scarlato, V., Masignani, V., Giuliani, M. M., Arico, B., Comanducci, M., et al. (2000). Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing. Science 287(5459), 1816-1820. [0355] Rappuoli, R. (2000). Reverse vaccinology. Curr Opin Microbial 3(5), 445-450. [0356] Rappuoli, R., Pizza, M., Del Giudice, G., and De Gregorio, E. (2014). Vaccines, new opportunities for a new society. Proc Natl Acad Sci USA 111(34), 12288-12293. doi: 10.1073/pnas.1402981111. [0357] Rivas, M., Chinen, I., and Guth, B. E. C. (2016). “Enterohemorrhagic (Shiga Toxin-Producing) Escherichia coli,” in Escherichia coli in the Americas, ed. A. G. Torres. (Cham: Springer International Publishing), 97-123. [0358] Rossi, O., Caboni, M., Negrea, A., Necchi, F., Alfini, R., Micoli, F., et al. (2016). Toll-Like Receptor Activation by Generalized Modules for Membrane Antigens from Lipid A Mutants of Salmonella enterica Serovars Typhimurium and Enteritidis. Clin Vaccine Immunol 23(4), 304-314. doi: 10.1128/CVI.00023-16. [0359] Rossi, O., Maggiore, L, Necchi, F., Koeberling, O., MacLennan, C. A., Saul, A., et al. (2015). Comparison of Colorimetric Assays with Quantitative Amino Acid Analysis for Protein Quantification of Generalized Modules for Membrane Antigens (GMMA). Molecular Biotechnology 57(1), 84-93. doi: 10.1007/s12033-014-9804-7. [0360] Roy, A., Kucukural, A., and Zhang, Y. (2010). I-TASSER: a unified platform for automated protein structure and function prediction. Nat Protoc 5(4), 725-738. doi: 10.1038/nprot.2010.5. [0361] Rutten, L., Mannie, J. P., Stead, C. M., Raetz, C. R., Reynolds, C. M., Bonvin, A. M., et al. (2009). Active-site architecture and catalytic mechanism of the lipid A deacylase LpxR of Salmonella typhimurium. Proc Natl Acad Sci USA 106(6), 1960-1964. doi: 10.1073/pnas.0813064106. [0362] Tapia, D., Ross, B. N., Kalita, A., Kalita, M., Hatcher, C. L, Muruato, L. A., et al. (2016). From In silico Protein Epitope Density Prediction to Testing Escherichia coli O157:H7 Vaccine Candidates in a Murine Model of Colonization. Front Cell Infect Microbiol 6, 94. doi: 10.3389/fcimb.2016.00094. [0363] Tarr, P. I., Gordon, C. A., and Chandler, W. L. (2005). Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet 365(9464), 1073-1086. doi: 10.1016/50140-6736(05)71144-2. [0364] Yu, N. Y., Wagner, J. R., Laird, M. R., Melli, G., Rey, S., Lo, R., et al. (2010). PSORTb 3.0: improved protein subcellular localization prediction with refined localization subcategories and predictive capabilities for all prokaryotes. Bioinformatics 26(13), 1608-1615. doi: 10.1093/bioinformatics/btq249.

    Numbered Embodiments

    [0365] 1. An isolated polypeptide comprising or consisting of: [0366] (a) an amino acid sequence selected from the group consisting of SEQ ID NOs: 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47 or 48; or [0367] (b) a variant and/or fragment of (a), for example: [0368] (i) a variant of (a); [0369] (ii) a fragment of (a); [0370] (iii) a variant of a fragment of (a). [0371] 2. The isolated polypeptide according to embodiment 1, wherein (a) is selected from the group consisting of SEQ ID NOs: 25, 26 and 27. [0372] 3. The isolated polypeptide according to any preceding embodiment, wherein (a) is SEQ ID NO: 25. [0373] 4. The isolated polypeptide according to any preceding embodiment, wherein (b) exhibits at least 60% sequence identity to an amino acid sequence listed in (a), for example, at least 61%,62%, 63%, 64%,65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99.5% sequence identity to an amino acid sequence listed in (a); [0374] (i) wherein the at least 60% sequence identity is exhibited over at least 60% of the amino acid sequence listed in (a), for example, a contiguous amino acid sequence spanning at least 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the amino acid sequence listed in (a); or [0375] (ii) wherein the at least 60% sequence identity is exhibited over at least 10 contiguous amino acids of the amino acid sequence listed in (a), for example, at least 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 1500, 2000, 2500, 2600, 2601, 2602, 2603, 2604, 2605, 2606, 2607, 2608, 2609, 2610, 2611, 2612, 2613, 2614, 2615, 2616, 2617, 2618 or 2619 contiguous amino acids of the amino acid sequence listed in (a). [0376] 5. The isolated polypeptide according to any preceding embodiment, wherein the polypeptide comprises or consists of a fragment comprising at least 10 contiguous amino acids, for example, at least 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233 contiguous amino acids, and/or, where present, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 1500, 2000, 2500 or 2600 contiguous amino acids. [0377] 6. The isolated polypeptide according to any preceding embodiment, wherein the polypeptide comprises or consists of a fragment wherein 1, or at least, 1 amino acid, is truncated from the N-terminus with respect to an amino acid sequence listed in (a), for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300 amino acids are truncated from the N-terminus with respect to the amino acid sequence listed in (a). [0378] 7. The isolated polypeptide according to any preceding embodiment, wherein the polypeptide comprises or consists of a fragment wherein 1, or at least 1 amino acid, is truncated from the C-terminus with respect to the reference sequence, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300 amino acids are truncated from the C-terminus with respect to the reference sequence. [0379] 8. The isolated polypeptide according to any preceding embodiment, wherein the polypeptide is fused to one or more additional polypeptide, for example: [0380] (a) N-terminal fusion; [0381] (b) C-terminal fusion; or [0382] (c) N-terminal and C-terminal fusion. [0383] 9. The isolated polypeptide according to any preceding embodiment, wherein the polypeptide is conjugated to one or more additional moiety, for example: [0384] (a) one or more lipid (to form a lipoprotein); [0385] (b) one or more saccharide or polysaccharide (to form a glycoprotein); [0386] (c) one or more phosphate group (to form a phosphoprotein); [0387] (d) one or more heme group (to form a hemoprotein); [0388] (e) one or more the flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN) (to form a flavoprotein); and [0389] (f) one or more metal ion cofactor (to form a metalloprotein). [0390] 10. The isolated polypeptide according to any preceding embodiment, wherein the polypeptide is substantially purified. [0391] 11. The isolated polypeptide according to any preceding embodiment, wherein the polypeptide is not naturally occurring. [0392] 12. The isolated polypeptide according to any preceding embodiment, wherein the polypeptide is recombinant. [0393] 13. The isolated polypeptide according to embodiment 1 wherein the polypeptide is a fragment, variant, fusion and/or derivative capable of inducing a specific immune response to an amino acid sequence listed in (a). [0394] 14. The isolated polypeptide according to embodiment 1 wherein the polypeptide is a fragment, variant, fusion and/or derivative capable of inducing an immune response to an amino acid sequence listed in (a). [0395] 15. The isolated polypeptide according to embodiment 2, wherein the immune response is an immune activating response. [0396] 16. The isolated polypeptide according to embodiment 2, wherein the immune response is a protective immune response. [0397] 17. The isolated polypeptide according to embodiment 3, wherein the polypeptide is capable of eliciting an in vitro protective immune response. [0398] 18. The isolated polypeptide according to embodiment 3, wherein the polypeptide is capable of eliciting an in vivo protective immune response. [0399] 19. The isolated polypeptide according to embodiment 5, wherein the polypeptide is capable of eliciting an in vivo protective immune response in a mammal. [0400] 20. The isolated polypeptide according to embodiment 6, wherein the mammal is selected from the group consisting of armadillo (dasypus novemcinctus), baboon (Papio anubis; Papio cynocephalus); camel (Camelus bactrianus, Camelus dromedarius, Camelus ferus) cat (Felis catus), dog (Canis lupus familiaris), horse (Equus ferus caballus), ferret (Mustela putorius furo), goat (Capra aegagrus hircus), guinea pig (Cavia porrellus), golden hamster (Mesocricetus auratus), kangeroo (Macropus rufus), llama (Lama glama), mouse (Mus musculus), pig (Sus scrofa domesticus), rabbit (Oryctolagus cuniculus), rat (Rattus norvegicus), rhesus macaque (Macaca mulatta), sheep (Ovis aries), non-human primate, and human (Homo sapiens). [0401] 21. The isolated polypeptide according to embodiment 18, wherein the protective immune response is protective against a disease or condition caused, wholly or in part, by an organism selected from the group consisting of: bacteria, Gram negative bacteria; proteobacteria, enterobacteriales, enterobacteriaceae (for example, Salmonella, Escherichia [E. alberti, E. coli, E. fergusonii, E. hermannii, E. marmotae, and E. vulneris], Yersinia, Klebsiella, Proteus, Enterobacter, Serratia, and Citrobacter). [0402] 22. The isolated polypeptide according to embodiment 21, wherein disease or condition caused, wholly or in part, by Escherichia coli, for example, extraintestinal pathogenic E. coli(ExPEC), or intestinal pathogenic E. coli (InPEC). [0403] 23. The isolated polypeptide according to embodiment 22, wherein the Escherichia coli is from a pathotype selected from the group consisting of: (i) enteropathogenic E. coli (EPEC); (ii) enterohemorrhagic E. coli (EHEC); (iii) enterotoxigenic E. coli (ETEC); (iv) enteroaggregative E. coli (EAEC); (v) diffusely adherent E. coli (DAEC); (vi) enteroinvasive E. coll (EIEC); (vii) uropathogenic E. coli (UPEC); (viii) neonatal meningitis E. coli (NMEC); (ix) Shiga Toxin (Stx) producing enteroaggregative E. coli(STEAEC); (x) adherent Invasive E. coli (AIEC); (xi) amoxicillin-resistant E. coli (AREC); (xii) asymptomatic bacteriuria E. coli (ABU); (xiii) Avian pathogenic E. coli (APEC). [0404] 24. The isolated polypeptide according to embodiment 22 or 23, wherein the Escherichia coli is an enterohaemorrhagic E. coli (EHEC) selected from the group consisting of: O157:H7 e.g., EHEC O157:H7 EDL933 strain; EHEC O157:H7 Sakai stain; EHEC 026:H11 (e.g., strain 11368); EHEC 0103:H2 (e.g., strain 12009); and EHEC O111:H− (e.g., strain 11128). [0405] 25. The isolated polypeptide according to embodiment 22 or 23, wherein the Escherichia coli is an enteropathogenic E. coli (EPEC) selected from the group consisting of: 055:H7 (e.g., CB9615); and 0127:H6 (e.g., strain E2348/69). [0406] 26. The isolated polypeptide according to embodiment 22 or 23, wherein the Escherichia coli is an enterotoxigenic E. coli(ETEC) selected from the group consisting of: H10407; E24377A; and Porcine ETEC. [0407] 27. The isolated polypeptide according to embodiment 22 or 23, wherein the Escherichia coli is an adherent Invasive E. coli (AIEC) selected from the group consisting of: LF82; 083:H1 NR G857C; and UM146. [0408] 28. The isolated polypeptide according to embodiment 22 or 23, wherein the Escherichia coli is an enteroaggregative E. coli (EAEC) selected from the group consisting of: 042, and 55989. [0409] 29. The isolated polypeptide according to embodiment 22 or 23, wherein the Escherichia coli is a neonatal meningitis E. coli (NMEC) selected from the group consisting of: 07:K1 CE10, 588, and 1H E3034. [0410] 30. The isolated polypeptide according to embodiment 22 or 23, wherein the Escherichia coli is an uropathogenic E. coli (UPEC) selected from the group consisting of: UMN026, CLONEDi14; CLONE Di2; CFT073; IA139; 536; NA114; and UTI89. [0411] 31. The isolated polypeptide according to embodiment 22 or 23, wherein the Escherichia coli is AREC SMS-3-5; APEC 01; or ABU 83972. [0412] 32. The isolated polypeptide according to embodiment 22, wherein the Escherichia coli is a strain with a K antigen selected from the group consisting of K1, K2a/ac, K3, K4, K5, K6, K7 (=K56), K8, K9 (=O104), K10, K11, K12 (K82), K13 (=K20 and =K23), K14, K15, K16, K18a, K18ab (=K22), K19,K24, K26, K27, K28, K29, K130, K31, K34, K37, K39, K40, K41,K42, K43, K44, K45, K46, K47, K49 (046), K50, K51, K52, K53, K54 (=K96), K55, K74, K84, K85ab/ac (=O141), K87 (=O32), K92, K93, K95, K97, K98, K100, K101, K102, K103, KX104, KX105, and KX106). [0413] 33. The isolated polypeptide according to embodiment 22 or 32, wherein the Escherichia coli is a strain with an O antigen selected from the group consisting of O1 A, O1 A1, O1 B, O1 C, O2, O3, O4, O4, O5 ab, O5 ac, O6, O6, O6, O7, O8, O9, O9 a, O10, O11, O12, O13, O15, O16, O16, O16, O17, O18 A, O18 A1, O18 A1A2, O18 ab, O18 ac, O18 B, O18 B1, O19 ab, O20 ab, O20 ac, O21, O22, O23 A, O24, O25, O26, O27, O28 ab, O28 ac, O29, O30, O32, O33, O34, O35, O36, O37, O38, O39, O40, O41, O42, O43, O44, O45, O45 rel, O46, O48, O49, O50, O51, O52, O53, O54, O55, O55, O56, O58, O59, O60, O61, O62, O63, O64, O65, O66, O68, O69, O70, O71, O73, O73 ab, O74, O75, O76, O77, O78, O79, O80, O81, O82, O83, O84, O85, O86, O86, O86, O87, O88, O89, O90, O91, O92, O95, O96, O97, O98, O99, O100, O101, O102, O103, O104, O105, O106, O107, O108, O109, O110, O111, O112 ab, O112 ac, O113, O114, O115, O116, O117, O118, O119, O120, O121, O123, O124, O125ab, O125ac, O126, O126, O127, O128ab, O128 ab, O128 ac, O129, O130, O131, O132, O133, O134, O135, O136, O137, O138, O139, O140, O141, O142, O143, O144, O145, O146, O147, O148, O149, O150, O151, O152, O153, O154, O155, O156, O157, O158 ab, O158 ac, O159, O160, O161, O163, O164, O165, O166, O167, O168, O169, O170, O171, O172, O173, O174 ab, O174 ac, O175, O176, O177, O178, O179, O180, O181, O182, O183, O184, O185, O186 and O187. [0414] 34. The isolated polypeptide according to embodiment 22, 32 or 33, wherein the Escherichia coli is a strain with a H antigen selected from the group consisting of: H1, H2, H3, H4, H5, H6, H7, H8, H9, H10 (=H50), H11, H12, H13, H14, H15, H16, H17, H18, H19, H20, H21, H22, H23, H24, H25, H26, H27, H28, H29, H30, H31, H32, H33, H34, H35, H36, H37, H38, H39, H40, H41, H42, H43, H44, H45, H46, H47, H48, H49, H50 (=H10), H51, H52, H53, H54, H55 and H56. [0415] 35. The isolated polypeptide according to any one of embodiments 16-20, wherein the protective immune response is protective against a disease or condition selected from the group consisting of: gastroenteritis; haemolytic uremic syndrome (HUS), urinary tract infection; neonatal meningitis; haemorrhagic colitis; and Crohn's disease. [0416] 36. The isolated polypeptide according to any preceding embodiment, wherein the protective immune response is an immune response that results in increased seral cytokine levels; for example, cytokines selected from the group consisting of IL-1α, IL-1β, IL-IRA, IL-18, IL-2, IL-4, IL-7, IL-9, IL-13, IL-15, IL-3, IL-5, GM-CSF, IL-6, IL-11, G-C5F, IL-12, LIF, O5M, IL-10, IL-20, IL-14, IL-16, IL-17, IFN-α, IFN-β, IFN-γ, CD154, LT-β, TNF-α, TNF-β, 4-1BBL, APRIL, CD70, CD153, CD178, GITRL, LIGHT, OX40L, TALL-1, TRAIL, TWEAK, TRANCE, TGF-β1, TGF-β2, TGF-β3, Epo, Tpo, Flt-3L, SCF, M-CSF and MSP. [0417] 37. The isolated polypeptide according to any preceding embodiment, wherein the protective immune response is an immune response is an immune response that results in bactericidal activity and/or opsonophagocytosis. [0418] 38. An isolated nucleic acid molecule comprising or consisting of: [0419] (A) a nucleic acid sequence selected from the group consisting of selected from the group consisting of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24; or [0420] (B) a fragment, variant and/or fusion of (A). [0421] 39. The isolated nucleic acid according to embodiment 38, wherein (A) is selected from the group consisting of SEQ ID NOs: 1, 2 and 3. [0422] 40. The isolated nucleic acid according to embodiment 38 or 39, wherein (A) is SEQ ID NO: 1. [0423] 41. The isolated nucleic acid according to embodiment 38, wherein (B) exhibits at least 60% sequence identity to a nucleic acid sequence listed in (A), for example, at least 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleic acid sequence listed in (a); and [0424] (I) wherein the at least 60% sequence identity is exhibited over at least 60% of the nucleic acid sequence listed in (a), for example, a contiguous amino acid sequence spanning at least 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the nucleic acid sequence listed in (A); or [0425] (II) wherein the at least 60% sequence identity is exhibited over at least 30 contiguous nucleic acids of the nucleic acid sequence listed in (A), for example, at least 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 350, 400, 450, 500, 550,600,650, 700, 750, 800, 850,900, 950, 1000, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000, 5500,6000,6500,7000, or 7500 contiguous amino acids of the nucleic acid sequence listed in (A). [0426] 42. The isolated nucleic acid according to any one of embodiments 38-41, wherein the nucleic acid encodes a polypeptide according to embodiments 1-37. [0427] 43. A vector comprising a nucleic acid molecule defined in any one of embodiments 38-42. [0428] 44. A host cell comprising a nucleic acid molecule defined in any one of embodiments 38-42 or a vector as defined in embodiment 43. [0429] 45. A method for producing a polypeptide according to any one of embodiments 1-37: comprising or consisting of the steps of culturing a population of host cells according to embodiment 44 under conditions in which the peptide is expressed, and isolating the peptide therefrom. [0430] 46. A vesicle comprising one or more polypeptide defined in any one of embodiments 1-37. [0431] 47. The vesicle according to embodiment 46, wherein the vesicle is derived from the membrane of a cell, for example, a Gram positive bacteria membrane vesicle or a Gram negative bacteria outer membrane vesicle (OMV). [0432] 48. The vesicle according to embodiment 46, wherein the vesicle is a Gram negative bacteria outer membrane vesicle (OMV) of a bacterium defined in any one of embodiments 21-34. [0433] 49. The vesicle according to any one of embodiments 46-48, wherein the polypeptide is: [0434] (a) homologous to the cell; or [0435] (b) heterologous to the cell. [0436] 50. The vesicle according to any one of embodiments 45-49, wherein the polypeptide is: [0437] (a) located in the lumen of the vesicle (for example, where the vesicle is a cell, in the cytoplasm); [0438] (b) located in the/a inter-membrane space of the vesicle (for example, where the vesicle is a cell, the periplasm); and/or [0439] (c) located on the outer surface of the outer membrane (for example, where the vesicle is a cell, the outer membrane). [0440] 51. The vesicle according to any one of embodiments 46-50, wherein the polypeptide expressed by the cell. [0441] 52. The vesicle according to any one of embodiments 46-50, wherein the polypeptide is chemically conjugated to the vesicle (for example, to a lipid, protein or polysaccharide component of the vesicle membrane). [0442] 53. A binding moiety capable of specifically binding to one or more polypeptide defined in any one of embodiments 1-37. [0443] 54. The binding moiety according to embodiment 53, wherein the binding moiety is selected from the group consisting of: antibodies; antigen-binding fragments; and antibody mimetics. [0444] 55. The binding moiety according to embodiment 53 or 54, wherein the binding moiety is an antibody. [0445] 56. The binding moiety according to embodiment 55, wherein the antibody is polyclonal or monoclonal. [0446] 57. The binding moiety according to embodiment 55, wherein the binding moiety is an antigen-binding fragment selected from the group consisting of: Fab (fragment antigen binding); F(ab′)2; Fab′; scFv (single chain variable fragment); di-scFv; sdAb (single domain antibody/domain antibody); trifunctional antibody; chemically-linked F(ab′).sub.2; and BiTE (bi-specific T-cell engager). [0447] 58. The binding moiety according to embodiment 57, wherein the antibody or antigen binding fragment thereof is an antigen binding fragment selected from the group consisting of affibodies molecules; affilins; affimers; affitins; alphabodies; anticalins; avimers; DARPins; fynomers; kunitz domain peptides; monobodies and nanoCLAMPs. [0448] 59. A pharmaceutical composition comprising a polypeptide defined in any one of embodiments 1-37, a nucleic acid molecule defined in any one of embodiments 38-42, a vector as defined in embodiment 43, a host cell as defined in embodiment 46, a vesicle as defined in any one of embodiments 46-52 and/or a binding moiety as defined in any one of embodiments 53-58. [0449] 60. A kit comprising or consisting of a polypeptide defined in any one of embodiments 1-37, a nucleic acid molecule defined in any one of embodiments 38-42, a vector as defined in embodiment 43, a host cell as defined in embodiment 44, a vesicle as defined in any one of embodiments 46-52, a binding moiety as defined in any one of embodiments 53-58 and/or a pharmaceutical composition as defined in embodiment 59; and (optionally) instructions for use. [0450] 61. A polypeptide defined in any one of embodiments 1-37, a nucleic acid molecule defined in any one of embodiments 38-42, a vector as defined in embodiment 43, a host cell as defined in embodiment 44, a vesicle as defined in any one of embodiments 46-52, a binding moiety as defined in any one of embodiments 53-58 and/or a pharmaceutical composition as defined in embodiment 59, for use in medicine. [0451] 62. A polypeptide defined in any one of embodiments 1-37, a nucleic acid molecule defined in any one of embodiments 38-42, a vector as defined in embodiment 43, a host cell as defined in embodiment 44, a vesicle as defined in any one of embodiments 46-52, a binding moiety as defined in any one of embodiments 53-58 and/or a pharmaceutical composition as defined in embodiment 59, for use in preventing or treating bacterial infection and/or symptoms thereof. [0452] 63. The polypeptide, nucleic acid molecule, vector, vesicle, host cell, binding moiety and/or pharmaceutical composition for use according to embodiment 62, wherein the bacterial infection is, wholly or in part, infection with one or more bacterium defined in any one of embodiments 21-34. [0453] 64. The polypeptide, nucleic acid molecule, vector, vesicle, host cell, binding moiety and/or pharmaceutical composition for use according to embodiment 63, wherein the use comprises the consecutive or concurrent use of: [0454] (a) a polypeptide defined in embodiments 1-37; [0455] (b) a nucleic acid molecule defined in embodiments 38-42; [0456] (c) a vector as defined in embodiment 43; [0457] (d) a vesicle as defined in any one of embodiments 46-52; [0458] (e) a host cell as defined in embodiment 44; [0459] (f) a binding moiety as defined in any one of embodiments 53-58; and/or [0460] (g) a pharmaceutical composition as defined in embodiment 59. [0461] 65. The polypeptide, nucleic acid molecule, vector, vesicle, host cell, binding moiety and/or pharmaceutical composition for use according to embodiment 64, wherein the use comprises the consecutive or concurrent use of a binding moiety as defined in any one of embodiments 53-58 with: [0462] (a) a nucleic acid molecule defined in any one of embodiments 37-42 and/or a vector as defined in embodiment 43; and/or [0463] (b) a binding moiety as defined in any one of embodiments 53-58 and/or a vesicle as defined in any one of embodiments 46-52. [0464] 66. The use of polypeptide defined in any one of embodiments 1-37, a nucleic acid molecule defined in any one of embodiments 38-42, a vector as defined in embodiment 43, a host cell as defined in embodiment 44, a vesicle as defined in any one of embodiments 46-52, a binding moiety as defined in any one of embodiments 53-58 and/or a pharmaceutical composition as defined in embodiment 59, in preventing or treating bacterial infection and/or symptoms thereof, for example, wherein the bacterial infection is, wholly or in part, infection with one or more bacterium defined in any one of embodiments 21-34. [0465] 67. The use of polypeptide defined in any one of embodiments 1-37, a nucleic acid molecule defined in any one of embodiments 38-42, a vector as defined in embodiment 43, a host cell as defined in embodiment 44, a vesicle as defined in any one of embodiments 46-52, a binding moiety as defined in any one of embodiments 53-58 and/or a pharmaceutical composition as defined in embodiment 59, in the manufacture of a medicament for preventing or treating bacterial infection and/or symptoms thereof, for example, wherein the bacterial infection is, wholly or in part, infection with one or more bacterium defined in any one of embodiments 21-34. [0466] 68. A method for preventing or treating bacterial infection and/or symptoms thereof comprising or consisting of administering to a subject an effective amount of a polypeptide defined in any one of embodiments 1-37, a nucleic acid molecule defined in any one of embodiments 38-42, a vector as defined in embodiment 43, a host cell as defined in embodiment 44, a vesicle as defined in any one of embodiments 46-52, a binding moiety as defined in any one of embodiments 53-58 and/or a pharmaceutical composition as defined in embodiment 59, for example, wherein the bacterial infection is, wholly or in part, infection with one or more bacterium defined in any one of embodiments 21-34. [0467] 69. The use of a nucleic acid molecule defined in any one of embodiments 38-42, or a binding moiety as defined in any one of embodiments 53-58, for detecting the presence of bacteria, for example, wherein the bacteria are one or more bacterium defined in any one of embodiments 21-34. [0468] 70. The use according to embodiment 69, wherein the detection is in vitro and/or in vivo. [0469] 71. A polypeptide, nucleic acid molecule, vector, vesicle, host cell, binding moiety, pharmaceutical composition, use or method as described in specification and figures herein.

    TABLE-US-00003 TABLE S1 Antigen candidates selected by Psort analysis Length PSORT PSORT Mod Protein ID Functional annotation (bp) Local..sup.1 score HMM.sup.2 AIG68144.1 Ferric siderophore transport system, 720 U 2 1 periplasmicbinding protein TonB CDS AIG70214.1 Type III secretion outermembrane pore 1704 OM 10 1 forming protein (YscC, MxiD, HrcC, InvG) CDS AIG71811.1 adherence and invasion outermembrane 5037 OM 9.95 0 protein (Inv, enhances Peyer's patches colonization) CDS AIG66227.1 Putative outer membrane protein CDS 2451 OM 10 0 AIG66265.1 Outer membrane protein Imp, required for 2322 OM 10 0 envelope biogenesis CDS AIG66267.1 hypothetical protein CDS 753 U 2 0 AIG66308.1 Secretion monitor precursor CDS 588 U 6.49 1 AIG66347.1 Fimbrial protein Yad like protein CDS 1110 U 2 1 AIG66348.1 Fimbrial protein YadK CDS 591 U 2 0 AIG66349.1 Fimbrial protein YadL CDS 606 U 2.5 1 AIG66351.1 Outer membrane usher protein HtrE CDS 2601 OM 10 0 AIG66353.1 Fimbrial protein YadN CDS 597 Ex 9.65 1 AIG66363.1 Ferric hydroxamate outer membrane 2244 OM 10 0 receptor FhuA CDS AIG66390.1 Outer membrane protein assembly factor 2433 OM 10 1 YaeT precursor CDS AIG66406.1 Copper homeostasis protein CutF precursor 711 OM 9.92 0 CDS AIG66407.1 putative lipoprotein yaeF precursor CDS 825 U 2.5 0 AIG66409.1 hypothetical protein CDS 708 U 2 0 AIG66417.1 hypothetical protein CDS 801 U 2 0 AIG66424.1 putative aminopeptidase CDS 801 U 2.5 1 AIG66428.1 hypothetical protein CDS 1410 U 2 1 AIG66446.1 core protein CDS 4215 U 2 0 AIG66447.1 hypothetical protein CDS 612 U 2 1 AIG66450.1 core protein CDS 1761 Ex 9.52 0 AIG66460.1 putative exported protein CDS 741 U 2.5 1 AIG66464.1 putative lipoprotein yafL precursor CDS 774 U 4.9 1 AIG66480.1 Outer membrane pore protein E precursor 1056 OM 10 1 CDS AIG66490.1 putative tail fiber protein CDS 795 U 2 0 AIG66511.1 Zinc binding domain protein CDS 2334 U 2 0 AIG66518.1 hypothetical protein CDS 1137 U 2.5 1 AIG66526.1 CFA/I fimbrial chaperone CDS 711 U 2.5 1 AIG66527.1 CFA/I fimbrial minor adhesin CDS 1644 Ex 9.64 1 AIG66528.1 CFA/I fimbrial subunit C usher protein CDS 2526 U 4.69 2 AIG66528.1 Putative adhesin CDS 4254 OM 10 0 AIG66545.1 AidA-I adhesin-like protein CDS 4050 U 5.87 0 AIG66568.1 hypothetical protein CDS 864 U 2 0 AIG66574.1 Putative flagellin structural protein CDS 2943 OM 10 0 AIG66636.1 hypothetical protein CDS 624 U 2 0 AIG66640.1 putative lipoprotein CDS 1095 U 2.5 0 AIG66656.1 Protein YkiA CDS 2166 U 2 0 AIG66683.1 Nucleoside-specific channel-forming 885 OM 10 0 protein Tsx precursor CDS AIG66684.1 putative lipoprotein yajI CDS 540 U 2 0 AIG66769.1 Large repetitive protein CDS 4386 U 6.04 1 AIG66781.1 Putative stomatin/prohibitin-family 918 U 2 U membrane protease subunit YbbK AIG66819.1 Oligopeptide ABC transporter, periplasmic 1701 U 2 0 oligopeptide-binding protein OppA CDS AIG66819.1 Outer membrane usher protein SfmD CDS 2610 OM 10 2 AIG66854.1 Agglutination protein CDS 1356 OM 10 1 AIG66854.1 TonB-dependent receptor CDS 2241 OM 10 0 AIG66909.1 Rare lipoprotein A precursor CDS 1089 Ex 9.65 0 AIG66920.1 hypothetical protein CDS 588 Ex 9.71 0 AIG66922.1 hypothetical protein CDS 708 U 2 0 AIG66972.1 core protein CDS 4200 U 2 0 AIG66973.1 orf, hypothetical protein CDS 543 U 2 0 AIG66984.1 hypothetical protein CDS 1062 U 2.5 0 AIG66987.1 putative fimbrial-like protein ygiL precursor 567 Ex 9.72 0 CDS AIG67020.1 TolA protein CDS 1185 U 2 2 AIG67060.1 Putative outer membrane protein CDS 960 U 2.5 1 AIG67099.1 Biotin synthesis protein BioC CDS 756 U 2 0 AIG67129.1 Ferrichrome-iron receptor CDS 2283 OM 10 0 AIG67212.1 Virulence factor VirK CDS 993 U 2 0 AIG67245.1 Urease accessory protein UreF CDS 675 U 2 0 AIG67247.1 Per-activated serine protease autotransporter 126 Ex 9.71 U enterotoxin EspC AIG67280.1 Colicin I receptor precursor CDS 2010 OM 10 0 AIG67308.1 putative hemolysin activator protein CDS 1065 OM 8.86 1 AIG67367.1 Putative metalloprotease yggG 789 U 2 U AIG67384.1 exported protein CDS 549 U 2.5 1 AIG67387.1 Outer membrane protein F precursor CDS 1089 OM 10 1 AIG67397.1 type 1 fimbriae major subunit FimA CDS 540 Ex 10 0 AIG67400.1 type 1 fimbriae anchoring protein FimD 1893 OM 10 0 CDS AIG67407.1 hypothetical protein CDS 543 U 2 0 AIG67412.1 Paraquat-inducible protein B CDS 1641 U 2 1 AIG67413.1 Paraquat-inducible protein B CDS 564 U 2 0 AIG67419.1 Outer membrane protein A precursor CDS 1065 OM 10 0 AIG67426.1 UPF0319 protein YccT precursor CDS 663 U 2.5 1 AIG67448.1 hypothetical protein CDS 558 U 2 0 AIG67453.1 hypothetical protein CDS 774 U 2 0 AIG67464.1 Hypothetical protein CDS 1851 U 2 0 AIG67503.1 hypothetical protein CDS 753 Ex 9.71 0 AIG67516.1 Putative polysaccharide export protein 1140 OM 9.92 1 YccZ precursor CDS AIG67517.1 Putative outer membrane lipoprotein YmcA 2097 OM 9.52 0 CDS AIG67577.1 Shiga-like toxin II subunit A precursor CDS 960 U 2.5 1 AIG67607.1 hypothetical protein CDS 618 U 2 0 AIG67611.1 hypothetical protein CDS 657 U 2 0 AIG67633.1 hypothetical protein CDS 1344 Ex 9.64 0 AIG67644.1 Biofilm PGA synthesis deacetylase PgaB 2019 U 2 1 CDS AIG67645.1 Biofilm PGA outer membrane secretin 2424 U 2.5 0 PgaA CDS AIG67652.1 Putative exported protein precursor CDS 1086 U 2 0 AIG67653.1 outer membrane fimbrial usher protein CDS 2523 OM 10 0 AIG67658.1 Hemolysin CDS 3813 OM 9.95 0 AIG67671.1 hypothetical protein CDS 789 U 2 0 AIG67672.1 hypothetical protein CDS 1389 U 2 0 AIG67699.1 Per-activated serine protease autotransporter 126 Ex 9.71 U enterotoxin EspC AIG67732.1 TonB-dependent receptor CDS 2010 OM 10 0 AIG67760.1 putative hemolysin activator protein CDS 1065 OM 8.86 1 AIG67820.1 Protein yceI precursor CDS 576 U 2.5 1 AIG67827.1 Putative lipoprotein yceB precursor CDS 561 U 2 0 AIG67831.1 Protein of unknown function YceH CDS 648 U 2 0 AIG67832.1 Virulence factor MviM CDS 924 U 2 0 AIG67840.1 Flagellar basal-body rod modification 696 Ex 10 0 protein FlgD CDS AIG67841.1 Flagellar hook protein FlgE CDS 1206 Ex 10 0 AIG67843.1 Flagellar basal-body rod protein FlgG CDS 783 Ex 10 0 AIG67844.1 Flagellar L-ring protein FlgH CDS 699 OM 10 1 AIG67847.1 Flagellar hook-associated protein FlgK CDS 1644 Ex 9.96 0 AIG67848.1 Flagellar hook-associated protein FlgL CDS 954 Ex 10 0 AIG67862.1 YceG like protein CDS 1023 U 6.49 1 AIG67867.1 Putative OMR family iron-siderophore 2190 OM 10 0 receptor precursor CDS AIG67871.1 Lipoprotein YcfM, part of a salvage 642 U 2 0 pathway of unknown substrate CDS AIG67876.1 Putative exported protein CDS 540 U 2.5 1 AIG67905.1 hypothetical protein CDS 588 U 2 0 AIG67914.1 Hypothetical protein CDS 1938 U 2 0 AIG67929.1 hypothetical protein CDS 1938 U 2 0 AIG67963.1 hypothetical protein CDS 744 U 2 0 AIG68016.1 hypothetical protein CDS 1602 U 2 0 AIG68033.1 Attachment invasion locus protein precursor 600 OM 10 1 CDS AIG68048.1 Protease VII (Omptin) precursor CDS 954 OM 10 0 AIG68053.1 Pertactin precursor CDS 705 U 7 0 AIG68064.1 Hemolysin E, chromosomal CDS 1056 Ex 10 0 AIG68081.1 Putative TonB dependent outer membrane 1971 OM 10 0 receptor CDS AIG68093.1 Putative adhesion and penetration protein 1644 Ex 9.65 0 CDS AIG68114.1 Invasin CDS 1431 OM 10 0 AIG68125.1 UPF0028 protein YchK CDS 945 Ex 8.89 0 AIG68148.1 Outer membrane protein W precursor CDS 639 OM 10 0 AIG68163.1 hypothetical protein CDS 582 U 2 0 AIG68165.1 Putative intestinal colonization factor 747 U 2 0 encoded by prophage CP-933O CDS AIG68173.1 Hypothetical protein CDS 1854 U 2 0 AIG68183.1 hypothetical protein CDS 1938 U 2 0 AIG68190.1 putative major tail subunit CDS 786 Ex 9.64 0 AIG68238.1 Hypothetical protein CDS 1851 U 2 0 AIG68271.1 Attachment invasion locus protein precursor 600 OM 10 1 CDS AIG68309.1 Autoinducer 2 (AI-2) aldolase LsrF CDS 876 U 2 0 AIG68316.1 hypothetical protein CDS 3894 U 5.87 0 AIG68317.1 hypothetical protein CDS 1401 OM 9.83 0 AIG68320.1 type 1 fimbriae major subunit FimA CDS 564 Ex 10 1 AIG68322.1 type 1 fimbriae anchoring protein FimD 2223 OM 10 0 CDS AIG68325.1 mannose-specific adhesin FimH CDS 915 U 2 1 AIG68333.1 hypothetical protein CDS 2373 OM 9.49 0 AIG68337.1 redicted glycoside hydrolase CDS 1320 U 2 0 AIG68357.1 Outer membrane porin protein NmpC 1101 OM 10 1 precursor CDS AIG68359.1 hypothetical protein CDS 669 U 2 0 AIG68376.1 internalin, putative CDS 1260 U 2 0 AIG68383.1 hypothetical protein CDS 1062 U 2.5 0 AIG68385.1 core protein CDS 4203 U 5.48 0 AIG68385.1 putative tonB-dependent receptor yncD 2019 OM 10 0 precursor CDS AIG68406.1 putative membrane lipoprotein clustered 669 U 2 0 with tellurite resistance proteins TehA/TehB CDS AIG68433.1 putative BigA-like protein CDS 2460 U 6.26 0 AIG68444.1 Outer membrane protein N precursor CDS 753 OM 10 0 AIG68484.1 porin, autotransporter (AT) family CDS 3036 Ex 9.65 2 AIG68484.1 Hypothetical protein CDS 1854 U 2 0 AIG68547.1 Outer membrane protein G precursor CDS 906 OM 10 0 AIG68579.1 RND efflux system, outer membrane 1374 OM 9.98 0 lipoprotein CmeC CDS AIG68638.1 Attachment invasion locus protein precursor 600 OM 10 1 CDS AIG68679.1 Hypothetical protein CDS 1851 U 2 0 AIG68688.1 hypothetical protein CDS 585 U 2 0 AIG68723.1 Putative protease ydgD 822 U 2.5 U AIG68730.1 Protein ydgH precursor CDS 945 U 2.5 0 AIG68784.1 Putative lipoprotein CDS 816 U 6.49 0 AIG68794.1 putative enzyme CDS 1257 U 7 0 AIG68797.1 hypothetical protein CDS 813 U 2 0 AIG68812.1 Iron-sulfur cluster assembly protein SufB 1488 U 2 0 CDS AIG68838.1 hypothetical protein CDS 714 U 2 0 AIG68851.1 hypothetical protein CDS 1899 U 2 0 AIG68853.1 Putative outer membrane protein CDS 759 U 2.5 0 AIG68861.1 hypothetical protein CDS 768 U 2 0 AIG68883.1 Hypothetical protein YdjY CDS 678 U 2.5 0 AIG68886.1 ABC transporter, periplasmic substrate- 1167 U 2.5 0 binding protein YnjB CDS AIG68897.1 Protein ydjA CDS 552 U 2 1 AIG68899.1 putative lipoprotein CDS 711 U 2 1 AIG68918.1 MltA-interacting protein MipA CDS 747 OM 10 0 AIG68945.1 Starvation lipoprotein Slp-like protein CDS 582 OM 9.92 1 AIG68946.1 Inactive metal-dependent proteases like 696 U 2 U protein, putative molecular chaperone AIG68978.1 Paraquat-inducible protein B CDS 2640 U 2 2 AIG68989.1 Protease II 2061 U 5.41 U AIG69001.1 Cell wall endopeptidase, family M23/M37 1323 U 2 1 CDS AIG69007.1 hypothetical protein CDS 603 U 2 0 AIG69057.1 putative membrane protein CDS 651 U 2 1 AIG69095.1 Flagellar biosynthesis protein FliZ CDS 552 U 2 0 AIG69098.1 Flagellar biosynthesis protein FliC CDS 1758 Ex 9.96 0 AIG69099.1 Flagellar hook-associated protein FliD CDS 1398 Ex 10 0 AIG69108.1 invasion plasmid antigen CDS 1140 Ex 8.89 0 AIG69110.1 invasion plasmid antigen CDS 1140 Ex 8.89 0 AIG69118.1 Flagellar hook-length control protein FliK 1128 Ex 10 0 CDS AIG69140.1 Outer membrane protein N precursor CDS 645 OM 10 1 AIG69141.1 Outer membrane protein N precursor CDS 576 OM 10 0 AIG69149.1 putative zinc-binding lipoprotein ZinT CDS 651 U 2.5 0 AIG69153.1 hypothetical protein CDS 711 U 2 0 AIG69158.1 Attachment invasion locus protein precursor 600 OM 10 1 CDS AIG69189.1 Hypothetical protein CDS 1851 U 2 0 AIG69198.1 hypothetical protein CDS 564 U 2 0 AIG69216.1 adherence and invasion outermembrane 7863 OM 9.95 0 protein (Inv, enhances Peyer's patches colonization) CDS AIG69305.1 AsmA protein CDS 1854 U 2.5 1 AIG69312.1 Putative chaperonin CDS 1941 U 2 2 AIG69314.1 hypothetical protein CDS 660 U 2 0 AIG69346.1 Uncharacterized protein YehA precursor 1035 U 2 0 CDS AIG69347.1 Fimbriae usher protein StcC CDS 2481 OM 10 0 AIG69349.1 Putative fimbrial-like protein CDS 543 U 2.5 1 AIG69361.1 hypothetical protein CDS 1530 U 2 0 AIG69362.1 hypothetical protein CDS 732 U 2 0 AIG69377.1 Attachment invasion locus protein precursor 600 OM 10 1 CDS AIG69390.1 Minor tail protein Z CDS 624 U 2 0 AIG69393.1 Prophage Clp protease-like protein 1041 U U AIG69411.1 Shiga toxin A-chain precursor CDS 948 U 2.5 1 AIG69429.1 putative superinfection exclusion protein 555 U 2 2 CDS AIG69485.1 Colicin I receptor precursor CDS 1884 OM 10 0 AIG69508.1 Lipoprotein spr precursor CDS 567 U 2.5 0 AIG69510.1 ABC transporter, periplasmic substrate- 1815 U 6.58 0 binding protein CDS AIG69523.1 Putative ATP-binding component of a 2592 Ex 9.46 0 transport system CDS AIG69547.1 Outer membrane protein C precursor CDS 1104 OM 10 1 AIG69552.1 hypothetical protein CDS 777 U 2 0 AIG60553.1 Putative membrane protein CDS 4515 U 4.69 0 AIG60558.1 Type V secretory pathway, adhesin AidA 3705 OM 9.83 0 CDS AIG69581.1 Polymyxin resistance protein PmrG CDS 603 U 2.5 1 AIG69644.1 DedD protein CDS 663 U 2 1 AIG69664.1 Uncharacterized protein YadU in stf 843 U 2 0 fimbrial cluster CDS AIG69669.1 Fimbriae usher protein StfC CDS 2583 OM 10 0 AIG69676.1 Long-chain fatty acid transport protein CDS 1341 OM 10 0 AIG69679.1 Lipoprotein CDS 756 OM 9.92 2 AIG69706.1 hypothetical protein CDS 636 U 2.5 0 AIG69727.1 putative virulence protein CDS 1149 U 2 0 AIG60790.1 YpfJ protein, zinc metalloprotease 864 U 2 U superfamily AIG69792.1 Outer membrane protein NlpB, lipoprotein 1035 OM 9.93 0 component of the protein assembly complex (forms a complex with YaeT, YfiO, and YfgL) CDS AIG69809.1 Exported zinc metalloprotease YfgC 1464 U 2.5 U precursor AIG69829.1 Outer membrane protein YfgL, lipoprotein 1179 OM 9.92 0 component of the protein assembly complex (forms a complex with YaeT, YfiO, and NlpB) CDS AIG69833.1 putative membrane protein CDS 1014 U 2 1 AIG69842.1 Thiosulfate sulfurtransferase, rhodanese 846 U 5.41 1 CDS AIG69880.1 putative alpha helix protein CDS 636 U 2 0 AIG69913.1 hypothetical protein CDS 564 U 2 0 AIC69916.1 hypothetical protein CDS 732 U 2 0 AIC69918.1 putative component of the lipoprotein 738 OM 10 0 assembly complex (forms a complex with YaeT, YfgL, and NlpB) CDS AIG69931.1 Signal recognition particle, subunit Ffh 1362 U 5.6 0 SRP54 CDS AIG69958.1 Hypothetical protein CDS 1854 U 2 0 AIG69974.1 Pertactin precursor CDS 4308 U 5.87 0 AIG70043.1 Coenzyme F420 hydrogenase maturation 471 U U protease AIG70069.1 Lipoprotein NlpD CDS 1140 OM 9.93 0 AIC70199.1 Type III secretion bridge between inner and 735 OM 9.92 1 outermembrane lipoprotein (YscJ, HrcJ, EscJ, PscJ) CDS AIG70202.1 Type III secretion protein EprH CDS 735 U 2 1 AIG70217.1 Uncharacterized protein YgeP CDS 1026 U 2 0 AIG70219.1 putative lipoprotein YgeR precursor CDS 756 OM 9.93 1 AIG70290.1 Uridine kinase family protein CDS 714 U 2 0 AIG70298.1 Putative metalloprotease yggG 759 U 2 U AIG70300.1 hypothetical protein CDS 732 U 2.5 0 AIG70312.1. UPF0301 protein YqgE CDS 564 U 2 0 AIG70323.1 Uncharacterized protein YggN CDS 720 U 2.5 0 AIG70398.1 Modulator of drug activity B CDS 582 U 2 0 AIG70405.1 Ferrichrome-iron receptor CDS 2142 OM 10 0 AIG70411.1 Type I secretion outer membrane protein, 1482 OM 10 0 TolC precursor CDS AIG70414.1 Uncharacterized protein ygiD CDS 816 U 2 0 AIG70516.1 type 1 fimbriae anchoring protein FimD 2592 OM 10 0 CDS AIG70532.1 Putative lipid carrier protein CDS 525 U 2 0 AIG70535.1 Putative protease 879 U 2 U AIG70568.1 putative ABC transporter, auxiliary 636 U 2.5 0 component YrbC CDS AIG70569.1 putative ABC transporter, periplasmic 552 U 2.5 1 component YrbD CDS AIG70575.1 Uncharacterized protein YrbK clustered 576 U 2 1 with lipopolysaccharide transporters CDS AIG70604.1 Outer membrane stress sensor protease 1368 P U DegQ, serine protease AIG70605.1 Outer membrane stress sensor protease 1068 P U DegS AIG70619.1 Rod shape-determining protein MreC CDS 1104 U 2 1 AIG70742.1 Type IV pilus biogenesis protein PilM CDS 795 U 2 0 AIG70779.1 hypothetical protein CDS 993 U 2.5 0 AIG70798.1 hypothetical protein CDS 912 U 2 0 AIG70844.1 Putative transmembrane protein CDS 606 U 2.5 0 AIG70880.1 hypothetical protein CDS 753 U 2 0 AIG70893.1 TonB-dependent hemin, ferrichrome 1983 OM 10 0 receptor CDS AIG70922.1 Uncharacterized protein YhjG CDS 2061 U 2 2 AIG70925.1 Protein YhjJ, putative peptidase CDS 1497 U 2.5 0 AIG70935.1 hypothetical protein CDS 1560 U 2 0 AIG70950.1 Putative fimbrial protein CDS 1056 Ex 9.65 1 AIG70952.1 Long polar fimbria protein A precursor 525 Ex 9.72 0 CDS AIG70954.1 Putative lipase CDS 699 U 7 1 AIG70958.1 Outer membrane protein A precursor CDS 660 OM 10 3 AIG70960.1 putative exported protein CDS 711 U 2.5 0 AIG70976.1 BAX protein CDS 573 U 2 0 AIG70983.1 Putative outer membrane protein yiaT 741 OM 10 1 precursor CDS AIG70995.1 core protein CDS 4230 U 2 0 AIG71007.1 hypothetical protein CDS 4767 OM 9.95 2 AIG71034.1 Lipopolysaccharide heptosyltransferase III 1023 U 2 0 CDS AIG71060.1 Putative exported protein CDS 1710 U 2 1 AIG71083.1 Secreted protein EspB CDS 939 Ex 10 1 AIG71084.1 Secreted protein EspD CDS 1125 Ex 10 3 AIG71087.1 Type III secretion system EscD protein 1221 U 2 1 CDS AIG71088.1 Intimin CDS 2805 OM 10 2 AIG71090.1 translocated intimin receptor Tir CDS 1677 Ex 10 2 AIG71096.1 SepQ CDS 918 U 2 0 AIG71102.1 Type III secretion bridge between inner and 573 OM 9.93 0 outermembrane lipoprotein (YscJ, HrcJ, EscJ, PscJ) CDS AIG71104.1 Type III secretion outermembrane pore 1539 OM 10 0 forming protein (YscC, MxiD, HrcC, InvG) CDS AIG71117.1 ROrf2 CDS 1146 Ex 10 0 AIG71137.1 hypothetical protein CDS 624 U 2 0 AIG71158.1 Uncharacterized protein YidR CDS 1251 U 2 0 AIG71159.1 Uncharacterized protein YidS CDS 1083 U 2 0 AIG71177.1 hypothetical protein CDS 750 U 2 0 AIG71181.1 hypothetical protein CDS 2409 U 5.48 0 AIG71182.1 hypothetical protein CDS 672 U 2 0 AIG71192.1 Putative fimbrial protein CDS 1083 Ex 10 0 AIG71193.1 Putative fimbrial protein CDS 1071 Ex 9.65 0 AIG71194.1 type 1 fimbriae anchoring protein FimD 2535 OM 9.93 1 CDS AIG71272.1 hypothetical protein CDS 903 U 2.5 0 AIG71273.1 hypothetical protein CDS 765 U 2.5 0 AIG71277.1 hypothetical protein CDS 849 OM 9.49 0 AIG71291.1 Putative carboxymethylenebutenolidase 816 U 2 0 CDS AIG71333.1 Outer membrane sugar transport protein 693 OM 9.93 1 YshA CDS AIG71349.1 hypothetical protein CDS 915 U 2 1 AIG71360.1 hypothetical protein CDS 1056 U 4.9 0 AIG71365.1 Putative glycoporin CDS 1395 U 2.5 0 AIG71378.1 hypothetical protein CDS 675 U 2 0 AIG71388.1 Putative uncharacterized protein YiiQ CDS 600 U 2.5 1 AIG71408.1 core protein CDS 4185 U 2 0 AIG71411.1 hypothetical protein CDS 609 U 2.5 0 AIG71419.1 hypothetical protein CDS 618 U 2.5 0 AIG71443.1 Outer membrane vitamin B12 receptor BtuB 1845 OM 10 0 CDS AIG71471.1 hypothetical protein CDS 636 U 2 0 AIG71532.1 NMN phosphatase CDS 714 U 2.5 1 AIG71558.1 Putative exported protein CDS 690 U 2.5 0 AIG71638.1 Outer membrane lipoprotein BLc CDS 534 OM 10 1 AIG71658.1 MflK protein CDS 1260 U 5.48 1 AIG71669.1 hypothetical protein CDS 639 U 2 0 AIG71674.1 YjfP protein CDS 750 U 2 0 AIG71687.1 Uncharacterized protein yjfZ CDS 795 U 2 0 AIG71690.1 putative virulence protein CDS 1149 U 2 0 AIG71691.1 Putative cell envelope opacity-associated 639 U 2 0 protein A CDS AIG71701.1 Protein ytfJ precursor CDS 555 U 4.9 0 AIG71707.1 Uncharacterized protein YtfM precursor 1734 OM 10 0 CDS AIG71708.1 Uncharacterized protein YtfN CDS 3780 U 4.72 1 AIG71752.1 hypothetical protein CDS 1503 U 2 0 AIG71763.1 hypothetical protein CDS 774 U 2.5 0 AIG71781.1 hypothetical protein CDS 981 U 2 0 AIG71788.1 type 1 fimbriae major subunit FimA CDS 549 Ex 10 1 AIG71791.1 type 1 fimbriae anchoring protein FimD 2637 OM 10 0 CDS AIG71794.1 mannose-specific adhesin FimH CDS 903 U 4.65 2 AIG71800.1 Uncharacterized protein YjiC CDS 831 U 2 0 AIG71813.1 hypothetical protein CDS 843 U 4.9 1 AIG71857.1 hypothetical protein CDS 1074 U 2 0 AIG68360.1 internalin, putative_EDL933_2172 1260 U 2 0 .sup.1PSORT Localization, where Ex = Extracellular, OM = Outer Membrane, P = Periplasmic, U = Unknown .sup.2Number of internal helices, where U = unknown

    TABLE-US-00004 TABLE S2 Vaccine candidates expressed at transcriptional level (cutoff >10 RPKM) Expression (absolute value RPKM) Protein Locus Functional PSORT RPKM RPKM RPKM (LB RPKM (LB ID Tag annotation score (LB) (LB agar) antibiotics) Feces) AIG66267.1 EDL933_0059 hypothetical protein CDS 2 32.7 65.6 75.0 0.0 AIG66347.1 EDL933_0139 Fimbrial protein Yad like 2 192.8 327.0 101.7 347.5 protein CDS AIG66348.1 EDL933_0140 Fimbrial protein YadK CDS 2 32.2 37.6 0.0 171.7 AIG66349.1 EDL933_0141 Fimbrial protein YadL CDS 2.5 44.4 48.9 0.0 134.0 AIG66424.1 EDL933_0216 putative aminopeptidase CDS 2.5 9.8 18.5 105.7 0.0 AIG66447.1 EDL933_0241 hypothetical protein CDS 2 223.3 250.2 288.3 779.5 AIG66490.1 EDL933_0284 putative tail fiber protein CDS 2 12 0.0 1305.2 51.1 AIG66511.1 EDL933_0305 Zinc binding domain protein CDS 2 11 10.6 48.4 30.4 AIG66518.1 EDL933_0312 hypothetical protein CDS 2.5 24.6 0.0 24.8 0.0 AIG66656.1 EDL933_0452 Protein YkiA CDS 2 8.3 6.8 0.0 28.1 AIG66781.1 EDL933_0577 Putative stomatin/prohibitin- 2 45.2 225.9 0.0 619.2 family membrane protease subunit YbbK AIG66972.1 EDL933_0770 core protein CDS 2 6.8 12.9 6.7 4.8 AIG66984.1 EDL933_0782 hypothetical protein CDS 2.5 21.6 18.6 13.3 38.2 AIG66987.1 EDL933_0786 putative fimbrial-like 9.72 41.5 17.4 24.9 143.2 protein ygiL precursor CDS AIG67020.1 EDL933_0819 TolA protein CDS 2 454.8 283.4 405.1 325.5 AIG67060.1 EDL933_0859 Putative outer membrane 2.5 45.5 30.9 338.2 126.9 protein CDS AIG67245.1 EDL933_1046 Urease accessory protein 2 23.2 0.0 0.0 0.0 UreF CDS AIG67308.1 EDL933_1109 putative hemolysin activator 8.86 0 0.0 13.3 19.1 protein CDS AIG67453.1 EDL933_1258 hypothetical protein CDS 2 68 51.0 383.0 131.1 AIG67464.1 EDL933_1259 Hypothetical protein CDS 2 24.9 27.4 78.4 0.0 AIG67503.1 EDL933_1308 hypothetical protein CDS 9.71 35.7 45.9 0.0 53.9 AIG67577.1 EDL933_1383 Shiga-like toxin II subunit 2.5 372.9 262.4 566.2 42.3 A precursor CDS AIG67652.1 EDL933_1458 Putative exported protein 2 17.5 9.1 13.0 37.4 precursor CDS AIG67653.1 EDL933_1459 outer membrane fimbrial 10 11.5 7.8 0.0 72.4 usher protein CDS AIG67671.1 EDL933_1477 hypothetical protein CDS 2 2.8 0.0 0.0 25.7 AIG67672.1 EDL933_1478 hypothetical protein CDS 2 2.4 0.0 0.0 21.9 AIG67760.1 EDL933_1570 putative hemolysin 8.86 3.2 4.6 13.3 76.2 activator protein CDS AIG67905.1 EDL933_1717 hypothetical protein CDS 2 32.4 8.4 144.1 138.1 AIG67914.1 EDL933_1726 Hypothetical protein CDS 2 3.5 0.0 0.0 10.5 AIG67963.1 EDL933_1775 hypothetical protein CDS 2 484.9 491.2 1537.0 2182.8 AIG68016.1 EDL933_1828 hypothetical protein CDS 2 3.8 0.0 8.8 12.7 AIG68165.1 EDL933_1977 Putative intestinal colonization 2 30 171.9 0.0 135.9 factor encoded by prophage CP-933O CDS AIG68173.1 EDL933_1985 Hypothetical protein CDS 2 70.7 40.0 7.6 10.9 AIG68238.1 EDL933_2050 Hypothetical protein CDS 2 53.3 26.7 45.8 0.0 AIG68357.1 EDL933_2169 Outer membrane porin 10 16.3 22.4 0.0 110.6 protein NmpC precursor CDS AIG68359.1 EDL933_2171 hypothetical protein CDS 2 1.7 14.8 0.0 30.3 AIG68376.1 EDL933_2189 internalin, putative CDS 2 6.3 2.3 10.1 19.3 AIG68484.1 EDL933_2297 Hypothetical protein CDS 2 8.5 8.0 30.5 10.9 AIG68679.1 EDL933_2505 Hypothetical protein CDS 2 27.2 13.3 15.3 21.9 AIG68688.1 EDL933_2514 hypothetical protein CDS 2 76.6 33.8 0.0 242.9 AIG69057.1 EDL933_2888 putative membrane protein CDS 2 606.7 933.1 401.2 1262.9 AIG69153.1 EDL933_2986 hypothetical protein CDS 2 108.7 83.4 119.1 142.8 AIG69189.1 EDL933_3022 Hypothetical protein CDS 2 18.8 10.7 30.5 0.0 AIG69198.1 EDL933_3031 hypothetical protein CDS 2 37.7 78.8 25.0 180.0 AIG69346.1 EDL933_3180 Uncharacterized protein 2 14.1 0.0 0.0 19.6 YehA precursor CDS AIG69349.1 EDL933_3183 Putative fimbrial-like 2.5 88.7 582.1 208.0 37.4 protein CDS AIG69390.1 EDL933_3224 Minor tail protein Z CDS 2 3.6 0.0 22.6 0.0 AIG69393.1 EDL933_3227 Prophage Clp protease- 2.2 0.0 13.6 0.0 like protein AIG69411.1 EDL933_3245 Shiga toxin A-chain 2.5 654.7 1586.3 871.2 235.5 precursor CDS AIG69664.1 EDL933_3500 Uncharacterized protein 2 33.2 93.7 50.2 72.2 YadU in stf fimbrial cluster CDS AIG69958.1 EDL933_3799 Hypothetical protein CDS 2 31.4 16.0 22.8 21.9 AIG70298.1 EDL933_4145 Putative metalloprotease yggG 2 519.6 390.4 93.0 320.9 AIG70798.1 EDL933_4653 hypothetical protein CDS 2 3.7 0.0 15.5 22.3 AIG70844.1 EDL933_4699 Putative transmembrane 2.5 10.2 0.0 0.0 0.0 protein CDS AIG71087.1 EDL933_4946 Type III secretion system 2 55.1 44.5 46.2 83.1 EscD protein CDS AIG71096.1 EDL933_4955 SepQ CDS 2 223.3 102.2 399.8 309.6 AIG71137.1 EDL933_4996 hypothetical protein CDS 2 19.8 39.6 22.6 130.1 AIG71181.1 EDL933_5041 hypothetical protein CDS 5.48 5.6 0.0 111.3 16.9 AIG71182.1 EDL933_5042 hypothetical protein CDS 2 0 14.7 84.0 151.0 AIG71349.1 EDL933_5210 hypothetical protein CDS 2 6.1 16.2 0.0 0.0 AIG71763.1 EDL933_5624 hypothetical protein CDS 2.5 34.7 82.9 145.9 26.2 AIG71811.1 EDL933_5672 adherence and invasion 9.95 17.3 23.5 11.2 64.5 outermembrane protein (Inv, enhances Peyer's patches colonization) CDS AIG66227.1 EDL933_0019 Putative outer membrane 10.00 3.2 10.1 0.0 8.3 protein EDL933 0019 AIG68053.1 EDL933_1865 Pertactin precursor 7.00 36.6 42.0 40.0 28.8 AIG68360.1 EDL933_2172 internalin, putative 2.00 8 7.8 11.2 145.0 AIG69216.1 EDL933_3049 adherence and invasion 9.95 5.8 12.6 10.8 10.3 outermembrane protein (Inv, enhances Peyer's patches colonization) AIG69974.1 EDL933_3815 Pertactin precursor 5.87 12 21.8 3.3 47.1 AIG68899.1 EDL933_2727 Putative lipoprotein 2 11 6.9 0 0

    TABLE-US-00005 TABLE S3 Features of the 24 antigen candidates expressed as recombinant proteins Expression (absolute value RPKM) Protein Functional Pfam LB LB No. ID Desig annotation Sol. kDa Localization domain LB Agar Antibiotics Feces WB 1 AIG67060.1 MC001 Putative outer I 35 OM DUF2219 45.5 30.9 338.2 126.9 ++ membrane protein 2 AIG68165.1 MC002 Putative intestinal S 27 EC SBP bac 11 30 171.9 0 135.9 ++ colonization factor encoded by prophage CP-933O 3 AIG68357.1 MC003 Outer membrane porin I 41 OM Porin 1 16.13 22.4 0 110.6 + protein NmpC precursor 4 AIG67577.1 MC004 Shiga-like toxin I 36 EC RIP 372 262.4 566.2 42.3 + II subunit A precursor 5 AIG69411.1 MC005 Shiga toxin S 35 EC RIP 654.7 1586.3 871.2 235.5 − A-chain precursor 6 AIG66347.1 MC006 Fimbrial protein Yad S 40 OM Fimbrial 192.8 327 101.7 347.5 − like protein 7 AIG66424.1 MC007 putative aminopeptidase S 30 Unknown unknown 9.8 18.5 105.7 0 ++ 8 AIG66984.1 MC008 hypothetical protein I 40 Fimbrial Fimbrial 21.6 18.6 13.3 38.2 + 9 AIG67652.1 MC009 Putative exported I 38 OM Fimbrial 17.5 9.1 13 37.4 ++ protein precursor 10 AIG67671.1 MC010 hypothetical protein I 31 Unknown DUF1329 2.8 0 0 25.7 + 11 AIG67672.1 MC011 hypothetical protein I 51 OM unknown 2.4 0 0 21.9 + 12 AIG68053.1 MC012 Pertactin precursor I 25 OM unknown 36.6 42 40 28.8 + 13 AIG68360.1 MC013 internalin, putative S 48 Unknown unknown 8 7.8 11.2 145 + 14 AIG68899.1 MC014 putative lipoprotein S 25 OM SIMPL 11 6.9 0 0 − 15 AIG69664.1 MC015 Uncharacterized protein I 31 Unknown DUF2544 33.2 93.7 50.2 72.2 − YadU in stf fimbrial cluster 16 AIG70798.1 MC016 hypothetical protein I 34 Unknown DUF4225 3.7 0 15.5 22.3 − 17 AIG67308.1 MC017 putative hemolysin I 37 OM Potra 2 0 0 13.3 19.1 + activator protein 100% ID 18 AIG66972.1 MC018 core protein S 159 Unknown unknown 6.8 12.9 6.7 4.8 + 19 AIG69216.1 MC019 adherence and invasion S 275 OM Invasin 5.8 12.6 10.8 10.3 − outermembrane protein (Inv, enhances Peyer's patches colonization) 20 AIG69974.1 MC020 Pertactin precursor S 148 OM AIDA/Pertectin 12 21.8 3.3 47.1 ++ 21 AIG71811.1 MC021 adherence and invasion S 181 OM DUF3442 17.3 23.5 11.2 64.5 − outer membrane protein (Inv, enhances Peyer's patches colonization) 22 AIG71181.1 MC022 hypothetical protein S 93 Unknown unknown 5.6 0 111.3 16.9 + 23 AIG66227.1 MC023 Putative outer S 92 OM PapC Usher 3.2 10.1 0 8.3 + membrane protein 24 AIG66656.1 MC024 Protein YkiA I 83 Unknown DUF2773 8.3 6.8 0 28.1 + S = soluble; I = insoluble OM = Outer membrane; EC = extracellular

    TABLE-US-00006 able S4. Primers Notes (ID, Primer Sequence Product purpose) MCRL-34Fw CTGTACTTCCAGGGCTTTCAACCAATACTTAATGAT MC001 AIG67060.01 [SEQ ID NO: 49] MCRL-34Rv AATTAAGTCGCGTTAAAAAAAGAAGGTGATTGC [SEQ ID NO: 50] MCRL-24Fw CTGTACTTCCAGGGCGATATCAATCTGTATGGTCC MC002 AIG68165.1 [SEQ ID NO: 51] MCRL-24Rv AATTAAGTCGCGTTAAGTGCCTTTCCTGGT [SEQ ID NO: 52] MCRL-40Fw CTGTACTTCCAGGGCGACCTTTATGGCAAGG MC003 AIG68357.1 [SEQ ID NO: 53] MCRL-40Rv AATTAAGTCGCGTTAGAACTGATAGGTAATGCC [SEQ ID NO: 54] MCRL-35Fw CTGTACTTCCAGGGCGAGTTTACGATAGACTTTTCG MC004 AIG67577.1 [SEQ ID NO: 55] MCRL-35Rv AATTAAGTCGCGTTATTTACCCGTTGTATATAAAAAC [SEQ ID NO: 56] MCRL-32Fw CTGTACTTCCAGGGCACGTATGTAGATTCGCTG MC005 AIG69411.1 [SEQ ID NO: 57] MCRL-32Rv AATTAAGTCGCGTTAACTGCTAATAGTTCTGCG [SEQ ID NO: 58] MCRL-41Fw CTGTACTTCCAGGGCATGAAGATAAGCTCTACT MC006 IAG66347.1 [SEQ ID NO: 59] MCRL-41Rv AATTAAGTCGCGTTATTCGTAGGTAAAGGA [SEQ ID NO: 60] MCRL-28Fw CTGTACTTCCAGGGCCAGCAACTGACAGACAA MC007 AIG66424.1 [SEQ ID NO: 61] MCRL-28Rv AATTAAGTCGCGTTACTGGAATCGACTCACC [SEQ ID NO: 62] MCRL-36Fw CTGTACTTCCAGGGCAACTGCTATTTTGGTACC MC008 AIG66984.1 [SEQ ID NO: 63] MCRL-36Rv AATTAAGTCGCGTTAGTTGTAGTTAATTTTGAAAAG [SEQ ID NO: 64] MCRL-38Fw CTGTACTTCCAGGGCATGTGGGAATGTGATG MC009 AIG67652.1 [SEQ ID NO: 65] MCRL-38Rv AATTAAGTCGCGTTATTGCATTTTCACCAA [SEQ ID NO: 66] MCRL-26Fw CTGTACTTCCAGGGCACGCTGACGGTAACGG MC010 AIG67671.1 [SEQ ID NO: 67] MCRL-26Rv AATTAAGTCGCGTTATTTCGCACCTCGCTG [SEQ ID NO: 68] MCRL-43Fw CTGTACTTCCAGGGCACGCTTTACGAGCAG MC011 AIG67672.1 [SEQ ID NO: 69] MCRL-43Rv AATTAAGTCGCGTTATAGATAGTATTTAAAGCCGT [SEQ ID NO: 70] MCRL-22Fw CTGTACTTCCAGGGCGTGGGGATCGACAGC MC012 AIG68053.1 [SEQ ID NO: 71] MCRL-22Rv AATTAAGTCGCGTTAGAACGACCAGTTCACAC [SEQ ID NO: 72] MCRL-42Fw CTGTACTTCCAGGGCATGAAATTCCCTTCA MC013 AIG68360.1 [SEQ ID NO: 73] MCRL-42Rv AATTAAGTCGCGTTAGTGATAAAAAGGCCA [SEQ ID NO: 74] MCRL-23Fw CTGTACTTCCAGGGCGGTTATTTTGTTGGCG MC014 AIG68899.1 [SEQ ID NO: 75] MCRL-23Rv AATTAAGTCGCGTTAATCCTGCAACGCATA [SEQ ID NO: 76] MCRL-29Fw CTGTACTTCCAGGGCATTTATTATGCGATGAAA MC015 AIG69664.1 [SEQ ID NO: 77] MCRL-29Rv AATTAAGTCGCGTTACAGTTCATTCAGTACATACTG [SEQ ID NO: 78] MCRL-30Fw CTGTACTTCCAGGGCATGGGTACAGCAGCTATA MC016 AIG70798.1 [SEQ ID NO: 79] MCRL-30Rv AATTAAGTCGCGTTATTGTATTCCTGCACCA [SEQ ID NO: 80] MCRL-37Fw CTGTACTTCCAGGGCGATGTCCGGCGTAGC MC017 AIG67308.1 [SEQ ID NO: 81] MCRL-37Rv AATTAAGTCGCGTTACTGCTTTTTACAACCATTC [SEQ ID NO: 82] MCRL-48Fw CTGTACTTCCAGGGCATGAGCGGAAAACCG MC018 AIG66972.1 [SEQ ID NO: 83] MCRL-48Rv AATTAAGTCGCGTTATTTTCTTATTCCTCTCGATG [SEQ ID NO: 84] MCRL-52Fw CTGTACTTCCAGGGCATGGCTGCGGCAGCA MC019 AIG69216.1 [SEQ ID NO: 85] MCRL-52Rv AATTAAGTCGCGTTACGCAATATTGACGAT [SEQ ID NO: 86] MCRL-49Fw CTGTACTTCCAGGGCGTGGGGCAGTCTAAT MC020 AIG69974.1 [SEQ ID NO: 87] MCRL-49Rv AATTAAGTCGCGTTAACTCGCTTTCATTATGTT [SEQ ID NO: 88] MCRL-51Fw CTGTACTTCCAGGGCGTGCCTTACACGCTTGGT MC021 AIG71811.1 [SEQ ID NO: 89] MCRL-51Rv AATTAAGTCGCGTTAAAGTGATTTACGGCAGGC [SEQ ID NO: 90] MCRL-45Fw CTGTACTTCCAGGGCATGGTCGCTAAATTAAAAC MC022 AIG71181.1 [SEQ ID NO: 91] MCRL-45Rv AATTAAGTCGCGTTAAGCCTGGGTTATATTAAC [SEQ ID NO: 92] MCRL-45Fw CTGTACTTCCAGGGCATGGTCGCTAAATTAAAAC MC023 AIG66227.1 [SEQ ID NO: 93] MCRL-45Rv AATTAAGTCGCGTTAAGCCTGGGTTATATTAAC [SEQ ID NO: 94] MCRL-46Fw CTGTACTTCCAGGGCAGTTATGGCCGATTT MC024 AIG66656.1 [SEQ ID NO: 95] MCRL-46Rv AATTAAGTCGCGTTATGTAAACTGCACATAAGA [SEQ ID NO: 96] pET-TEV-Fw TAACGCGACTTAATTCTAGCATAACC pET15 pET-15 [SEQ ID NO: 97] expression pET-REV-Rv GCCCTGGAAGTACAGGTTTTC vector [SEQ ID NO: 98] TolR-Cat-Fw TGGAGGTCGATTTGCCAGACGCTACTGAATCACAGGCGGTGAGCAGTAACGATA Cat-TolR tolR mutant ATCCGCCAGTGATTGTTGACATATGAATATCCTCCTTAGTTCCTATTCC construction [SEQ ID NO: 99] TolR-Cat-Rv CCTTGAAACGGCTGGACACTTCCGCCACCACCTGCTCTGGTGGTAAACGCTCCA GGCGATCTTTCTCAACCAGTGTAGGCTGGAGCTGCTTCGAAG [SEQ ID NO: 100] GMMA- CAGGAGGAATTAACCATGAAAAAAAGTGTCATCGCTGGC MC001 with Antigen MC001Fw [SEQ ID NO: 101] signal expression on GMMA- ATGATGATGATGATGATGAAAAAAGAAGGTGATTGCTCC sequence GMMA MC001Rv- [SEQ ID NO: 102] NONhis GMMA- CAGGAGGAATTAACCATGGGGGCAGTCTAATAATACCAC MC007 with Antigen MC007Fw [SEQ ID NO: 103] signal expression on GMMA- ATGATGATGATGATGATGGAACGACCAGTTCACACCAGC sequence GMMA MC007Rv- [SEQ ID NO: 104] NONhis GMMA- CAGGAGGAATTAACCATGGGGGCAGTCTAATAATACCACC MC020 with Antigen MC020Fw [SEQ ID NO: 105] signal expression on GMMA- ATGATGATGATGATGATGGAACGACCAGTTCACACCAG sequence GMMA MC020Rv- [SEQ ID NO: 106] NONhis MC001tagFw GATTACAAAGACGATGATGACAAGGATTACAAAGACGATGATGACAAGAACAGC MC001 with Antigen CTTGCATTATCATT signal expression on [SEQ ID NO: 107] sequence GMMA with MC001tagRv CTTGTCATCATCGTCTTTGTAATCCTTGTCATCATCGTCTTTGTAATCCGCGAT and Flag Flag Tag AGCTGAACACGTGG Tag [SEQ ID NO: 108] MC007tagFw GATTACAAAGACGATGATGACAAGGATTACAAAGACGATGATGACAAGTCTGAA MC007 with Antigen TCTTCTATTGATGA signal expression on (SEQ ID NO: 109] sequence GMMA with MC007tagRv CTTGTCATCATCGTCTTTGTAATCCTTGTCATCATCGTCTTTGTAATCGGCACA and Flag Flag Tag TCCTGCAAGCAGCG Tag [SEQ ID NO: 110] MC020tagFw GATTACAAAGACGATGATGACAAGGATTACAAAGACGATGATGACAAGGCCTTC MC020 with Antigen ACTCCTGATGTTAT signal expression on [SEQ ID NO: 111] sequence GMMA with MC020tagRv CTTGTCATCATCGTCTTTGTAATCCTTGTCATCATCGTCTTTGTAATCAGCCATC and Flag Flag Tag CCGGGCGGGGCAT Tag [SEQ ID NO: 112] pBADRv CATGGTTAATTCCTCCTGTTAGCCC pBAD Expression [SEQ ID NO: 113] Vector of Ag in pBADFw TGAGTTTAAACGGTCTCCAGCTTGG without GMMA NonHIS [SEQ ID NO: 114] His-Tag

    TABLE-US-00007 TABLE 5 Nucleotide and Protein Sequences of the 24 Antigen Candidates Sequence Name Sequence Length MC001 ATGAAAAAAAGTGTCATCGCTGGCGTCTTTATTGCTCTGTCATTTACCACGTGTTCAGCTATCGCGAAG  960 AGCCTTGCATTATCATTAGCAAATGATGATGCAGGGAAGTTTCAACCAATACTTAATGATATTTATGGC AATAAACATGAAAACAGAGATGATTACTCACAAGGCTTATTTCTGGGATATAGCCACGATATCTCAGAC TCGAGCCAATTATCTCTCCATATTGCGCAAGATATTTACTCTCCATCAGGCAGTAATAAAAGACACAAC ACAGCTGTAACTGGAGACAGAGCTTTTAGTGCATACACTCACACTGGTATTGAATGGAACTCCCTTGCG AATGACTGGATTCGCTATCGATTAGGTACTGACATAGGTGTTGTTGGCCCCGACGCAGGCGGTCAGAAA GTACAAAATAAAGCTCATGAGATTATTGGGGCAGAAAAATATCATGCATGGGATGATCAAATAGAGAAT CGCTACGGTTATACTGTAAAAGGGATGCTATCCATGACACCAAGTATGGATATTTTAGGTGCTAATGTT GGATTATACCCTGAAGTTTCTGCTGTTACTGGAAACTTATTTCAATATGTAGCATATGGCGCAACCATT GCCATTGGTAATGATAAAACCTTCAATTCGGATAATGGCTTTGGTCTGCTGGCTCCCCGTGGTTTAATG CATATGTCCGATACAAGCGGATTCAAATACAAGATTTTTGCAGGTATGGAAAGACGAGATGTCAATCGC AACTATACTCTCGAAGGAAAAACAATACAGACGAAACAAACAACAGTATCGCTAAACAAAACTGTTGAT GAATATCAAGTTGGCGCAACAATTGGGTATGCACCTGTAGCCTTCACACTAGCATTTAATAAAGTAACA TCAGAATTCAAGACAGGGGATGACTATTCATTTATAAATGGAGCAATCACCTTCTTTTTTTAA [SEQ ID NO: 1] MC001 MKKSVIAGVFIALSFTTCSAIANSLALSLANDDAGKFQPILNDIYGNKHENRDDYSQGLFLGYSHDISD  319 prot SSQLSLHIAQDIYSPSGSNKRHNTAVTGDRAFSAYTHTGIEWNSLANDWIRYRLGTDIGVVGPDAGGQK VQNKAHEIIGAEKYHAWDDQIENRYGYTVKGMLSMTPSMDILGANVGLYPEVSAVTGNLFQYVAYGATI AIGNDKTFNSDNGFGLLAPRGLMHMSDTSGFKYKIFAGMERRDVNRNYTLEGKTIQTKQTTVSLNKTVD EYQVGATIGYAPVAFTLAFSKVTSEFKTGDDYSFINGAITFFF [SEQ ID NO: 25] MC007 ATGAATTCAAAAAAGCTTTGTTGCATATGTGTGTTATTCTCGCTGCTTGCAGGATGTGCCTCTGAATCT  801 TCTATTGATGAAAAGAAGAAAAAAGCTCAAGTCACACAAAGTAATATTAATAAAAACACTCCCCAGCAA CTGACAGACAAAGATTTATTCGGTAATGAAACCACTCTGGCCGTATCCGAAGAGGATATTCAAGCAGCG CTTGATGGAGATGAGTTCCGCGTTCCCCTTAATTCTCCTGTAATACTTGTTCAATCCGGCAACCGCGCA CCGGAAACCATTATGCAGGAGGAGATGCGAAAATATTATACTGTTTCCACATTCTCTGGTATCCCGGAC AGGCAAAAGCCTCTGACTTGTAACAAAAACAAAGATAAAAATGAGAACGAGGATGTTGCCCGTGCTGAG AATATGAACTGGATGGAGGCACTGCGTTTTGTGGCTGCAAAAGGACATCAGAAAGCGATTATTGTTTAC CAGGATATGTTGCAGACAGGAAAATATGACTCTGCGCTGAAATCAACAGTATGGTCCGACTATAAAAAT GAAAAACTCACTGACGCTATCTCCCTGCGCTACCTGGTACGTTTCACGCTGGTGGATGTGGCAACAGGT GAGTGGGCTACCTGGTCGCCGGTGAATTATGAATCGAGAGTAATTTTTCCGCCGGCTGGAATAACAAAA ACGAGCAATAAAGAACTATCAAATGACCATGTTACGGAAGCGCAACTGTTTAATTTGAAACAAAAAACA TATGTATCGATGGTGAAAGACTTGGTGAGTCGATTCCAGTAA [SEQ ID NO: 2] MC007 MNSKKLCCICVLFSLLAGCASESSIDEKKKKAQVTQSNINKNTPQQLTDKDLFGNETTLAVSEEDIQAA  266 pro& LDGDEFRVPLNSPVILVQSGNRAPSTIMQEEMRKYYTVSTFSGIPDRQKPLTCNKNKDKNENEDVARAE NMNWMQALRFVAAKGHQKAIIVYQDMLQTGKYDSALKSTVWSDYKNEKLTDAISLRYLVRFTLVDVATG EWATWSPVNYESRVIFFPAGITKTSNKELSNDHVTEAQLFNLKQKTYVSMVKDLVSRFQ [SEQ ID NO: 26] MC020 ATGAACAGGACCAGTCCCTATTATTGTCGTGGCTCAGTACTTTCCTTATTGATATCTGCCTTGATATAT 4587 GCCCCGCCCGGGATGGCTGCCTTCACTCCTGATGTTATTGGTGTGGTAAACGATGAGACTGTAGATGGC AGCCAACGAGTAGATGAACGAGGTACAACAAATAACACTCATATTATCAACCATGGCCAGCAGAATGTT TATGGCGGGGTATCTAATGGAAGTCTTATTGAATCTGGTGGATATCAAGATGTAGGAAGGCATAACAAT TATGTGGGGCAGTCTAATAATACCACCATTAACGGGGGCAGACAGTCAATTCATGACGGGGGTATTTCC ACAGGTACGATAATCGAGAGTGGCAATCAGGACGTTTATAAAGGGGGTATCAGCAATGGAACGACAATT AAGGGCGGTGCTTCACGCGTAGAGGGAGGGAGTGCGAATGGAACACTCATTGATGGTGGTAGCCAGATA GTAAAAGTTCAAGGGCATGCTGATGGTACAACGATAAATAAGTCTGGCTCTCAGGACGTAGTACAAGGA AGTCTGGCAACGAACACAACCATAAATGGTGGTCGACAGTATGTTGAACAGAGCACAGTAGAAACAACC ACCATCAAAAATGGCGGTGAGCAAAGAGTATATGAGAGCCGTGCGCTGGACACGACGATTGAAGGCGGA ACTCAGTCTCTGAATAGTAAGTCAACGGCAAAAAATACTCAGATCTATTCTGGTGGTACGCAAATTATT GATAACACCAGCTCCTCGGATGTTATTGAAGTTTATTCCGGTGGCGTGCTTGATGTTAGTGGTGGTACG GCAACAAATGTTACCCAGCACGATGGTGCAATTTTAAAAACTAACACTAACGGTACGACGGTGAGCGGT ACGAATAGTGAAGGTGCATTCTCCATCCACAATCACGTGGCAGACAATGTGTTGCTGGAAAACGGTGGT CATTTAGACATAAACGCATATGGTTCGGCAAACAAGACGATTATTAAAGATAAAGGAACAATGTCAGTT TTAACCAATGCTAAAGCTGATGCGACCCGAATAGATAATGGCGGGGTTATGGATGTTGGAGGAAACGCG ACAAATACCATAATTAATGGTGGCACACAGAATATTAATAATTATGGCATAGCCACAGGCACCAATATC AACAGCGGAACGCAAAATATCAAAAGCGGCGGGAAAGCTGACACAACAATTATATCCTCCGGGAGCCGG CAGGTTGTTGAGAAAGATGGTACGGCAATTGGCAGCAATATTAGCGCCGGAGGCTCGCTGATTGTCTAT ACCGGCGGTATTGCACATGGGGTTAACCAGGAGACGGGCAGTGCTTTAGTTGCCAACACGGGTGCAGGG ACTGATATCGAAGGATACAACAAGCTCTCTCACTTCACTATTACCGGAGGGGAGGCTAATTATGTTGTG CTGGAAAATACCGGCGAACTGACGGTAGTGGCTAAAACCTCGGCGAAAAATACTACCATTGATGCTGGC GGTAAGCTGATTGTCCAGAAGGAGGCTAAAACAGATAGCACCAGACTTAATAATGGCGGCGTTCTGGAG GTTCAGGACGGTGGTGAGGCTAAGCATGTTGAGCAACAATCCGGCGGCGCATTAATTGCTTCCACGACC TCCGGAACACTTATCGAAGGAACCAACAGTTATGGTGATGCTTTCTACATCAGGAATTCAGAAGCTAAA AATGTAGTGCTGGAAAACGCTGGCTCATTAACAGTCGTCACTGGTTCCCGGGCAGTTGACACGATTATT AATGCCAACGGCAAAATGGATGTTTATGGAAAAGATGTTGGCACTGTACTCAATAGTGCTGGCACCCAA ACAATATATGCCAGTGCCACTTCTGATAAAGCAAATATCAAAGGTGGCAAGCAAACGGTATATGGTTTA GCCACTGAAGCAAATATCGAAAGTGGTGAACAAATTGTTGATGGTGGGTCAACAGAGAAAACACACATC AATGGTGGCACGCAAACCGTTCAGAATTATGGTAAGGCGATCAATACCGATATCGTCTCTGGCCTACAA CAAATTATGGCAAACGGGACAGCGGAAGGTTCCATTATTAATGGCGGTTCACAGATAGTTAATGAGGGC GGTCTGGCTGAAAACTCGGTGCTTAATGATGGCGGCACACTCGATGTGCGGGAGAAAGGCAGCGCAACG GGGATACAGCAGAGTAGCCAGGGCGCGTTGGTTGCAACCACCAGGGCGACGCGGGTCACAGGAACACGC GCGGATGGCGTCGCGTTCAGCATCGAGCAGGGTGCGGCGAACAATATCCTGCTGGCAAATGGCGGAGTG TTAACCGTGGAGTCAGACACCTCTTCTGACAAAACACAGGTCAATACGGGCGGACGGGAGATCGTCAAA ACAAAAGCCACTGCGACAGGCACGACGCTCACCGGCGGTGAACAAATTGTCGAGGGTGTGGCGAATGAG ACAACAATTAACGACGGCGGAATACAAACAGTTTCAGCTAACGGAGAGGCAATAAAAAGAACGATCAAT GAAGGCGGTACGCTGACAGTCAACGATAATGGGAAAGCGACAGATATCGTCCAGAACAGCGGTGCCGCT CTCCAGACGAGCACGGCTAACGGTATTGAAATCAGCGGTACTCACCAGTACGGCACTTTTTCCATTTCC GGCAATTTAGCGACCAATATGTTGCTGGAAAATGGCGGTAATTTATTGGTATTAGCAGGTACCGAAGCT CGCGACTCCACGGTTGGCAAGGGGGGGGCAATGCAAAACCAGGGTCAGGACTCCGCCACAAAGGTTAAC TCTGGTGGGCAATATACCCTTGGGCGGTCAAAAGATGAGTTTCAGGCTCTGGCCCGGGCAGAAGATCTC CAGGTTGCTGGCGGGACAGCAATCGTCTACGCAGGTACGCTGGCGGATGCATCGGTCAGTGGCGCGACA GGAAGCCTGTCGTTAATGACGCCACGGGATAATGTTACGCCAGTTAAACTCGAAGGGGCGATCCGGATT ACCGATAGCGCGACATTAACTATCGGCAATGGCGTTGATACGACGCTTGCCGACCTGACGGCTGCCAGC CGGGGCAGTGTCTGGCTTAACAGCAATAATTCCTGTGCAGGCACCAGCAACTGCGAGTATAGAGTAAAC AGTTTGCTACTTAACGACGGTAATGTTTATTTATCAGCACAAACAGCAGCGCCTGCCACAACTAACGGT ATATACAATACGCTGACAACCAATGAACTTTCCGGTAGCGGTAATTTCTACCTGCATACCAACGTTGCA GGCTCTCGGGGCGATCAACTGGTCGTCAACAACAACGCGACTGGTAATTTTAAAATCTTTGTTCAGGAT ACCGGCGTCAGTCCTCAGTCTGACGACGCGATGACGCTGGTGAAAACAGGGGGAGGGGATGCTTCGTTT TCGCTGGGCAATACTGGCGGTTTCGTTGATGTTGGGACCTATGAGTATGTCCTGAAAAGCGATGGCAAC AGCAACTGGAACCTGACCAATGATGTCAAACCCAACCCGGATCCCAACCCAAATCCCAACGCAAATCCG AAGCCGGATCCAAAACCAGACCCAAAACCGGATCCGAAACCAGACCCGACTCCCGAGCCAACGCCGACA CCCGTTCCGGAGAAACGCATCACGCCTTCTACCGCAGCCGTACTCAATATGGCAGCAACATTACCGTTG GTATTTGATGCTGAGCTAAACAGTATTCGCGAGCGGTTGAACATAATGAAAGCGAGTCCACACAACAAT AATGTCTGGGGGGCGACGTATAACACCCGTAATAATGTCACCACCGATGCGGGGGCCGGGTTTGAGCAG ACGCTGACCGGAATGACAGTGGGGATCGACAGCCCTAATGATATTCCTGAGGGGATTGCGACGCTGGGC GCTTTTATGGGTTATTCCCATTCACATATCGGTTTTGATCGCGGAGGACATGGCAGTGTGGGCAGTTAT TCTCTGGGCGGCTATGCCAGTTGGGAACATGAAAGTGGTTTCTATCTGGACGGTGTCGTGAAGCTGAAC CGTTTTGAAAGTAACGTAGCCGGTAAAATGAGCAGCGGTGGAGCCGCCAATGGCAGTTACCACAGCAAC GGGCTGGGCGGTCACATTGAAACCGGGATGCGATTTACCGATGGTAACTGGAACCTGACGCCGTATGCA TCGTTAACGGGGTTCACCGCTGATAACCCCGAATATCATTTATCCAATGGCATGGAATCGAAATCAGTC GATACCCGCAGTATATATCGTGAACTGGGCGCAACGCTGAGTTACAACATGCGTCTGGGGAACGGTATG GAAATTGAGCCGTGGCTGAAGGCGGCTGTGCGCAAAGAATTTGTCGATGATAACCGGGTGAAGGTGAAT AATGACGGTAATTTCGTCAATGATTTGTCGGGCAGACGTGGAATATACCAGGCAGGTATTAAAGCCTCA TTCAGCAGTACGTTAAGCGGGCATCTTGGGGTGGGGTATAGCCATGGTGCCGGTGTGGAATCGCCGTGG AACGCGGTAGCTGGTGTGAACTGGTCGTTCTGA [SEQ ID NO: 3] MC020 MNRTSPYYCRRSVLSLLISALIYAPPGMAAFTPDVIGVVNDETVDGSQRVDERGTTNNTHIINHGQQNV 1528 prot YGGVSNGSLIESGGYQDVGRHNNYVGQSNNTTINGGRQSIHDGGISTGTIIESGNQDVYKGGISNGTTI KGGASRVEGGSANGTLIDGGSQIVKVQGHADGTTINKSGSQDVVQGSLATNTTINGGRQYVEQSTVETT TIKNGGEQRVYESRALDTTIEGGTQSLNSKSTAKNTQIYSGGTQIIDNTSSSDVIEVYSGGVLDVSGGT ATNVTQHDGAILKTNTNGTTVSGTNSEGAFSIHNHVADNVLLENGGHLDINAYGSANKTIIKDKGTMSV LTNAKADATRIDNGGVMDVAGNATNTIINGGTQNINNYGIATGTNINSGTQNIKSGGKADTTIISSGSR QVVEKDGTAIGSNISAGGSLIVYTGGIAHGVNQETGSALVANTGAGTDIEGYNKLSHFTITGGEANYVV LENTGELTVVAKTSAKNTTIDAGGKLIVQKEAKTDSTRLNNGGVLEVQDGGEAKHVEQQSGGALIASTT SGTLIEGTNSYGDAFYIRNSEAKNVVLENAGSLTVVTGSRAVDTIINANGKMDVYGKDVGTVLNSAGTQ TIYASATSDKANIKGGKQTVYGLATEANIESGEQIVDGGSTEKTHINGGTQTVQNYGKAINTDIVSGLQ QIMANGTAEGSIINGGSQIVNEGGLAENSVLNDGGTLDVREKGSATGIQQSSQGALVATTRATRVTGTR ADGVAFSIEQGAANNILLANGGVLTVESDTSSDKTQVNTGGREIVKTKATATGTTLTGGEQIVEGVANE TTINDGGIQTVSANGEAIKTTINEGGTLTVNDNGKATDIVQNSGAALQTSTANGIEISGTHQYGTFSIS GNLATNMLLENGGNLLVLAGTEARDSTVGKGGAMQNQGQDSATKVNSGGQYTLGRSKDEFQALARAEDL QVAGGTAIVYAGTLADASVSGATGSLSLMTPRDNVTPVKLEGAIRITDSATLTIGNGVDTTLADLTAAS RGSVWLNSNNSCAGTSNCEYRVNSLLLNDGNVYLSAQTAAPATTNGIYNTLTTNELSGSGNFYLHTNVA GSRGDQLVVNNNATGNFKIFVQDTGVSPQSDDAMTLVKTGGGDASFSLGNTGGFVDLGTYEYVLKSDGN SNWNLTNDVKPNPDPNPNPNPNPKPDPKPDPKPDPKPDPTPEPTPTPVPEKRITPSTAAVLNMAATLPL VFDAELNSIRERLNIMKASPHNNNVWGATYNTRNNVTTDAGAGFEQTLTGMTVGIDSPNDIPEGIATLG AFMGYSHSHIGFDRGGHGSVGSYSLGGYASWEHESGFYLDGVVKLNRFESNVAGKMSSGGAANGSYHSN GLGGHIETGMRFTDGNWNLTPYASLTGFTADNPEYHLSNGMESKSVDTRSIYRELGATLSYNMRLGNGM EIEPWLKAAVRKEFVDDNRVKVNNDGNFVNDLSGRRGIYQAGIKASFSSTLSGHLGVGYSHGAGVESPW NAVAGVNWSF [SEQ ID NO: 27] MC002 ATGGCAGGTTTTTTAATATTCCTGTCTTCTGCTGCTTATGCTGATATCAATCTGTATGGTCCTGGTGGC  747 CCGCATACAGCCTTGCTTGATGCAGCCAAACTTTATGCCGAAAAAACAGGTATTATAGTGAACGTTCAT TACGGCCCACAGAACAAATGGAATGAAGATGCCAAAAAAAATGCAGATATCTTGTTTGGCGCATCAGAA CAATCTGCTCTGGCTATCATTCGGGACCATAAAGACAGCTTCAGTGAAAAAGATATTCAGCCTCTTTAT CTGCGAAAAAGTATTTTACTGGTAAAGAAAGGTAATCCTAAAAATATCCGGAGTATTGACGACCTGACC AGACCTGGGATTGGCGTAATTGTTAATGATGGTGGTGGTACCAGTAATACATCAGGCACTGGCGTCTGG GAAGATATTGCCGGACGTAAAGGGAATATAGAAACTGTCGCCGCAATCCGAAAAAATATTATTTTATAT GCGCCGAATAGCGGAACTGCACGTAAGGCTCTTGAGAATCAGCCTGGAGCAGATGTCTGGATAACCTGG GCTGACTGGGCAGCCAGTAATCCAGAAATTGGTGATGTCGTGGAAATAGCGCCAGACTACGTGATATGG CGTGATATGAACATTACAGTACGTCAGGATGCAAATGATGAAACCCGTCGATTTGCAGAATGGCTACAA ACCGATGAAGCGGCGCCTGCATTCAAAAAATATGGCTGGACCAGGAAAGGCACTTGA [SEQ ID NO: 4] MC002 MAGFLIFLSSAAYADINLYGPGGPHTALLDAAKLYAEKTGIIVNVHYGPQNKWNEDAKKNADILFGASE  248 prot QSALAIIRDHKDSFSEKDIQPLYLRKSILLVKKGNPKNIRSIDDLTRPGIGVIVNDGGGTSNTSGTGVW EDIAGRKGNIETVAAIRKNIILYAPNSGTARKALENQPGADVWITWADWAASNPEIGDVVEIAPDYVIW RDMNITVRQDANDETRRFAEWLQTDEAAPAFKKYGWTRKGT [SEQ ID NO: 28] MC003 ATGAAATTAAAAATAGTTGCGGTGGTTGTAACTGGTTTGTTAGCTGCGAACGTAGCACACGCTGCCGAA 1101 GTCTATAACAAGGATGGTAATAAACTCGACCTTTATGGCAAGGTTACCGCTCTACGTTATTTTACTGAT GATAAGCGTGACGATGGTGATAAAACTTATGCCCGTCTCGGCTTTAAAGGAGAAACGCAAATCAATGAT CAAATGATTGGTTTTGGTCACTGGGAATATGATTTTAAAGGCTATAACGATGAAGCCAACGGCTCGCGC GACAACAAGACCCGTCTGGCCTATGCTGGTTTAAAAATTAGTGAATTTGGCTCTCTGGACTATGGCCGT AACTACGGTGTCGGCTATGACATTGGTTCATGGACTGATATGTTGCCAGAATTTGGTGGCGATACCTGG AGTCAGAAAGATGTCTTCATGACATACGGTACCACCGGTGTAGCAACCTATCGCAACTACGATTTCTTT GGCTTAATTGAAGGGCTGAACTTTGCCGCGCAATATCAAGGCAAAAATGAACGTACTGACAACAGTCAT CTTTATGGTGCTGACTACACGCGTGCCAACGGTGACGGTTTCGGTATCTCCTCAACTTATGTTTATGAT GGCTTTGGTATCGGAGCGGTGTATACCAAATCCGATCGGACAAATGCGCAGGAAAGAGCCGCTGCTAAT CCTCTCAATGCCTCCGGTAAGAATGCAGAACTGTGGGCTACAGGTATAAAATATGATGCCAACAACATC TACTTTGCAGCTAATTACGCTGAAACATTAAACATGACCACCTATGGCGATGGTTATATTTCTAACAAA GCACAAAGTTTTGAAGTGGTGGCGCAATATCAATTCGACTTCGGCTTGCGCCCCTCACTCGCTTACCTG AAATCGAAAGGCATAGATCTGGGCCGCTACGGCGATCAGGACATGATTGAGTATATCGACGTTGGTGCG ACGTATTTCTTCAACAAAAATATGTCGACCTATGTTGATTATAAAATCAACCTGATTGATGAAAGCGAC TTTACCCGTGCCGTAGATATTCGCACCGATAACATCGTCGCTACGGGCATTACCTATCAGTTCTAA [SEQ ID NO: 5] MC003 MKLKIVAVVVTGLLAANVAHAAEVYNKDGNKLDLYGKVTALRYFTDDKRDDGDKTYARLGFKGETQIND  366 prot QMIGFGHWEYDFKGYNDEANGSRDNKTRLAYAGLKISEFGSLDYGRNYGVGYDIGSWTDMLPEFGGDTW SQKDVFMTYRTTGVATYRNYDFFGLIEGLNFAAQYQGKNERTDNSHLYGADYTRANGDGFGISSTYVYD GFGIGAVYTKSDRTNAQERAAANPLNASGKNAELWATGIKYDANNIYFAANYAETLNMTTYGDGYISNK AQSFEVVAQYQFDFGLRPSLAYLKSKGIDLGRYGDQDMIEYIDVGATYFFNKNMSTYVDYKINLIDESD FTRAVDIRTDNIVATGITYQF [SEQ ID NO: 29] MC004 ATGAAGTGTATATTATTTAAATGGGTACTGTGCCTGTTACTGGGTTTTTCTTCGGTATCCTATTCCCGG  960 GAGTTTACGATAGACTTTTCGACCCAACAAAGTTATGTCTCTTCGTTAAATAGTATACGGACAGAGATA TCGACCCCTCTTGAACATATATCTCAGGGGACCACATCGGTGTCTGTTATTAACCACACCGCACCGGGC AGTTATTTTGCTGTGGATATACGAGGGCTTGATGTCTATCAGGCGCGTTTTGACCATCTTCGTCTGATT ATTGAGCAAAATAATTTATATGTGGCCGGGTTCGTTAATACGGCAACAAATACTTTCTACCGTTTTTCA GATTTTACACATATATCAGTGCCCGGTGTGACAACGGTTTCCATGACAACGGACAGCAGTTATACCACT CTGCAACGTGTCGCAGCGCTGGAACGTTCCGGAATGCAAATCAGTCGTCACTCACTGGTTTCATCATAT CTGGCGTTAATGGAGTTCAGTGGTAATACAATGACCAGAGATGCATCCAGAGCAGTTCTGCGTTTTGTC ACTGTCACAGCAGAAGCCTTACGCTTCAGGCAGATACAGAGAGAATTTCGTCAGGCACTGTCTGAAACT GCTCCTGTGTATACGATGACGCCGGGAGACGTGGACCTCACTCTGAACTGGGGGCGAATCAGCAATGTG CTTCCGGAGTATCGGGGAGAGGATGGTGTCAGAGTGGGGAGAATATCCTTTAATAATATATCAGCGATA CTGGGGACTGTGGCCGTTATACTGAATTGCCATCATCAGGGGGCGCGTTCTGTTCGCGCCGTGAATGAA GAGAGTCAACCAGAATGTCAGATAACTGGCGACAGGCCTGTTATAAAAATAAACAATACATTATGGGAA AGTAATACAGCTGCAGCGTTTCTGAACAGAAAGTCACAGTTTTTATATACAACGGGTAAATAA [SEQ ID NO: 6] MC004 MKCILFKWVLCLLLGFSSVSYSREFTIDFSTQQSYVSSLNSIRTEISTPLEHISQGTTSVSVINHTPPG  319 prot SYFAVDIRGLDVYQARFDHLRLIIEQNNLYVAGFVNTATNTFYRFSDFTHISVPGVTTVSMTTDSSYTT LQRVAALERSGMQISRHSLVSSYLALMEFSGNTMTRDASRAVLRFVTVTAEALRFRQIQREFRQALSET APVYTMTPGDVDLTLNWGRISNVLPEYRGEDGVRVGRISFNNISAILGTVAVILNCHHQGARSVRAVNE ESQPECQITGDRPVIKINNTLWESNTAAAFLNRKSQFLYTTGK [SEQ ID NO: 30] MC005 ATGAAAATAATTATTTTTAGAGTGCTAACTTTTTTCTTTGTTATCTTTTCAGTTAATGTGGTTGCGAAG  948 GAATTTACCTTAGACTTCTCGACTGCAAAGACGTATGTAGATTCGCTGAATGTCATTCGCTCTGCAATA GGTACTCCATTACAGACTATTTCATCAGGAGGTAGGTCTTTACTGATGATTGATAGTGGCACAGGGGAT AATTTGTTTGCAGTTGATGTCAGAGGGATAGATCCAGAGGAAGGGCGGTTTAATAATCTACGGCTTATT GTTGAACGAAATAATTTATATGTGACAGGATTTGTTAACAGGACAAATAATGTTTTTTATCGCTTTGCT GATTTTTCACATGTTACCTTTCCAGGTACAACAGCGGTTACATTGTCTGGTGACAGTAGCTATACCACG TTACAGCGTGTTGGAGGGATCAGTCGTACGGGGATGCAGATAAATCGCCATTCGTTGACTACTTCTTAT CTGGATTTAATGTCGCATAGTGGAACCTCACTGACGCAGTCTGTGGCAAGAGCGATGTTACGGTTTGTT ACTGTGACAGCTGAAGCTTTACGTTTTCGGCAAATACAGAGGGGATTTCGTACAACACTGGATGATCTC AGTGGGCGTTCTTATGTAATGACTGCTGAAGATGTTGATCTTACATTGAACTGGGGAAGGTTGAGTAGT GTCCTGCCTGATTATCATGGACAAGACTCTGTTCGTGTAGGAAGAATTTCTTTTGGAAGCATTAATGCA ATTCTGGGAAGCGTGGCATTAATACTGAATTGTCATCATCATGCATCGCGAGTTGCCAGAATGGCATCT GATGAGTTTCCTTCTATGTGTCCGGCAGATGGAAGAGTCCGTGGGATTACGCACAATAAAATATTGTGG GATTCATCCACTCTGGGGGCAATTCTGATGCGCAGAACTATTAGCAGTTGA [SEQ ID NO: 7] MC005 MKIIIFRVLTFFFVIFSVNVVAKEFTLDFSTAKTYVDSLNVIRSAIGTPLQTISSGGTSLLMIDSGTGD  315 prot NLFAVDVRGIDPEEGRFNNLRLIVERNNLYVTGFVNRTNNVFYRFADFSHVTFPGTTAVTLSGDSSYTT LQRVAGISRTGMQINRHSLTTSYLDLMSHSGTSLTQSVARAMLRFVTVTAEALRFRQIQRGFRTTLDDL SGRSYVMTAEDVDLTLNWGRLSSVLPDYHGQDSVRVGRISFGSINAILGSVALILNCHHHASRVARMAS DEFPSMCPADGRVRGITHNKILWDSSTLGAILMRRTISS [SEQ ID NO: 31] MC006 ATGCAAAGGAAAGGCAATAAACTGTTGATTCAGTTATGCAGTGTGATACTGCTATTTTTTACCACATCC 1110 TGGTATGCATTGGCGAATGAATGTTATATAGAGAGAAATGCTGAAGGGGATTATCACATGAAGATAAGC TCTACTCAGCTTAGTCTGGCGTCACAAATGGTCGAGGTTCCGACAGAAATAGCCGAAGCTACATGGGAT GTAAATATTCAACTAAGAGGCGATGCCATAGGGTGTAAATCTCTTGGGGATAGTAAGGCAGTTCACTTT CTTAATACAGCTGACCCAAGTTTAATATCCACGTACACCACAACGAATGGCGCAGCGTTATTAAAAACA ACTGTTCCAGGCATTGTGTATTCTGTCGAGTTATTATGCCTTAGTTGTGGTGCCGCAGATGAACTTGAT TTATGGCTACCTGCACAAAGTGGCGCAGATAACTTCATACCAAGCACCCAGACGAAATGGGCCTATGAG TACAGTGATCAAAGTTGGTATTTACGTTTTCGCTTATTCATAACTCCTGAATTTAAACCCAAGAATGGT GTTTCCAGCGGAACAACGATAGCAGGAAAGATTGCGTCATGGTATATAGGTACCAATGACCAGCCGTGG ATCAACTTTTACATTGACAATGACTCTTTAAAGTTTTTCGTCGATGAACCGACCTGTGCAACAGTTGCC CTGGCACAAGATCAGGGCAACGTCAGTGGCAATCAGGTAACGCTTGGGAACAGCTATGTTTCGGAAGTG AAAAATGGGCTTACGCGGGAAATCCCTTTTTCTATCCGTGCTGAATACTGTTATGCCAGTAAAATTACG GTTAAGTTGAAAGCGGCAAATAAACCCAGCGATGCCACACTGGTGGGTAAAACGACTGGCTCGGCTTCA GGCGTGGCTGTAAAAGTAAATTCAACTTATGACAATAGCAAAGTATTGTTAAAAGCAGATGGTAGCAAC ACGGTTGACTACAACTTCGCCGCCTGGTCAAACAACCTGCTGTTTTTACCTTTTACGGCGCAGCTGGTA CCGGATGGTAGCGGTAATGCTGTCGGTGTTGGAACATTTTCAGGTAACGCGACCTTCTCCTTTACCTAC GAATAA [SEQ ID NO: 8] MC006 MQRKGNKLLIQLCSVILLFFTTSWYALANECYIERNAEGDYHMKISSTQLSLASQMVEVPTEIAEATWD  369 prot VNIQLRGDAIGCKSLGDSKAVHFLNTADPSLISTYTTTNGAALLKTTVPGIVYSVELLCLSCGAADELD LWLPAQSGADNFIPSTQTKWAYEYSDQSWYLRFRLFITPEFKPKNGVSSGTTIAGKIASWYIGTNDQPW INFYIDNDSLKFFVDEPTCATVALAQDQGNVSGNQVTLGNSYVSEVKNGLTREIPFSIRAEYCYASKIT VKLKAANKPSDATLVGKTTGSASGVAVKVNSTYDNSKVLLKADGSNTVDYNFAAWSNNLLFLPFTAQLV PDGSGNAVGVGTFSGNATFSFTYE [SEQ ID NO: 32] MC008 ATGAGATTCGCCAAAGGCGTGTTGCTCGCCATCTGTCTGATTTTTTTGCCGCTAAAAGCGGCGCTGGCG 1062 CTGAACTGCTATTTTGGTACCGCAAACGGCGCTGTAGAAAAATCGGAAGCTATTATGCCCTTCGCCGTT CCGGCCAATTCCAAACCCGGCGATAAAATCTGGGAATCTGACGATATAAAAATTCCGGTCTACTGTGAC AACAACACAAACGGTAATTTTGAAAGCGAGCACGTCTACGCCTGGGTAAACCCTTACCCCGGTATTCAG GATCCCTATTATCAATTGGGCGTAACCTATGAAGGCGTGGACTATGACGCAAGCCTTGGGAAAAGCCGC ATCGAGACGAATCAGTGCATCGACAGTAAGAATATTGATATTTAGACCCCGGAGCAGATCATTGCGATG GGCTGGCAAAATAAACTTTGCTCCGGCGATGCAACCGTTATGCACAAATCGCGGACGTTTGTGGCGCGT ATGCGGCTTTACGTTAAAGTTCGCGCCATGCCGCCCCATGATTATCAGAGCAAACTCAGCGATTACATC GTCGTACAGTTTGATGGCGCAGGCAGCGTGAACGAAGACCCTACCGCGAAGAATCTGAAATATCACATT ACCGGTCTGGAAAATATCCGCGTGCTGGATTGCAGCGTCAACTTTGCTATCTCACCTGAAACCCAGGTC GTTGATTTTGGCCGATTTAACGTGCTGGATATTCGTCGCCATACGATGTCGCAGCAATTTAAAATAACT ACAACCAAATCACAAAACGACCAGTGTACCGACGGTTTTAAAGTCAGCTCTTCGTTTTATACCGATGAA ACCCTTATCGACGAAGATAAATCACTGCTCATTGGCAATGGCTTGAAGCTTCGATTGTTGGATGAAAAT GCCTCACCCTATACTTTCAACAAATACAGTGAGTATGCCGATTTTACCAGCGACCTGTTAGTGTATGAA AAAAGCTACACGGCAGAATTGTCATCCACGCCGGGTACGCCCATCGACGTTGGTCCCTTTGATACAGTG GTACTTTTCAAAATTAACTACAACTGA [SEQ ID NO: 9] MC008 MRFAKGVLLAICLIFLPLKAALALNCYFGTANGAVEKSEAIMPFAVPANSKPGDKIWESDDIKIPVYCD  353 prot NNTNGNFESEHVYAWVNPYPGIQDPYYQLGVTYEGVDYDASLGKSRIDTNQCIDSKNIDIYTPEQIIAM GWQNKLCSGDPTVMHKSRTFVARMRLYVKVRAMPPHDYQSKLSDYIVVQFDGAGSVNEDPTAKNLKYHI TGLENIRVLDCSVNFAISPETQVVDFGRFNVLDIRRHTMSQQFKITTTKSQNDQCTDGFKVSSSFYTDE TLIDEDKSLLIGNGLKLRLLDENASPYTFNKYSEYADFTSDLLVYEKTYTAELSSTPGTPIDVGPFDTV VLFKINYN [SEQ ID NO: 33] MC009 TTGTGGGAATGTGATGCAACAGATTTGCCAAACATCTATTTTCTGGTCGCTACCAATGGCGACGACCGC 1086 GTGGGGGGCTTTTACGATGGAGGCGGGCCTGATGGTCTGAGTGATGTCTATGCCACCTGGTTGGCTTTT GTCGGTCTCAAGCAGACCATGGCGGGCGTGACGCTTGGTCGTTACTGGAAGAAAGTGCCCATCACCAGT TATGCCACTCAGGGAACTAAAATCCAGATTCGCTTACAGGATATCCCTCCTCTTCATGCTGAGCTTTAT CGCATCAGTACGCTACCTGATACATCAGCAACAACAAGTTGGTGCGGTAATAATAATACAGATAGTAGT GGAGTCGGATTCGCAAAACCTTCCGGTACAATCTATAACTGTGTTCAGCCCAATGCCTATATTCAGCTT TCCGGTACCAGCGGCATTTTATTTGGTCATGATGAGCCCGGCGAAGATAGTTCTGTTCATTGGGATTTC TGGGGTGCTGATAATGGTTTTGGTTACGGAATGCGTTCGGCCAATCGACTCTACAACAATGCCACCTGC GTTGCCCGCAGCGCCACGCCGTTAGTATTGCTGCCGACAATTGCAGAAGCACAACTGAATGCGGGCATG GAAAGTACCGGTAATTTTAATGTCCGCGTCGAGTGTAGTAACTCGGTTCAATCAGGGATTAGCGATACT CAGACAGCATTAGGAATCCAGGTGTCTGAAGGTGCATATACAGCGGCGCAAAAACTGGGGATTATCAAT AGCAACGGCGGCGTCAGCGCCCTGGTCTCTGATAATTATGACGCAGCAGAGATGGCAAAGGGCGTTGGG ATCTACATTTCTAACAGTGCTCACCCCGATACGGCGATGACGCTGGTTGGTCAACCGGGCATCGCGAAG TTAACCCCCGGAGGAAATGCAGCGGGGTGGTATCCTGTATTTGAAGGGGCAACATTAGAAGGTGCGACT CACCCCGGATACTCCAGCTATAGTTACTCTTTTATCGCCCGGTTGAAGAAACTGCCAAATCAGACAGTC AGTGCGGGAAAAGTGCGGGCAACGGCTTATATATTGGTGAAAATGCAATGA [SEQ ID NO: 10] MC009 MWECDATDLPNIYFLVATNGDDRVGGFYDAGGPDGLSDVYATWFAFVGLKQTMAGVTLGRYWKKVPITS  361 prot YATQGTKIQIRLQDIPPLHAELYRISTLPDTSATTSWCGNNNTDSSGVGFAKPSGTIYNCNQPNAYIQL SGTSGILFGHDEPGEDSSVHWDFWGADNGFGYGMRSANRLYNNATCVARSATPLVLLPTIAEAQLNAGM ESTGNFNVRVECSNSVQSGISDTQTALGIQVSEGAYTAAQKLGIINSNGGVSALVSDNYDAAEMAKGVG IYISNSAHPDTAMTLVGQPGIAKLTPGGNAAGWYPVFEGATLEGATHPGYSSYSYSFIARLKKLPNQTV SAGKVRATAYILVKMQ [SEQ ID NO: 34] MC010 ATGAATATGGCTTTTTACGGCAAGTGGTTTGCTTGCCTGTGGCTCGCTACGTCGTGCGTTCAGGCGGCG  789 AGCACAGATAATAAGGCGCTGGAGATAATTCGTCGCGCTGACGAAATTCGTTCGCCGAATAAACCGTTT CGTTAGACGCTGACGGTAACGGAATATAAAGCGGGCGCAACCCAGCCAGAGAATAAACAGGTCCTCGAT ATTTCCATGCGCTTTATGAAACCGCAGGGTAATGAAAAAGCGGATGCACGCTCGCTGGTGCGTTTTATT TATCCGCCGCGAGATAAAGGAAAAATCATGCTTTCCGACTGGTACGATTTATGGTTTTACACGCCGGAA CTGCGACGTCCTATGCCTATTTCACGGCAACAAAGATTAATTGGGCAAATCTCTAATGGCGATGTCAT7 GTCACTAACTTTGAATATGCCTATGACTCGACCCTGATGGGGGAAGTCACGTGTGCTGAAAAGCAGTGT TACAAGCTGGCGCTGGTGCGTAAATCGGCGGATATCACCTGGCCGAAGGTTATCTATTACGTTGAAAAA GACGGTGATAATCGCCCGTGGAAGGCGGCCTATTATTCGCAGGATGACCAGTTAATAAAAGAAGTGTTG TATCAGGATTTCCAGCCGGTGTTGGGGAAAACGCGACCCATGAAAATAACCGTTACCGATGTTCGTCAC GGCAATAACTATTCAGTGATGGAGTACAGCGATGTTCGTCTGGAATCGCTGCCGGAGTTTCATTTCACC AAAGAGTATATTCAGCGAGGTGCGAAATGA [SEQ ID NO: 11] MC010 MNMAFYGKWFACLWLATSCVQAASTDNKALEIIRRADEIRSPNKPFRYTLTVTEYKAGATQPENKQVLD  262 prot ISMRFMKPQGNEKADARSLVRFIYPPRDKGKIMLSDWYDLWFYTPELRRPMPISRQQRLIGQISNGDVI VTNFEYAYDSTLMGEVTCAEKQCYKLALVRKSADITWPKVIYYVEKDGDNRPWKAAYYDQDDQLIKEVL YQDFQPVLGKTRPMKITVTDVRHGNNYSVMEYSDVRLESLPEFHFTKEYIQRGAK [SEQ ID NO: 35] MC011 ATGAAACGTACGCTGAAGATCTCTTCGTTGCTGTGTGTTGCGCTGCCGTTGACGGTACAGGCGGATTGC 1389 CTGTCAGGTGACGAGGTGGCACAAAATAGCGATGTGACGCTTTACGAGCAGGTGTCTTATGTCAATAAA CAGGCTTCGGCCTGGCAGATTGCAGGCAAAAATCCCTACACCCGTCACAACGGTTATCAGGAGGCGGGG ATTGGCATCAATAGCGGTTGTTCGATAATCGACAATACGCTGGACCTTAAGCTCAATCTGTATGGAATA AACGAATATGCGCTTAAACCCGCAGGGAAATTCGAAACGGATGATAGCCGCACGCGTGCGTTAATTAAC CGCCTCAGTCTGGTCTATAGCGCCTCGGACAGCGTTCAATTTGAAGCAGGCAAATTTGCCGCGCCGTCA GGAATGTTCTTTTTGCGTTCGCCTTCTGATTTGCAAACGCATTATTACACCGGATTCCAGTCGACGCGT TTGCACGATCCCAAAATGACATCGGCGTATCAGGCGTCATCGTGGGGCGCAAAAATGAGCGTGGATACA CGCGATTATGCGTTTTCGGCGAGTGTCATACCGAAGTTAGCCACCATCGACAAACGCTATGTGACGTCT GGCAACTGGTCGGCTAATCAGCAGGGAAACAGCGACGAAGCCTATCTGCTGAGCTTCAGCGATCATCGC TTTGGTGAGCACACGCCGACAGTCAATGTGCGGCTCGGACCATCGCCGTCACTCGCGCTGTCTGACAGT TATCACTACACCCCGCAGCTTACGCTGAATGTCGACGCAGCCTACCACCGCTCCCAGCAATGGCGGCAT CTTTCCCACCGTGAGACGGCGCAGGTCGAGGAATATCAGTTTCCGGATTCGCTCTATGAAACGAAAGAT GAAAGCGGCGTAGAGCTGGCGCTGGGTGGGGAGTACACCAGTGATAATTTCAGCGTGTTTGGCGTTGAG TATTACTTTCAGAGCGAGGGTTATTCGCGCGCTGAACAGCGTCAGCAGCGCGAGTTAATTGACTTCCTC AATACCACAACCGGCTATGCGCCACTGGATCAGGCATTTGATTCTTACAAATACCTGATGGCTTCAGAA ATCAGCAATACCGCCAATCAGGGGATGCTGCAGGGTAAGCACTATCTGAACGCCTGGGCCAGTCTGCCG CTGGCGGGAGAGTCGACGCTGCAGCCTTCGCTGGTGGTGAATCTCGTTGATGGCAGCACGTTGCTGGGC CTGCATTATTCCACGCCGCTCAGCGCTATAAGTAACCAGCTTGAAGCCTATGCCGGTGGCTATAGCGCG CTGGGAAGTCGGTACTCCGAATTTGCGCTTTTTGGCGACACGTTAGGCCTTTATTTGGGCTTTAAATAC TATCTATAA [SEQ ID NO: 12] MC011 MKRTLKISSLLCVALPLTVQADCLSGDEVAQNSDVTLYEQVSYVNKQASAWQIAGKNPYTRHNGYQEAG  462 prot IGINSGCSIIDNTLDLKLNLYGINEYALKPAGKFETDDSRTRALINRLSLVYSASDSVQFEAGKFAAPS FMFFLRSPSDLQTHYYTGFQSTRLHDPKMTSAYQASSWGAKMSVDTRDYAFSASVIPKLATIDKRYVTS GNWSANQQGNSDEAYLLSFSDHRFGEHTPTVNVRLGPSPSLALSDSYHYTPQLTLNVDAAYHRSQQWRH LSHRETAQVEEYQFPDSLYETKDESGVELALGGQYTSDNFSVFGVEYYFQSEGYSRAEQRQQRELIDFL NTTTGYAPLDQAFDSYKYLMASEISNTANQGMLQGKHYLNAWASLPLAGESTLQPSLVVNLVDGSTLLG LHYSTPLSAISNQLEAYAGGYSALGSRYSEFALFGDTLGLYLGFKYYL [SEQ ID NO: 36] MC012 GTGGGGATCGACAGCCGTAATGATATTCCTGAGGGGATTGCGACGCTGGGCGCTTTTATGGGTTATTCC  705 CATTCACATATCGGTTTTGATCGTGGAGGACATGGCAGTGTGGACAGTTATTCTCTGGGCGGCTATGCC AGTTGGGAACATGAAAGTGGTTTCTATCTGGACGGTGTCGTGAAGCTGAACCGTTTTGAAAGTAACGTA GCCGGTAAAATGAGCAGCGGTGGAGCCGCCAATGGCAGTTACCATAGCAACGGGCTGGGCGGTCACATT GAAACCGGGATGCGATTTACCGATGGTAACTGGAACCTGACGCCGTATGCCTCGTTAACGGGGTTCACC GCTGATAACCCCGAATATCATTTATCCAATGGCATGGAATCGAAATCAGTCGATACCCGCAGTATATAT CGTGAACTGGGTGCAACGCTGAGTTACAACATGCGTCTGGGGAACGGTATGGAAGTTGAGCCGTGGCTG AAGGCGGCTGTGCGCAAAGAATTTGTCGATGATAACCGGGTGAAAGTGAATAGTGACGGTAATTTCGTC AATGATTTGTCGGGCAGACGTGGAATATACCAGGCAGGTATTAAAGCCTCATTCAGCAGTACGTTAAGC GGGCATCTTGGGGTGGGGTATAGCAACGGTGCTGGTATGGAATCCCCGTGGAACGCGGTGGCTGGTGTG AACTGGTCGTTCTGA [SEQ ID NO: 13] MC012 MGIDSRNDIPEGIATLGAFMGYSHSHIGFDRGGHGSVDSYSLGGYASWEHESGFYLDGVVKLNRFESNV  234 prot AGKMSSGGAANGSYHSNGLGGHIETGMRFTDGNWNLTPYASLTGFTADNPEYHLSNGMESKSVDTRSIY RELGATLSYNMRLGNGMEVEPWLKAAVRKEFVDDNRVKVNSDGNFVNDLSGRRGIYQAGIKASFSSTLS GHLGVGYSNGAGMESPWNAVAGVNWSF [SEQ ID NO: 37] MC013 ATGAAATTCCCTTCAATATTTAACAAAATAAAACCACAATCCATACAGCAACATCCAGAAAAAAATCAA 1260 CTTAACTGGATGCTCGAATTAAATAAATGGAAAGAAGAACGTATACTTACAGGTGAAATCCATCGTCCG GAATGTCGAAACGAAGCCGCTAAAAGGATAAACTGTGCTTTTTTGTCGAAACAGAATGACATTGATTTA TCAGGACTTAATTTATCTACTCAACCACCAGGGCTGCAAAACTTCACCTCTATCAATCTTGATAATAAC CAACTCACACATTTTGATGCAACCAACTACGATAGACTCGTAAAACTTAGTCTGAATAGTAACACTCTT GAGTCAATAAATATTCATCAAGGCAGAAATGTAAGCATTACACATATATCTATGAATAATAATTGTCTC AGAAATATTGATATAGATAGGCTTTCATCAATTACTTATTTTAGTGCGGCACATAATAAACTAGAGTTT GTGCAATTAGAATCTTGCGAATGGCTGCAATACCTGAATCTCAGCCATAATCAATTAACTGATATTGTT ACAGGAAATAAAGAAGAACTCTTACTGCTGGATCTATCCCATAATAAACTAGCAAGTTTACACAATGCC TTATTTCCCAACTTAAATACGTTACTTATCAACAACAACTTGCTTTCTGAAATTAAAATGTTTTATAGC AACTTCTGCAAAGTTCAGACATTAAACGCTGCTAACAATCAGTTGGAAAAAATAAACCTTCATTTCCTG ACTTATCTTTCATCTATCAAAAGTTTAAGGCTGGACAATAATAAAATAACTCGCATTGATACTGAGAAC ACATCCGATATTAGAAGTTTATTCCCCATAATAAAGAAGAGCGAAAGCTTAAATTTTTTAAATATTTCT GGCGAGAACAATTGCCCTACTATCCAGCTCATGTTATTTAATTTGTTTTCCCCAGCACTTAAGCTTAAT ACTGGCCTGGCAATTCTTTCGCCTGGTGCATTTGAAGATCACTCTGACGGATTAGATGTGGATAACGAA TTGTTTCACTATACTATTAATAAAGCATATACCCCATATAATATACATACTTATAAAACAGAAGAAGTT GTAAACCAGAGGAATATAAAAATTAAAAATATGACCTTAGATGAAATAAACAATACTTATTGTAATAAC GATTATTACAATGAGGCAATAAGAGAGGAACCGATAGACTTTCTGGACAGATCGTTTTCCTCCAGCTCA TGGCCTTTTTATCACTAA [SEQ ID NO: 14] MC013 MKFPSIFNKIKPQSIQQHPEKNQLNWMLELNKWKEERILTGEIHRPECRNEAAKRINCAFLSKQNDIDL  419 prot SGLNLSTQPPGLQNFTSINLDNNQLTHFDATNYDRLVKLSLNSNTLESINIHQGRNVSITHISMGGGCL RNIDIDRLSSITYFSAAHNKLEFVQLESCEWLQYLNLSHNQLTDIVTGNKEELLLLDLSHNKLASLHNA LFPNLNTLLINNNLLSEIKMFYSNFCKVQTLNAANNQLEKINLHFLTYLSSIKSLRLDNNKITRIDTEN TSDIRSLFPIIKKSESLNFLNISGENNCPTIQLMLFNLFSPALKLNTGLAILSPGAFEDHSDGLDVDNE LFHYTINKAYTPYNIHTYKTEEVVNQRNIKIKNMTLDEINNTYCNNDYYNEAIREEPIDFLDRSFSSSS WPFYH [SEQ ID NO: 38] MC014 GTGAACAAGGCCCCCTCTTTAATTGCCGCTATCGTCCTCGGACTGGGGATTAGCGCCTGTGGTTATTTT  711 GTTGGCGATGGTGTTAAACATTTAAAAACCAACAACCGTTATGTCAATGTGCGCGGGCTTTCTGAAAAA GAAGTTCGCGCAGATACGGCGGAATTAAGAATTGCGATTAACTTTAAGGGTAATGTTCCCGGCGAACTG TTCCCGAAACTGGAAGAAGCGCAGAAAAAAATTGTTGCCGAACTCAATGCTCAGGGGATTAACGAGAAA GAGATAATTCTGGGCCAATGGACAAGCAAGCGAACAGATTCCTTTTATCTGAAAGATGATCCCACAATG CCACGCTATAACGCAGACGGGTCAGTGACGATAAAAACCCATAATGTTGCTGCTGTCGAAAAAGTCGTC GCGAAATTAAACGAACTGCAAGTCGCTACGGATGGCGCTATCGCTGAGAGCAAAGTCGCCTATCGCTTT AATGGTATTGGCGCACTGCGCGCTGAGATGATTGCTGCCGCCACCAAAGATGCACGCAACGCCGCACTA CAATTTGCAACGGACTCAGGTAGCCAGGTGGGGTCAATTAGCGATGCCTCACAAGGCGTATTCCAGATC TTTGCCAGTGGCAGTGATGAAGATGATCCTACGGCGATTAATAAAACGGTACGCGTAGTCACGACCGTA ACCTATGCGTTGCAGGATTAA [SEQ ID NO: 15] MC014 MNKAPSLIAAIVLGLGISACGYFVGDGVKHLKTNNRYVNVRGLSEKEVRADTAELTIAINFKGNVPGEL  236 prot FPKLEEAQKKIVAELNAQGINEKEIILGQWTSKRTDSFYLKDDPTMPRYNADGSVTIKTHNVAAVEKVV AKLNELQVATDGAIAESKVAYRFNGIGALRAEMIAAATKDARNAALQFATDSGSQVGSISDASQGVFQI FASGSDEDDPTAINKTVRVVTTVTYALQD [SEQ ID NO: 39] MC015 ATGAAAAAATGGACGATATTTTTGACAAGTCTGATATTACTTGCTCTCAGTTTAGAAACACCAAAGTGC  843 TATGCCGGTGATAAACTCATGAGTGCAAGCTTTTCCAGTACTAAAATTTATTATGCGATGAAAAACGTT ACTGCTTCCGGCAGTTTATATTTCTATGTCACGGTAGTGACGCCGGGAGAAGTAAGCTACGGACAATAC AACTCCAATGCAAGAAAAGGCGACACCCTCAAGTTAATATCCTGGAGCGGATCTGGCCCGGCACCGACA CTGGTTTTGACTGATTATAGACGTACGGACACCTCAAATTGCCCTGGTATCAATACTCGTGTCTTTGTC TGTGCATATATGACTTTTAACGTCACTGTAGAATCTGATAATTATGGTTGTCCGTGGATTGCCTCATTT TATTGAGTATCTGAGGCATTTGGATTTGGTAGGTATACAAGCCGAACAGTTCATGATTCTATTTGGCCG ACAATTCCCGTCGCTTCGTTTGATATATCCTGGAGTGATAATTATGTTAGCCATAATAAAGCGCTGCGA TTGCAATCCGATGGTTCGACAATCACGACTACGCTTTCGACCTACCTGATGGAAAGCGGCAAACTCTGC GATGGCAGTATTTTTGATTCCAGAGGGGCATATTGTCGTGCTGTTTCTGACTTATTAACCTTTACCTCG TATGGTTGTGATAATGCAAAGGTGACAGTCACCCCCTCACGTCAACCATTGACGGATAGAAAGCTACAC GACATTGTGGTACAGGTGAATACCAGTAGCCGTGAGCCAATTGATTCTACATGCCGTTTCCAGTATGTA CTGAATGAACTGTAG [SEQ ID NO: 16] MC015 MKKWTIFLTSLILLALSLETPKCYAGDKLMSASFSSTKIYYAMKNVTASGSLYFYVTVVTPGEVSYGQY  280 prot NSNARKGDTLKLISWSGSGPAPTLVLTDYRRTDTSNCPGINTRVFVCAYMTFNVTVESDNYGCPWIASF YSVSEAFGFGTYTSPTVHDSICPTIPVASFDISWSDNYVSHNKALRLQSDGSTITTTLSTYLMESGKLC DGSIFDSRGAYCRAVSDLLTFTSYGCDNAKVTVTPSRQPLTDRKLHDIVVQVNTSSREPIDSTCRFQYV LNEL [SEQ ID NO: 40] MC016 ATGGGTACAGCAGCTATAAGTCATTTACGATATGATCTTAACAAATATGCCCTTTCTTTACGCAAAACC  912 GCAACACTTGCTTCAACATTTTTTATTGAGTCCCCATTAGTTAGATTCGAGTATCTGCAAGAAATAGAA AATACTATTAATGATATTACTCACAGATTCAATTCTTCATATGACATCAATGAAAAAGCACGACTTATC AATGAATTAAAAATGGAGTCAGAAACAGCAAGAAAAGAATATCAACTTTTCAGACAAGGAAATTATGAT AAATATATCACTACTGATATTTTCGAAGAACATGGTTTGATAAAATATGTGAACTTAAGTTTGGATATT GTTGCATCTGTAGGAGAGGTCGTAGGCGGGGTTGGCGCGTTGAAATTTGGTAAGGTAGTGCATTCAAAC CGAATAAAAGGTATAGGCGTCACATTAGTTGCTCATGGGGCGAATAATTTTTATGAAAGCTTATCACCT TTATTTTTTAACGAGTATGATTCAGGTCCAATACGTGAACTCTACAGAGTAATAGCAAAAAAAATGGGA GGTGATATTAATTCTGCTGATTATGCATACAGCATCGTGGACTTTTCGATTACTGCATATGGTGGATAT TCAGGCATGAAAATCGTACCTAAGTATAATAGATTGATTCGTCCTTCATTAGGAAATAGACCTGGTACA GGACGATTATTTCATTACACATCAGTTGATTTTAAAAATAAATTCTCATTAAAACCTACCCCTTTAAAA ATCATACAAATTAGTTCTACTGTAAAAAAATTCAAGGTTACATTTTATGATGAAAATACAAATTTGAGG ATAAAACATGGCCTCAATAATCATATGCCACATCAATTATTAATGAATATATCAGGAACTACAACTGGT GCAGGAATACAATAA [SEQ ID NO: 17] MC016 MGTAAISHLRYDLNKYALSLRKTATLASTFFIESPLVRFEYLQEIENTINDITHRFNSSYDINEKARLI  303 prot NELKMESETARKEYQLFRQGNYDKYITTDIFEEHGLIKYVNLSFDIVASVGQVVGGVGALKFGKVVHSN RIKGIGVTLVAHGANNFYESLSPLFFNEYDSGPIRELYRVIAKKMGGDINSADYAYSIVDFSITAYGGY SGMKIVPKYNRLIRPSLGNRPGTGRLFHYTSVDFKNKFSLKPTPLKIIQISSTVKKFKVTFYDENTNLR IKHGLNNHMPHQLLMNISGTTTGAGIQ [SEQ ID NO: 41] MC017 TTGCTGTCACTGACACTGATGTCTGCTTTATTATCGCCTTTATCTCTTCAGGCAGCGGATGTCCGGCGT 1065 AGCGGAGATGAAGCATTTATCATTCAGCAGCAGCGTCAGGAAGCCCTTGAGCAACAACTGACGCCTTCA GCCCCTGATGTTCGCCTTTCTGCACCTGGCTCTTTTGCCCATAAGATTAATTTTCCTGTTGAAACGCCC TGTTTTCAGATTAAACAGACGGAACTGAAGGGGGCTGATGCGTTACCACACTGGCTGCCTTTACAAAAA ATCGCCAACGGGGCGGTCGGGCATTGCCTGGGGGCGAAAGGAATTAATCTGCTGATGAGTACATTGCAG AACCGTCTGGTCGATCATGGTTATGTCACCACCCGTGTTCTGGCACCTTCGCAGGATTTAAAAAGCGGT ATCCTCCGGCTGGTTATTATTCCCGGTGTTGTGCGACATGTGCGTCTGACACCGGACAGTGATGACTAT ATTCAGTTGTATTCCTCATTCCCGGCACACGAAGGTTCTCTGCTGGATTTACGGGACATTGAGCAGGGG GTGGATTTAGGTAACAGCCGGATACAGGGACAACATACTGAGCTGAATGCAACCAGTGGAAATCTGTCT ACACAGAATGCGCAACTGAGTGCCGATACGCTTTCCGCCCGGACTGCCGGGCAGTTCAGCAGTAATGGC GGTACGATAAATGCCGACACACTGCAGATATCGGCACAAAGCCTGTCAAATCGTAAAGGCAGTCTGATT CAGACGGGAACAGGGGATTTTTCGCTGAGTCTGCCGGGAAGCGTGGATAACCGGGAAGGGCTGCTTGCG GCAAATGGCGCGGTGCGTCTGGATGCACTGAGCCTTGATAATCGCAAGGGGAAAGTGCAGGCGGAGCAG TCACCCTCCCTTCAGAAATCCCCGCCCACGTTTCTGAAACCGTTTGTGGCTGGTGTCTGTGCGGCATTG CTGGCGGTCAGCGTGGCTATTCCGGGATGGCAGTTTCTGACACAGCCATCACCGGAGGAGCAGCATTTT ACCTGGGGGAATGGTTGTAAAAAGCAGTGA [SEQ ID NO: 18] MC017 MLSLTLMSALLSPLSLQAADVRRSGDEAFIIQQQRQEALEQQLTPSAPDVRLSAPGSFAHKINFPVETP  354 prot CFQIKQTELKGADALPHWLPLQKIANGAVGHCLGAKGINLLMSTLQNRLVDHGYVTTRVLAPSQDLKSG ILRLVIIPGVVRHVRLTPDSDDYIQLYSSFPAHEGSLLDLRDIEQGLDLGNSRIQGQHTELNATSGNLS TQNAQLSADTLSARTAGQFSSNGGTINADTLQISAQSLSNRKGSLIQTGTGDFSLSLPGSVDNREGLLA ANGAVRLDALSLDNRKGKVQAEQSPSLQKSPPTFLKPFVAGVCAALLAVSVAIPGWQFLTQPSPEEQHF TWGNGCKKQ [SEQ ID NO: 42] MC018 ATGAGCGGAAAACCGGCGGCGCGTCAGGGCGACATGACGCAGTATGGCGGTAGCATTGTTCAGGGTTCA 4200 GCCGGGGTGCGCATTGGTGCCCCCACCGGCGTGGCCTGTTCGGTGTGCCCCGGCGGAGTGACGTCCGGC CATCCGGTCAATCCCCTGCTCGGTGCAAAGGTCCTTCCCGGTGAAACCGACATCGCCCTGCCCGGCCCG CTGCCGTTCATCCTCTCCCGCACCTACAGCAGTTACCGGACAAAAACGCCCGCGCCGGTGGGGAGCCTC GGCCCCGGCTGGAAAATGCCTGCGGATATCCGCTTACAGCTGCGCGATAACACACTGATACTCAGTGAT AACGGCGGCAGAAGCCTGTATTTTGAGCACCTGTTTCCCGGTGAGGACGGTTACAGCCGCAGCGAGTCA CTCTGGCTGGTGCGCGGCGGCGTGGCGAAACTGGATGAAGGTCACCGGCTGGCCGCACTCTGGCAGGCG CTGCCGGAAGAACTCCGCTTAAGTCCGCATCGTTATCTGGCGACAAACAGTCCGCAGGGGCCGTGGTGG CTGCTCGGCTGGTGTGAGCGGGTGCCGGAAGCGGATGAGGTGCTGCCTGCGCCGCTGCGGCCGTACCGG GTACTGACCGGGCTGGTGGACCGCTTCGGGCGCACACAGACGTTCCACCGCGAAGCCGCCGGTGAATTC AGCGGCGAAATCACCGGCGTGACGGATGGTGCCGGGCGTCACTTCCGGCTGGTACTGACCACGCAGGCG CAGCGGGCAGAAGAAGCCCGGCAGCAGGCCATTTCCGGCGGGACGGAACCGTCCGCTTTTCCTGATACC CTGCCGGGTTACACCGAATATGGCCGGGACAACGGCATCCGTCTGTCTGCCGTGTGGCTGACGCACGAC CCGGAATACCCGGAGAATTTACCTGCCGCGCCGCTGGTGCGCTATGGCTGGACGCCGCGCGGCGAACTG GCGGTGGTGTATGACCGTAGTGGCAAACAGGTGCGCAGCTTTACTTACGATGATAAATACCGGGGCCGG ATGGTGGCGCACCGTCACACGGGCCGGCCGGAAATCGGTTACCGTTACGACAGCGACGGGCGGGTGACA GAACAGCTAAACCCGGCAGGCTTAAGCTACACGTATCAGTATGAGAAAGACCGCATCACCATCACCGAC AGCCTGAACCGCCGTGAAGTCCTGCACACGCAGGGTGAAGGCGGGCTGAAGCGGGTGGTGAAAAAGGAA CACGCGGACGGCAGCGTCACGCAGAGTCAGTTTGACGCGGTGGGCAGGCTCAGGGCACAGACGGATGCC GCAGGCAGGACAACAGAATACAGCCCGGATGTGGTGACGGGCCTCATCACGCGCATCACCACGCCGGAT GGCAGGGCATCGGCGTTTTACTATAACCACCACAGCCAGTTAACGTCAGCCACCGGGCCTGACGGGCTG GAAATACGCCGGGAATATGATGAATGGGGCCGTCTGATTCAGGAAACTGCCCCTGACGGCGATATCACC CGCTACCGTTATGATAATCCACACAGTGACTTACCCTGCGCAACGGAAGATGCCACCGGCAGCCGGAAA ACCATGACGTGGAGCCGTTACGGTCAGTTGCTGAGCTTCACCGACTGTTCCGGTTATGTAACCCGTTAT GACCATGACCGCTTCGGGCAGATGACGGCGGTGCACCGCGAGGAAGGGCTGAGTCAGTACCGCGCATAC GACAGCCGTGGACAGTTAATTGCCGTGAAAGAGACGCAGGGCCATGAAACGCGGTATGAATACAACGCC GCCGGTGACCTGACCACCGTCATTGCCCCGGACGGCAGCAGAAACGGGACACAGTACGATGCGTGGGGA AAAGCCATCTGTACCACGCAGGGCGGTCTGACGCGCAGTATGGAATACGATGCTGCCGGACGGGTCATC CGCCTGACCAGTGAAAACGGCAGCCACACCACCTTCCGTTACGATGTACTCGACCGGCTGATACAGGAA ACCGGCTTTGACGGCCGCACACAGCGTTATCACCACGACCTGACCGGCAAACTTATCCGCAGCGAGGAT GAGGGGCTGGTCACCCACTGGCACTATGACGAAGGAGACCGCCTCACGCACCGCACCGTGAAGGGTGAA ACCGCAGAGCGCTGGCAGTATGACGAACGCGGCTGGCTGACAGACATCAGCCATATCAGCGAAGGGCAC CGGGTGACGGTGCATTACGGGTATGATGAGAAAGGCCGGCTGACCGGTGAGCGTCAGACGGTGCATCAC CCGCAGACGGAAGCACTGCTCTGGCAGCATGAGACCAGACACGCTTACAACGCGCAGGGGCTGGCGAAC CGCTGTATACCGGACAGCCTGCCCGCCGTGGAATGGCTGACCTATGGCAGCGGCTGGCTGGCAGGCATG AAGCTCGGCGACACACCGCTGGTGGATTTCACGCGCGACCGCCTGCACCGGAAAACGCTGCGCAGATTC GGCCGTTATGAACTCACCACCGCTTATACCCCTGCCGGGCAGTTACAGAGCCAGCACCTGAACAGCCTG CAGTATGACCGCGATTACACCTGGAACGACAACGGCGAACTCATCCGCATCAGCAGCCCGCGCCAGACC CGGAGTTACAGCTACAGCGACTCCGGCAGGCTGACCGGCGTTCACACCACCGCAGCGAATCTGGATATC CGCATCCCGTATGCCACGGACCCGGCAGGTAACCGCCTGCCCGACCCGGAGCTGCACCCGGACAGCACC CTCAGCATGTGGCCGGATAACCGTATCGCCCGTGACGCGCACTATCTTTACCGGTATGACCGTCACGGC AGGCTGACAGAGAAAACCGACCTCATCCCGGAAGGGGTTATCCGCACGGATGATGAGCGGACTCACCGG TACCATTACGACAGTCAGCACCGGCTGGTGCACTACACGCGGACACAATATGAAGAGCCGCTGGTCGAA AGCCGCTATCTTTACGACCCGCTGGGCCGCAGGGTGGCAAAACGGGTGTGGCGACGTGAACGGGACCTG ACGGGCTGGATGTCGCTGTCACGGAAACCGCAAGTGACCTGGTACGGCTGGGACGGCGACCGGCTGACC ACAATACAGAACGACAGAACCCGCATCCAGACGATTTATCAGCCGGGGAGCTTCACGCCACTCATCAGG GTTGAAACCGCCACCGGTGAGCTGGCGAAAACGCAGCGCCGCAGCCTGGCGGATGCGCTTCAGCAGTCC GGCGGCGAAGACGGTGGCAGTGTGGTGTTCCCGCCGGTGCTGGTGCAGATGCTCGACCGGCTGGAAAGT GAAATCCTGGCTGACCGGGTGAGTGAGGAAAGCCGCCGCTGGCTGGCATCGTGCGGCCTGACTGTGGCG CAGATGCAAAGCCAGATGGACCCGGTATACACGCGGGCGCGAAAAATCCACCTGTACCACTGCGACCAT CGCGGCCTGCCGCTGGCCCTTATCAGTAAGGAAGGGGCAACAGAATGGTGCGCAGAATACGATGAGTGG GGCAACCTGCTGAATGAAGAGAACCCGCATCAGCTGCAGCAGCTTATCCGCCTGCCGGGGCAGCAGTAT GATGAGGAGTCCGGCCTGTATTACAACCGCCACCGCTATTATGACCCGCTGCAGGGGAGGTATATCACT CAGGATCCGATTGGACTGAAGGGGGGATGGAATTTTTATCAGTATCCGTTGAATCCGGTTCAGTATATA GATTCAATGGGACTGGCATCAAAATATGGACACTTAAATAATGGCGGATATGGAGCGAGACCGAACAAA CCGCCTACGCCCGATCCAAGTAAATTTCCAGACATAGCGAAACAATTAAGACTGCCATATCCTATTGAC CAGGCCAGTAGTGCGCCTAATGTTTTCAAAACATTCTTCAGAGCATTAAGCCCTTACGACTACACACTG TATTGCAGGAAGTGGGTAAAACCAAATCTGACTTGTACGCCACAGGATGATCCCCAGTATCCAGGGATG GATACAAAGACAGCAAGTGATTACCTGCCACAGACAAATTGGCCAACAACTCAATTACCAGCAGGATAT ACTTGTGCAGAACCCTATTTATTCCCTGACATTAATAAACCCGATGGGCCAGCAACAGCAGGGATAGAT GATTTGGGTGAAATTTTAGCTAAAATGAAACAGAGAACATCGAGAGGAATAAGAAAATGA [SEQ ID NO: 19] MC018 MSGKPAARQGDMTQYGGSIVQGSAGVRIGAPTGVACSVCPGGVTSGHPVNPLLGAKVLPGETDIALPGP 1399 prot LPFILSRTYSSYRTKTPAPVGSLGPGWKMPADIRLQLRDNTLILSDNGGRSLYFEHLFPGEDGYSRSES LWLVRGGVAKLDEGHRLAALWQALPEELRLSPHRYLATNSPQGPWWLLGWCERVPEADEVLPAPLPPYR VLTGLVDRFGRTQTFHREAAGEFSGEITGVTDGAGRHFRLVLTTQAQRAEEARQQAISGGTEPSAFPDT LPGYTEYGRDNGIRLSAVWLTHDPEYPENLPAAPLVRYGWTPRGELAVVYDRSGKQVRSFTYDDKYRGR MVAHRHTGRPEIRYRYDSDGRVTEQLNPAGLSYTYQYEKDRITITDSLNRREVLHTQGEGGLKRVVKKE HADGSVTQSQFDAVGRLRAQTDAAGRTTEYSPDVVTGLITRITTPDGRASAFYYNHHSQLTSATGPDGL EIRREYDEWGRLIQETAPDGDITRYRYDNPHSDLPCATEDATGSRKTMTWSRYGQLLSFTDCSGYVTRY DHDRFGQMTAVHREEGLSQYRAYDSRGQLIAVKDTQGHETRYEYNAAGDLTTVIAPDGSRNGTQYDAWG KAICTTQGGLTRSMEYDAAGRVIRLTSENGSHTTFRYDVLDRLIQETGFDGRTQRYHHDLTGKLIRSED EGLVTHWHYDEADRLTHRTVKGETAERWQYDERGWLTDISHISEGHRVTVHYGYDEKGRLTGERQTVHH PQTEALLWQHETRHAYNAQGLANRCIPDSLPAVEWLTYGSGWLAGMKLGDTPLVDFTRDRLHRKTLRRF GRYELTTAYTPAGQLQSQHLNSLQYDRDYTWNDNGELIRISSPRQTRSYSYSDSGRLTGVHTTAANLDI RIPYATDPAGNRLPDPELHPDSTLSMWPDNRIARDAHYLYRYDRHGRLTEKTDLIPEGVIRTDDERTHR YHYDSQHRLVHYTRTQYEEPLVESRYLYDPLGRRVAKRVWRRERDLTGWMSLSRKPQVTWYGWDGDRLT TIQNDRTRIQTIYQPGSFTPLIRVETATGELAKTQRRSLADALQQSGGEDGGSVVFPPVLVQMLDRLES EILADRVSEESRRWLASCGLTVAQMQSQMDPVYTPARKIHLYHCDHRGLPLALISKEGATEWCAEYDEW GNLLNEENPHQLQQLIRLPGQQYDEESGLYYNRHRYYDPLQGRYITQDPIGLKGGWNFYQYPLNPVQYI DSMGLASKYGHLNNGGYGARPNKPPTPDPSKFPDIAKQLRLPYPIDQASSAPNVFKTFFRALSPYDYTL YCRKWVKPNLTCTPQDDPQYPGMDTKTASDYLPQTNWPTTQLPPGYTCAEPYLFPDINKPDGPATAGID DLGEILAKMKQRTSRGIRK [SEQ ID NO: 43] MC019 ATGGCTGCGGCAGCACAAGGTGTGGTAAACGCCGCAACCCAACAACCAGTTCCTGCACAAATTGCCATT 7863 GCAAATGCCAATACGGTGCCCTACACCCTTGGAGCGCTGGAATCGGCCCAAAGCGTTGCCGAACGTTTC GGTATTTCGGTGGCTGAGTTACGCAAACTCAACCAGTTTCGTACGTTTGCTCGAGGTTTTGATAATGTC CGCCAGGGTGATGAACTGGATGTCCCGGCACAAGTTAGTGAAAATAATTTAACCCCGCCACCGGGTAAT AGCAGTGGCAACCTTGAGCAACAGATAGCCAGTAGTTCACAGCAAATCGGGTCTCTGCTCGCCGAGGAT ATGAACAGCGAGCAAGCGGCAAATATGGCGCGTGGATGGGCCTCTTCTCAGGCTTCAGGCGCAATGACA GACTGGTTAAGCCGCTTCGGTACCGCAAGAATCACGCTGGGCGTGGATGAAGATTTTAGCCTGAAGAAC TCCCAGTTCGATTTTCTCCATCCGTGGTATGAAACGCCTGATAATCTCTTTTTCAGTCAGCATACTCTC CATCGTACTGACGAGCGTACGCAGATTAACAACGGCTTGGGTTGGCGTCATTTCACTCGCACATGGATG TCGGGGATCAACTTCTTTTTCGAGCACGATCTTAGCCGTTACCACTCCCGCGCCGGCATTGGGGCGGAG TACTGGCGCGACTATCTAAAATTAAGCAGTAACGGCTATTTGCGACTGACCAACTGGCGCAGCGCACCT GAACTGGACAACGATTATGAAGCACGCCGGGCCAATGGCTGGGATGTACGCGCAGAAGGCTGGCTACCC GCCTGGCCGCACCTTGGCGGTAAACTGGTCTATGAACAGTATTATGGCGATGAAGTGGCCCTGTTCGAT AAAGATGATCGGCAAAGTAATCCTCATGCCATAACCGCTGGACTTAACTATACCCCCTTCCCGCTGATG ACCTTCAGCGCGGAGCAACGCGAGGGTAAACAGGGCGAAAATGACACCCGTTTTGCCGTCGATTTTACG TGGCAACCTGGAAGCGCGATGCAGAAACAGCTTGACCCGAATGAAGTCGATGCACGGCGTAGCCTTGCA GGCAGCCGTTTTGATCTGGTGGATCGCAACAACAACATCGTTCTGGAATATCGCAAAAAAGAACTGGTT CGCCTGACCCTGACAGACCCCGTGACAGGGAAGTCAGGAGAAGTGAAATCACTGGTTTCGTCGCTACAA ACCAAATATGCCCTGAAAGGCTATAACGTCGAAGCCACCGCTCTGGAAGCTGCCGGTGGTAAAGTGGTT ACAACGGGTAAAGATATTCTGGTTACCCTGCCGGCGTACCGGTTCACCAGTACGCCAGAAACCGATAAC ACCTGGCCGATTGAAGTCACCGCTGAAGATGTCAAAGGCAATTTTTCGAATCGTGAACAGAGCATGGTA GTCGTTCAGGCTCCTACGCTAAGCCAGAAAGATTCCTCGGTATCGTTAAGTAGCCAGACGTTGAGCGCG GATTCCCATTCAACCGCCACACTGACTTTTATTGCGCATGATGCAGCAGGTAATCCTGTTATCGGGCTG GTGCTCTCGACGCGTCACGAAGGTGTTCAGGACATCACCCTTTCTGACTGGAAAGATAATGGTGACGGA AGCTATACCCAGATCCTGACCACAGGAGCGATGTCTGGCACGCTGACGCTGATGCCACAGCTGAACGGT GTGGATGCGGCTAAAGCCCCCGCCGTGGTGAATATCATTTCTGTTTCGTCATCCCGGACTCACTCGTCA ATTAAGATTGATAAGGACCGTTATCTCTCCGGGAATCCTATCGAGGTGACGGTAGAACTGAGAGATGAA AATGACAAACCTGTTAAGGAGCAAAAACAGCAACTGAATACCGCAGTCAGCATCGACAACGTGAAACCT GGTGTCACTACAGACTGGAAAGAAACCGCAGATGGCGTCTATAAGGCAACCTATACCGCCTATACCAAA GGCAGTGGGCTTACTGCGAAGCTGTTAATGCAAAACTGGAATGAAGATTTGCATACCGCTGGATTTATC ATCGACGCCAACCCGCAGTCAGCGAAAATTGCGACATTATCTGCCAGCAATAATGGTGTGCTCGCCAAT GAGAATGCAGCAAACACCGTCTCGGTCAATGTCGCTGATGAAGGAAGCAACCCAATCAATGATCATACC GTCACGTTTGCGGTATTAAGCGGATCGGCAACTTCCTTTAACAATCAAAACACCGCAAAAACGGATGTT AATGGTCTGGCGACTTTTGATCTGAAAAGTAGTAAGCAGGAAGACAACACGGTTGAAGTCACCCTTGAA AATGGCGTGAAACAAACGTTAATCGTCAGTTTTGTCGGCGACTCGAGTACCGCGCAGGTTGATCTGCAG AAGTCGAAAAATGAAGTGGTCGCTGACGGCAATGACAGTGCCACAATGACCGCGACAGTTCGGGATGCA AAAGGCAACCTGCTCAATGACGTCAAGGTCACCTTCAATGTCAATTCAGCAGCAGCGAAACTGAGCCAA ACCGAAGTGAATAGCCACGACGGGATCGCCACAGCTACGCTGACCAGTTTGAAAAATGGTGATTATACG GTTACGGCCTCTGTGAGCTCTGGTTCTCAGGCTAATCAACAGGTGATTTTTATCGGTGATCAAAGTACT GCTGCCCTGACCCTCAGTGTGCCTTCAGGTGATATCACCGTCACCAACACAGCTCCGCTACATATGACT GCAACCTTGCAGGATAAAAATGGCAATCCACTAAAAGATAAAGAAATCACCTTCTCTGTGCCAAACGAC GTCGCAAGTCGGTTCTCGATTAGCAACAGCGGAAAAGGCATGACGGATAGCAACGGGACTGCAATCGCC TCCCTGACCGGCACGTTAGCGGGCACGCATATGATCACGGCTCGTCTGGCTAACAGCAATGTCAGCGAT ACACAGCCAATGACGTTTGTGGCGGATAAAGACAGAGCGGTTGTCGTTCTGCAAACATCGAAAGCGGAA ATCATTGGGAATGGCGTGGATGAGACGACTCTGACAGCAACAGTTAAAGATCCTTTTGATAACGTGGTT AAAAATCTTTCAGTAGTCTTCCGCACCTCCCCCGCAGACACGCAACTGAGTCTGAACGCGCGTAATACT AATGAGAACGGTATTGCCGAAGTTACCCTTAAGGGCACGGTTTTGGGTGTTCATACAGCCGAAGCCATA CTGCTTAACGGCAACAGAGATACGAAAATCGTCAATATTGCGCCCGATGCCAGCAACGCGCAGGTCACC CTGAACATCCCTGCACAACAGGTGGTGACGAATAACAGTGACAGCGTGCAGCTGACGGCGACGGTGAAA GACCCGTCGAATCATCCGGTGGCGGGAATAACGGTGAACTTCACCATGCCACAGGACGTGGCGGCAAAC TTTACCCTTGAAAATAACGGTATTGCCATCACTCAGGCCAATGGCGAAGCGCATGTCACCCTCAAAGGC AAAAAAGCGGGCACGCATACTGTGACCGCCACGCTGGGTAACAATAATGCCAGCGATGCGCAACCAGTC ACCTTCGTGGCGGATAAGGACAGCGCGGTTGTCGTTCTGCAAACATCGAAAGCGGAAATCATTGGGAAT GGCGTGGATGAGACGACTCTGACGGCAACAGTGAAAGATCCTTTTGATAACGCAGTAAAAGATCTACAG GTCACCTTCAGTACCAACCCCGCAGATACTCAACTTAGTCAGAGCAAAAGCAATACTAACGACAGTGGT GTGGCCGAAGTTACCTTTAAGGGCACGGTTTTGGGTGTTCATACAGCCGAAGCCACACTGCCTAACGGC AACAACGATACGAAGATAGTCAATATTGCGCCCGATGCCAGCAACGCGCAGGTTACGCTGAACATCCCT GCTCAACAGGTGGTGACGAATAACAGCGACAGCGTGCAGCTGACGGCGACGGTGAAAGATCCGTCGAAT CATCCGGTGGCGGGAATAACGGTGAACTTCACCATGCCACAGGACGTGGCGGCAAACTTTACCCTCGAA AATAACGGTATTGCCATCACCCAGGCCAATGGGGAAGCGCATGTCACGCTCAAAGGTAAAAAAGCGGGT ACGCATACGGTTACCGCAACGCTGAGTAATAACAATACCAGTGATTCACAGCCGGTAACGTTTGTGGCG GACAAAACCTCGGCTCTGGTTGTTCTTCAGATATCAAAAAATGAGATCACAGGTAATGGCGTCGATAGC GCAACGCTAACTGCAAGGGTCAAAGATCAGTTCGACAATGAGGTGAACAATCTTCCGGTAACATTCAGC ACAGCTTCTTCAGGCCTCACCCTGACCCCAGGGGAAAGTAATACCAATGAGTCTGGCATCGCGCAGGCC ACTCTCGCAGGCGTTGGCTTTGGTGAGCAGACGGTCACTGCATCACTGGCTAATAATGGTGCCAGCGAC AACAAAACTGTGCATTTTATTGGCGACACAGCGGCGGCAAAAATTATCGAGTTGACGCCTGTCCCAGAC AGCATAATCGCAGGTACCCCGCAGAACAGCTCCGGCAGCGTCATCACCGCCACAGTCGTTGATAATAAT GGCTTTCCGGTGAAAGGTGTGACTGTGAACTTCACCAGCAACGCAGCGACAGCCGAAATGACGAATGGC GGTCAAGCCGTGACGAACGAACAGGGTAAGGCTACCGTCACTTATACCAATACCCGCTCCTCGATAGAA TCAGGAGCGAGACCGGATACCGTTGAGGCCAGTCTGGAAAATGGTAGCTCCACGCTTAGCACATCAATT AATGTCAACGCTGATGGGTCTACGGCACATCTCACCTTGCTACAGGCACTTTTTGATACAGTCTCCGCA GGCGACACTACCAATCrGTATATTGAGGTGAAGGATAATTACGGCAACGGAGTACCCCAGCAGGAGGTA ACCCTCAGCGTTTCACGAAGTGAAGGTGTGACCCCCAGTAATAACGCTATATATACGACCAATCACGAC GGCAATTTTTACGCAAGCTTTACCGCTACAAAAGCCGGGGTATACCAAGTGACGGCAACCCTCGAAAAT GGCGATTCGATGCAACAAACAGTGACCTATGTGCCGAACGTAGCGAATGCTGAAATCTCGCTGGCAGCC TCGAAGGATCCGGTAATTGCCAACAATAACGATCTCACGACACTAACAGCAACAGTCGCTGATACAGAG GGCAATGCGATAGCCAACAGTGAGGTAACATTTACTCTGCCGGAAGATGTGAGGGCGAACTTCACGCTG GGCGATGGCGGTAAAGTGGTTACTGATACTGAAGGCAAAGCGAAAGTCACGCTGAAAGGTACAAAAGCA GGCGCTCATACTGTTACAGCATCGATGGCTGGCGGTAAGAGTGAGCAGTTGGTGGTGAACTTTATTGCG GATACACTCACTGCGCAGGTTAATCTTAACGTTACCGAGGACAATTTTATCGCTAATAACGTCGGGATG ACCAGGCTGCAGGCAACAGTGACTGATGGAAACGGCAACCCGTTASCCAATGAGGCGGTGACATTCACG CTACCGGCAGATGTGAGCGCAAGCTTTACTCTCGGACAAGGCGGTTCCGCCATTACTGACATCAACGGC AAGGCTGAAGTTACACTGAGCGGTACAAAATCCGGCACCTACCCCoTGACAGTTAGCGTGAACAATTAT GGTGTCAGTGATACGAAACAGGTGACTTTGATTGCCGATGCTGGTACCGCAAAACTAGCCTCCTTAACC TCTGTATACTCATTCGTCGTCAGCACGACCGAGGGCGCGACCATGACTGCAAGCGTCACTGACGCTAAC GGCAACCCGGTAGAAGGTATAAAAGTTAATTTCCGCGGAACTTCCGTCACGCTAAGCAGCACCAGCGTT GAAACGGATGATCGGGGTTTCGCTGAAATTCTTGTGACAAGCACCGAGGTCGGACTGAAAACAGTTTCA GCCTCTCTGGCAGATAAACCTACTGAAGTCATCTCGCGATTACTGAATGCAAAAGCAGATATTAATTCT GCAACGATTACCAGTCTGGAGATACCTGAAGGTCAGGTCATGGTCGCACAAGACGTAGCAGTTAAAGCT CACGTCAACGACGAGTTTGGCAATCCGATTCTTAATGAATCTGTAACATTCAGTGCAGAACCACCAGAG CACATGACCATCAGCCAAAATATTGTCTCTACTGATACGCATGGTATAGCCGAGGTCACTATGACGCCC GAAAGAAACGGTTCGTATATGGTGAAAGCATCCCTGGCGAATGGATCCTCTTATGAGAAGGATCTGGTG GTAATCGATCAAAAACTGACACTCTCGGCGTCCAGCCCGCTTATCGGTGTCAATTCCCCAACAGGTGCA ACTCTGACGGCAACGCTAACTTCTGCAAATGGCACTCCAGTGGAGGGTCAGGTCATCAACTTTAGCGTA ACGCCAGAAGGTGCGACGTTAAGTGGCGGAAAAGTGAGAACCAACTCTTCAGGTCAGGCTCCAGTCGTT CTGACCAGCAATAAAGTCGGTACATATACGGTGACTGCATCGTTCCATAACGGCGTAACAATACAGACA CAGACAATCGTGAAAGrCACTGGCAACTCAAGCACCGCCCATGTTGCTAGCTTTATCGCTGATCCATCG ACTATAGCCGCCACCAACAGTGATTTAAGTACCTTAAAGGCAACGGTTGAGGATGGCAGTGGTAACCTG ATCGAAGGTCTCACTGrGTACTTCGCCTTAAAAAGCGGCTCTGCCACATTAACGTCATTAACAGCGGTG ACAGATCAAAACGGAATCGCGACAACAAGCGTGAGAGGAGCGATAACGGGGAGCGTCACGGTAAGCGCA GTCACGACCGCTGGTGGAATGCAAACAGTAGATATAACGCTGGTGGCAGGCCCGGCAGACGCCTCGCAG TCCGTCCTTAAGAACAATCGGTCATCATTGAAAGGAGACTTTACCGATAGTGCTGAGCTACATCTTGTT CTGCACGATATATCAGGCAATCCGATCAAAGTTTCTGAAGGGCTGGAATTTGTGCAGTCAGGTACCAAC GCGCCCTATGTGCAAGTTAGTGCAATTGACTACAGTAAAAATTTCTCAGGCGAGTACAAAGCCACTGTT ACAGGCGGCGGAGAGGGTATCGCAACGCTGATCCCTGTATTGAATGGTGTTCATCAAGCGGGTCTGAGT ACCACAATACAATTCACTCGCGCAGAAGACAAAATAATGAGCGGTACAGTGTTAGTCAATGGTGCTAAC CTACCGACAACTACATTCCCTTCGCAGGGGTTCACTGGGGCGTATTATCAGTTGAATAATGACAACTTT GCCCCAGGAAAAACGGCGGCTGATTATGAGTTTTCAAGCTCTGCCTCCTGGGTTGATGTTGATGCTACC GGTAAAGTGACATTTAAAAATGTCGGCAGCAAATGGGAGAGGATTACGGCGACGCCAAAAACAGGCGGC CCTAGCTATATATACGAAATCCGAGTGAAGAGTTGGTGGGTGAACGCCGGCGATGCTTTCATGATATAC AGCCTTGCTGAAAATTTTTGCAGTAGCAATGGCTACACACTTCCCCTTGGAGACCATTTAAACCATAGT CGTTCCCGAGGCATCGGGTCACTGTACAGTGAATGGGGAGATATGGGGCATTACACGACTGAAGCTGGT TTTCATTCAAATATGTATTGGTCATCGAGTCCCGCAAACTCAAACGAACAATACGTAGTTTCCCTGGCA ACAGGTGATCAAAGCGTATTTGAAAAGCTTGGGTTTGCTTATGCGACATGTTATAAAAACCTCTGA [SEQ ID NO: 20] MC019 MAAAAQGVVNAATQQPVPAQIAIANANTVPYTLGALESAQSVAERFGISVAELRKLNQFRTFARGFDNV 2620 prot RQGDELDVPAQVSENNLTPPPGNSSGNLEQQIASTSQQIGSLLAEDMNSEQAANMARGWASSQASGAMT DWLSRFGTARITLGVDEDFSLKNSQFDFLHPWYETPDNLFFSQHTLHRTDERTQINNGLGWRHFTPTWM SGINFFFDHDLSRYHSRAGIGAEYWRDYLKLSSNGYLRLTNWRSAPELDNDYEARPANGWDVRAEGWLP AWPHLGGKLVYEQYYGDEVALFDKDDRQSNPHAITAGLNYTPFPLMTFSAEQRQGKQGENDTRFAVDFT WQPGSAMQKQLDPNEVDARRSLAGSRFDLVDRNNNIVLEYRKKELVRLTLTDPVTGKSGEVKSLVSSLQ TKYALKGYNVEATALEAAGGKVVTTGKDILVTLPAYRFTSTPETDNTWPIEVTAEDVKGNFSNREQSMV VVQAPTLSQKDSSVSLSSQTLSASSHSTATLTFIAHDAAGNPVIGLVLSTRHEGVQDITLSDWKDNGDG SYTQILTTGAMSGTLTLMPQLNGVDAAKAPAVVNILSVSSSRTHSSIKIDKDRYLSGNPIEVTVELRDE NDKPVKEQKQQLNTAVSIDNVKPGVTTDWKETADGVYKATYTAYTKGSGLTAKLLMQNWNEDLHTAGFI IDANPQSAKIATLSASNNGVLANENAANTVSVNVADEGSNPINDHTVTGAVLSGSATSFNNQNTAKTDV NGLATFDLKSSKQEDNTVEVTLENGVKQTLIVSFVGDSSTAQVDLQKSKVEVVADGNDSATMTATVRDA KGNLLNDVKVTFNVNSAAAKLSQTEVNSHDGIATATLTSLKNGDYTVTASVSSGSQANQQVIFIGDQST AALTLSVPSGDITVTNTAPLHMTATLQDKNGNPLKDKEITFSVPNDVASRFSISNSGKGMTDSNGTAIA SLTGTLAGTHMITARLANSNVSDTQPMTFVADKDRAVVVLQTSKAEIIGNGVDETTLTATVKDPFDNVV KNLSVVFRTSPADTQLSLNARNTNENGIAEVTLKGTVLGVHTAEAILLNGNRDTKIVNIAPDASNAQVT LNIPAQQVVTNNSDSVQLTATVKDPSNHPVAGITVNFTMPQDVAANFTLENNGIAITQANGEAHVTLKG KKAGTHTVTATLGNNNASDAQPVTFVADKDSAVVVLQTSKAEIIGNGVDETTLTATVKDPFDNAVKDLQ VTFSTNPADTQLSQSKSNTNDSGVAEVTFKGTVLGVHTAEATLPNGNNDTKIVNIAPDASNAQVTLNIP AQQVVTNNSDSVQLTATVKDPSNHPVAGITVNFTMPQDVAANFTLENNGIAITQANGEAHVTLKGKKAG THTVTATLSNNNTSDSQPVTFVADKTSALVVLQISKNEITGNGVDSATLTATVKDQFDNEVNNLPVTFS TASSGLTLTPGESNTNESGIAQATLAGVAFGEQTVTASLANNGASDNKTVHFIGDTAAAKIIELTPVPD SIIAGTPQNSSGSVITATVVDNNGFPVKGVTVNFTSNAATAEMTNGGQAVTNEQGKATVTYTNTRSSIE SGARPDTVEASLENGSSTLSTSINVNADASTAHLTLLQALFDTVSAGDTTNLYIEVKDNYGNGVPQQEV TLSVSPSEGVTPSNNAIYTTNHDGNFYASFTATKAGVYQVTATLENGDSMQQTVTYVPNVANAEISLAA SKDPVIANNNDLTTLTATVADTEGNAIANSEVTFTLPEDVRANFTLGDGGKVVTDTEGKAKVTLKGTKA GAHTVTASMAGGKSEQLVVNFIADTLTAQVNLNVTEDNFIANNVGMTRLQATVTDGNGNPLANEAVTFT LPADVSASFTLGQGGSAITDINGKAEVTLSGTKSGTYPVTVSVNNYGVSDTKQVTLIADAGTAKLASLT SVYSFVVSTTEGATMTASVTDANGNPVEGIKVNFRGTSVTLSSTSVETDDRGFAEILVTSTEVGLKTVS ASLADKPTEVISRLLNAKADINSATITSLEIPEGQVMVAQDVAVKAHVNDQFGNPILNESVTFSAEPPE HMTISQNIVSTDTHGIAEVTMTPERNGSYMVKASLANGSSYEKDLVVIDQKLTLSASSPLIGVNSPTGA TLTATLTSANGTPVEGQVINFSVTPEGATLSGGKVRTNSSGQAPVVLTSNKVGTYTVTASFHNGVTIQT QTIVKVTGNSSTAHVASFIADPSTIAATNSDLSTLKATVEDGSGNLIEGLTVYFALKSGSATLTSLTAV TDQNGIATTSVRGAITGSVTVSAVTTAGGMQTVDITLVAGPADASQSVLKNNRSSLKGDFTDSAELHLV LHDISGNPIKVSEGLEFVQSGTNAPYVQVSAIDYSKNFSGEYKATVTGGGEGIATLIPVLNGVHQAGLS TTIQFTRAEDKIMSGTVLVNGANLPTTTFPSQGFTGAYYQLNNDNFAPGKTAADYEFSSSASWVDVDAT GKVTFKNVGSKWERITATPKTGGPSYIYEIRVKSWWVNAGDAFMIYSLAENFCSSNGYTLPLGDHLNHS RSRGIGSLYSEWGDMGHYTTEAGFHSNMYWSSSPANSNEQYVVSLATGDQSVFEKLGFAYATCYKNL [SEQ ID NO: 44] MC021 GTGCCTTACACGCTTGGTGCGCTGGAATCAGCGCAAAGCGTTGCTAATCGCTTCGGTATTTCACTGGAG 5037 GAGCTTCGTCGTCTTAATCAGTTCCGTACTTTTGCTCGCGGCTTTGATAACGTGCGCCAGGGTGAAGAA CTGGATGTTCCGGCAACAACCTCGCAGAAAAGCCATGAGCAACAAAATGCCGTACCGCCTGCGAATGGC GAAAACACGCTGGAGAATCAAATAGCCAGCACCTCGCAGCGAGTTGGCACTCTGCTTTCACAAGATATG AATAGTGAGCAGGCCAGCGGCATGGCGCGTGGTTGGGCGTCTTCAGAAGCCTCAGGCGCGATGACTGAT TGGTTAAATAACTTTGGTACTGCGAGAATCTCTCTGGGTGTGGATGAAGATTTTAGCCTGAAAAATTCG CAATTCGACTTCCTGCATCCGTGGTATGACACACCTGATTATCTGCTCTTCAGCCAGCATACCCTTCAC CGAACAGACGATCGTACCCAGATGAACACCGGTTTGGGCTGGCGTCATTTCACCTCCAGCTGGATGTCA GGCATCAACCTTTTTTTTGACCACGACCTGAGCCGCTATCACTCCCGCGCAGGGCTTGGCGCAGAATAC TGGCGTGATTATCTGAAGTTGAGCAGCAACGCTTATATCGGCCTGACCGGCTGGCGTAGCGCACCAGAA TTGGATAACGACTTCGAAGCCCGCCCGGCCAACGGCTGGGATTTACGCGCGGAAGGCTGGTTACCTGCC TGGCCACAACTGGGGGGAAAACTGGTCTATGAACAATACTATGGCGATGAAGTGGCGCTGTTTGACAAG AATGATCGTCAAAGTAACCCCCATGCTATTACGGCAGGCCTCAACTATACCCCCTTCCCGCTTCTGACT CTCAGTGCGGAACAGCGTCAGGGGAAGCAAGGTGAAAATGACACACGTTTTGCCGTTGATCTGACCTGG CAACCCAGCAGTTCAATGCAGAAACAGCTTAATCCGGACGAAGTGGCCGGACGGCGCAGTCTGGCCGGT AGTCGTTATGACCTGATTGATCGCAACAACAACATCGTTCTGGAATACCGCAAGAAAGAGCTGATTCGC CTGAGTCTGCTGGATCCGGTGAAAGGGAAGTCTGGAGAAATAAAACCGCTGGTTTCCTCGCTACAGACC AAATATGCCCTTAAAGGCTATAACATCGAAGCCGCTGCGCTGGAAGCTGCCGGAGGTAAAGTCAGCACG TCTGGAAAAGATATCACGGTCACGCTGCCAGGTTACCGCTTCACTAACACCCCAGAAACCGATAATACA TGGTCGATAGACGTTACCGCCGAGGATGTAAAAGGTAACCTGTCACGGCATGAACAAAGCATGGTAGTT ATTCAGGCTCCGACATTAAGCCAGAAAGATTCTCTGTTATCCGTCAATCCGCTAACCGTGGCTGCAGAT AAAAAATCGACGACCACATTGACCGTTACTGCGCACGATTCCGACGGAACTCCGGTGCCGGGGCTGGCG CTGCAAACCCGCAGTGAAGGCGTTCAGGATATCACCCTGTCTGACTGGACAGATAACGGTGATGGTAGT TACACACAGATACTGACCGCCGGAACGACATCAGGTTCAGTAACACTGACGCCGCAAATTAACGGTGAG AGTGCGGTAAAAGAATCCATCGTCGTTAATATCGTCCCTGTTGTCTCATCCCGCGACCATTCATCAATA ACAATTGATAACGTATCGTATTATGCCGGAGACGACATCAAGGTTAGGGTGGAACTGAAAGACGATAGC AATCAACCGGTTGCATATCAAAAAGAGGAATTGGTAAAAGCCGTTACTGTCGAAAACAGCAAACCTGGC GCCACGATTGTCTGGCACGAAGAGCAGCCGGGGGTTTATGCCGCGAATTATCCGGCCTATAAGCAAGGG ACTGCACTAAGGGCACAACTTAGCCTTCACAACTGGAATGCTCCACTGCAATCGCATATTTATAACATT GAGGCAAACCAGAATAAGGCTCGCGTTGCCACATTATCAGCGACAAATAATGACGTTTACGCCGATAAA AAGACATTTAATACCCTCACGATCAACGTCACTGATGAGAGTGATAATCCCCTGACAAATCATCAGGTC ACCTTTAAGAATGAAAAAGGAAGCGCGGAGTTTGTCGAACCGCCGCAGCAAAATACGGATGCATATGGT GTTGCCACAATAAACATGGTAAGTCAGGTTGCGGAAGAAAATACGATTAGCGCCACGCTGCCAAATGGT TTTTCACAACGGATAATTGCGAAATTCGTTAGCGATTCGAGTACGCCAAAATTCAAACAACTGGTTGCC GATCCAGATACCATTATTGCTGGCAACAGCCAGGGCAGTACTCTGACCGCCATCATCACAGACTTTCAT AACAACCCGTTAAAAGATATGAAAGTGAATTTTGTGGCACCTGGTGGCTCGCAACTGGACAACACGACC GCCACAACAGACCAGTCCGGTATTGTGCGGGTGCACCTGACCAGTTCAAAAGCTGGTAGCTATTCCGTC GATGCCTCGCTTGAGGTGGATAAAAATATTCACCAGTCGGTCACGATCACCGTGGTCCCAAACAGGGAA CAATCGGTAATGACCTTGAATGCCGGGTCGGGCAGTGCGATCGCTAACAATACAAATATCGTTACCCTG ACTGCCAGTGTGAAAGATGTTTATGGACACCCGTTGCCGGATGAGGATGTGAAATTTACCTTGCCAGCC TCCATGACCGGGAACTTCACGCTAAGTAGTGAAACCGCCCGCACCGATGCAAACGGTGATGCCGTGGTC ACATTGCGAGGCACAAAAGCGGGTGAGTTTACAGTTACGGCGACGCTGACCAGAAATAATACCGTTGCT TATCAGCAAGTCACTTTTATTGGGGATACAAACAGTGCGCAGCTCCAGCCGCTGACTGCCTCATTAAAT TCCATTGTTGCGGGTAACAGTACGGGGAGTACCCTGACGGCAACGATCCTGGACGCTTACCAAAATCCG CTTAAAGACCAGTTGGTCACTTTCCAGAGTAACGATGTCACTCTAAGCGAAACAGAAGTCACCACCAAT ACGCTGGGTCAGGCGACGGTAACAATGACCAGCAATATTGCCGGACAACATAACGTCGTGGTGAGCCGG AAAGCGCAAGCTTCCGATAATAAAACGTTTAGTTTATCAGTGCTACCGGATGAAAGTTCGGCGAAGGTA ATAAGTATAACCGGAGCCGAAAAAACGATAACGGTGGGCGAAAACATCACGCTACGGATACTCGTCCAG GACGCGTTTAACAATGTAATCGCGGGTCAACGCGTCAGATTAAGTGCGCAGCCAACAACTAACATTACG ATAGGCGATACGGCTTACACCGATAATAACGGTTATGCGTACGTTAACCTTCTCAGCACCCAACCTGGG GTTTATCAGGTGACGGCAACGCTGGACAATAACAGTAGTAGTAAGGTTGACGTGAATGTGGCAAATGGC AAACTCGAGTTAACATCATCGAAACCAGAAACTACGGTCCATAATAGTGAGGGTATTACGGTGACCGCA ACGGCGAGAAATGCGCGGGGTGAATTGATGCCAGGGCAAATTATCACCTTTAGCGTAACGCCTGAAGGT GCAACGCTAAGCAATACAGGGGAAGTCCTTACTGACCAGTCAGGTCAGGCCAAAGTGACGCTGACCAGT GACAAAGTGAATGTCTATACCGTTACGGCCATAATGGGCAAAGATGTTCCCGTTCAGAGCCAGGTAACG GTTGCGGTTAAGGCAGATGCTAAAACGGCACATGTTGTGAGCGTCGTGGCTTCTCCTGACACCATCACC GCCGACGGCATCGATAGCAGCACCATCACTTGACGAGTAGAAGATGATTACGGATTCCCGGTTGAAGGT GTCGATATTAGTCATGGCTTAGACACCAAAGGCAGCCCGGTAGTTAATATTCCAACTACGCGTACCGAT CAGTCCGGGCAAGTCACGGCGACAATAACCAGTACATTGGCAGAAACCTTAACAGTCAATGTGCAAGTT CCTGGCACAGCCAACCAATCCGCAACCATTACATTGGTTGCCGGCACGGCCGATGAAAGTAAGTCAATT TTGAAATCCGATGTTGACACTCTGAAGGCTGACTACCAGCAGAGCGGAAAACTTACGCTAACATTGCAA GACAAGTACGGTAACCCGATAGTGACGTCTGATCATCTGGAATTTGTCCAGTCAGGCCCCTTCGTGAAC TTTCTCAAGTTGAGCGATATTGATTACAGCCAAAGAAATTATGGCGAGTACACCGTGACTGTCACTGGC GGAAAAGAGGGAACAGCGACACTCATTCCCATGCTGAACGGGGTTCATCAGGCAAACTTAAGCATATCG CTGAATCTCATCCAATCGATAAAAGAAATGTCCGGTCATGTCACTGCAAACAACCATACCTTCTCCACG GCTAAATTCCCGAGCGAAGGCTTTGCAGGAGCGTATTACACACTCAACAATGATAACTTTGAAGCGGGT AAAACCGTTGATGATTATATGTTTTCAAGTTCACAGGGTTGGGTGTCTGTCGATGCTTCGGGTAAAGTT TCTTTCGCAAATATCGGCGATCAAACGTCAGTCACAATAAGCGCTGTTCCCCGACAAGGAGGTACAACC TACCAGACCTTAATTAAGCTGAAAGGCTGGTGGGTGAATAATGGAAATCATACCAATATCTGGCTAGCT GCCAATGCGCTCTGTCATGCTAAAAATGATGGATATAATCTTCCTGGCATCACACATTTGACGTCTGGC GAAAACAAACGCACGCAGGGATCACTGTATGGTGAATGGGGGAACGTTGGAGCGTTTTCCAGTAATTCG GAATTTACACCGGGAGCTTACTGGACAAGTGAATCTGATGATTACAGTCGGCACTACTATGTGCAGATG CTAACCGGTATGACCGGAAGCGACGCTGATTCCAGCCCCCAACTGACCGCCTGCCGTAAATCACTTTAA [SEQ ID NO: 21] MC021 MPYTLGALESAQSVANRFGISLEELRRLNQFRTFARGFDNVRQGEELDVPATTSQKSHEQQNAVPPANG 1678 prot ENTLENQIASTSQRVGTLLSQDMNSEQASGMARGWASSEASGAMTDWLNNFGTARISLGVDEDFSLKNS QFDFLHPWYDTPDYLLFSQHTLHRTDDRTQINTGLGWRHFTSSWMSGINLFFDHDLSRYHSRAGLGAEY WRDYLKLSSNAYIGLTGWRSAPELDNDFEARPANGWDLRAEFWLPAWPQLGGKLVYEQYYGDEVALFDK NDRQSNPHAITAGLNYTPFPLLTLSAWQRQGKQGENDTRFAVDLTWQPSSSMQKQLNPDEVAGRRSLAG SRYDLIDRNNNIVLEYRKKELIRLSLLDPVKGKSGEIKPLVSSLQTKYALKGYNIEAAALEAAGGKVST SGKDITVTLPGYRFTNTPETDNTWSIDVTAEDVKGNLSRHEQSMVVIQAPTLSQKDSLLSVNPLTVAAD KKSTTTLTVTAHDSDGTPVPGLALQTRSEGVQDITLSDWTDNGDGSYTQILTAGTTSGSVTLTPQINGE SAVKESIVVNIVPVVSSRDHSSITIDNVSYYAGDDIKVRVELKDDSNQPVAYQKEELVKAVTVENSKPG ATIVWHEEQPGVYAANYPAYKQGTALRQALSLHNWNAPLQSHIYNIEANQNKARVATLSATNNDVYADK KTFNTLTINVTDESDNPLTNHQVTFKNEKGSAEFVEPPQQNTDAYGVATINMVSQVAEENTISATLPNG FSQRIIAKFVSDSSTPKFKQLVADPDTIIAGNSQGSTLTAIITDFHNNPLKDMKVNFVAPGGSQLDNTT ATTDQSGIVRVHLTSSKAGSYSVDASLEVDKNIHQSVTITVVPNREQSVMTLNAGSGSAIANNTNIVTL TASVKDVYGHPLPDEDVKFTLPASMTGNFTLSSETARTDANGDAVVTLRGTKAGEFTVTATLTRNNTVA YQQVTFIGDTNSAQLQPLTASLNSIVAGNSTGSTLTATILDAYQNPLKDQLVTFQSNDVTLSETEVTTN TLGQATVTMTSNIAGQHNVVVSRKAQASDNKTFSLSVLPDESSAKVISITGAEKTITVGENITLRILVQ DAFNNVIAGQRVRLSAQPTTNITIGDTAYTDNNGYAYVNLLSTQPGVYQVTATLDNNSSSKVDVNVANG KLELTSSKPETTVHNSEGITLTATARNARGELMPGQIITFSVTPEGATLSNTGEVLTDQSGQAKVTLTS DKVNVYTVTAIMGKDVPVQSQVTVAVKADAKTAHVVSVVASPDTITADGIDSSTITSRVEDDYGFPVEG VDISHGLDTKGSPVVNIPTTRTDQSGQVTATITSTLAETLTVNVQVPGTANQSATITLVAGTADESKSI LKSDVDTLKADYQQSAKLTLTLQDKYGNPIVTSDHLEFVQSGPFVNFLKLSDIDYSQRNYGEYTVTVTG GKEGTATLIPMLNGVHQANLSISLNLIQSIKEMSGHVTANNHTFSTAKFPSEGFAGAYYTLNNDNFEAG KTVDDYMFSSSQGWVSVDASGKVSFANIGDQTSVTISAVPRQGGTTYQTLIKLKGWWVNNGNHTNIWLA ANALCHAKNDGYNLPGITHLTSGENKRTQGSLYGEWGNVGAFSSNSQFTPGAYWTSESDDYSRHYYVQM LTGMTGSDADSSPQLTACRKSL [SEQ ID NO: 45] MC022 ATGGTCGCTAAATTAAAACCAGATGTTTTTGTTAATACTAATCCTTTTTTAGAAGCAATGTATAAGGAG 2409 AGGCTTAGTCATAAAGGCTATTCTGATAAAATTGCTTTAAGTATTAATGATAAGAAATATAATGTAAAC TCTAAGGATATTGAAAATATTCTTGATGGCAAAGGGGATTTATTTAAAAAACGTACACTGTGGGAGTTT GTTCGCGATCTTTTTCCTGGCTCTCATATTAAAGAAGTCAAAGGCTTAATTTACGAATTTGTCACGAAA GTTGATAATAAAGCCGAGGTGTTCGATAAGATTAAATCTCTGGCAAAAAAAGAACAACAATGGCGATTT AGTACTAAGACAGACTTTACCACAAATGAAAATAATGAAGTTATTGTGAGTAGATCCTTTAATCTCTAC ACGGGGGCTACTTCGAATGATAACGAAAAAAAACAGGTTTCTTCAGAGAGATTAACGCTTGATAATTAT CTCGATGATTTACATTTTGATAATTCTCCCTTGGTGAGATTAACGTTTGATAATTATTCTGTAAAACTT GCGACGCTGATTAAAAATAAAATTCCTATTATTAATACAACAATCAATTTATCATCGTTGTCTAAGGAT GTTTTAAATTCATTAAAATATTGTAGTTTTAAGAATGTAATTTTTTCAGGAGTGATAAACAGCCCTAAC CTTGAAGGTCCGGTTTTTGAAAATTGCTATTTCGATGATTGTAAATTCAACAACATACAGCTTTATGAG ACTAATGATGATACTGTGGAATCAGGAAATAAAAAACCAATAAAAGGTATGTTTAAAGGTTGTTTTATT TCTAAATGCAAAATTGAAAATTATAGATGTGAGACGTCTAAAATCTACACCGTTACACAACCTGATAGT ATTCAAGAAAAATTAGGTTCTTATCTCTTTATGCAGTCTTTCGTTCAGGATTGTATAATCCAGGGAGGA TGTTGTCCTGGCTCGAGTATACTTCTGAGTCATTTTTATAACTGTAATATAATAGGGCTTGATGCTCAT GGAATGGATTTTTTGGCAAATTCGTTCAACAAGTCTAATTATGATGAAATCAGGGGTCCGGATACGGGG ACTGTGTTTTATAATTGTAATTTGAAGCATATTAAAATAAACGATGGTCTTCGTGAAGATGGTTCAGAT AGAACTATGTTTAACCCCAAAGAGTATTTTTCTGATTACATTGAAAGAAGATCGAGAAATGTTAAGTTA GATGATAATTTTTCGAAATGCGTAGAGAGTATAAAGAAAGGGACCGATTCTTCATTTAGCAAGAAAAAT ACAGAGAACAATAATGTCTTCTTTAAAAATAGTAATTTGATTGGGGCAAATTTAGGCTATTATTACAGT GGAGATAGGTGCAAAGACTGTGCTATTGATCCAAATACAAATTATTCAAAAGATGGTCTTACAGCGCAA AAATACATGTATATGGATCTGGACGGAGCTATAAGTAAAGAACAAATACCTGATTTCTTAAAAAAGGTA AGTGCTATCAATATCGATGTAATAAATTTTTATAATTCCGAGTCAAAGACTAAGGAAAAATATAAAAAC GCATTTTTAGAGTTAGAGTCGTTTTTATCAACACTTTATGTTGAAAATAAATCGTACGAGGAAAAATAT CATTTTGATAATAGTAGGGTTGAGTTTTTTATTTTTAAAGATATGCAGGAAAATGCACAAAATATCATT AACAATATGATAGAAAGTGACCGGATTAAGTTTGTTGAATCTATAATAAATAAAATGATTCCGCCGCCA GATGGAACAATACTTACTGAAAATCCAAAAGAATATGTCCAAAAGCAAATAAAGGAGTCTCATAAAGAA TCTGCTACAAATGTAACATTTGATTATAAGGAACTTGCACCCATTTTTGAAGGTGTTGAAGAAAAACAA ATTAAAGCACTATCAAACCAACTGGAACATATAAAATCGTTTAAGACAGATTACGACTCAAGGCTCAAT AAGTATGCTCGCGATTTTTACTATTTTTCCAGTGCATTTGCAATTAACTGGGAGGATTTACTAAAAAAC TATCAGGAAATAAGAGCTTCCATTAAAGATTACGATGACTTATTGCGAGAAATTAAAGAGTTAATCATA AGTCGTAATAAATCATTAGAGGATAAAAGGACTTTATTTGATAACAAAAGGGACAATTGGAATAGTATA GAAGTGCAGGATGAAGTAAATGCATTGAATGCGAAAATTGTCGATTGTGATGATAAAATACGTTCTAAG CTTACTATTGTTCGAAATAATAGACTTGAGAATCAATATAAAGACGATAAAAACATCAGTGACGCGATG CGTAATATTCTGGATTGGTTCGAACGGTATCCCGATATTGTACAAAATATAACCCAGGCTTAA [SEQ ID NO: 22] MC022 MVAKLKPDVFVNTNPFLEAMYKERLSHKGYSDKIALSINDKKYNVNSKDIENILDGKGDLFKKRTLWEF  802 prot VRDLFPGSHIKEVKGLIYEFVTKVDNKAEVFDKIKSLAKKEQQWRFSTKTDFTTNENNEVIVSRSFNLY TGATSNDNEKKQVSSERLTLDNYLDDLHFDNSPLVRLTFDNYSVKLATLIKNKIPIINTTINLSSLSKD VLNSLKYCSFKNVIFSGVINSPNLEGPVFENCYFDDCKFNNIQLYETNDDTVESGNKKPIKGMFKGCFI SKCKIENYRCETSKIYTVTQPDSIQEKLGSYLFMQSFVQDCIIQGGCCPGSSILLSHFYNCNIIGLDAH GMDFLANSFNKSNYDEIRGPDTGTVFYNCNLKHIKINDGLREDGSDRTMFNPKEYFSDYIERRSRNLKL DDNFSKCVESIKKGTDSSFSKKNTENNNVFFKNSNLIGANLGYYYSGDRCKDCAIDPNTNYSKDGLTAQ KYMYMDLDGAISKEQIPDFLKKVSAINIDVINFYNSESKTKEKYKNAFLELESFLSTLYVENKSYEEKY HFDNSRVEFFIFKDMQENAQNIINNMIESDRIKFVESIINKMIPPPDGTILTENPKEYVQKQIKESHKE SATNVTFDYKELAPIFEGVEEKQIKALSNQLEHIKSFKTDYDSRLNKYARDFYYFSSAFAINWEDLLKN YQEIRASIKDYDDLLREIKELIISRNKSLEDKRTLFDNKRDNWNSIEVQDEVNALNAKIVDCDDKIRSK LTIVRNNRLENQYKDDKNISDAMRNILDWFERYPDIVQNITQA [SEQ ID NO: 46] MC023 ATGTTAAGGACGACACGATGGGTCGCTGCTATTATTTTTTTGTATTCTTTTCCGGGTTATGCTGAAGAA 2451 ACTTTTGATACGCACTTTATGATCGGCGGCATGAAAGGAGAAAAAGTTTCCGAATATCATTTCGATAAT AAACAACCGCTTCCAGGAAACTACGAACTTGATTTTTATGTAAATAACCAGTGGCGTGGAAAACAAGAT ATCACGATCCCAGAGTCACCAGTCAAACCATGTCTGCCTAAGGTGCTACTAACCAAACTGGGGGTAAAG ACCGGTAACCTCAATACAGAAGATAATTGTATTTTACTGGATAAAGCGGTTGATGGTGGACAATATCAG TGGGATATCAGTGAACACCGACTAAATTTAACAGTACCACAGGCGTATATCAATGAACTTGAAAGAGGT TACGTTCCCCCGGAAAGTTGGGATCGCGGCATTGATGCTTTTTATACCTCCTATAATTTAAGTCAGTAT CGCTCTTATGACAGCAATAATAACAGTAATACAGCCAGTTATGGCCGATTTAACAGTGGATTAAATTTA TTTAGTTGGCAGTTACACTCTGATGCCAGCTATAGCAAACCCGATGATATGAAAGGCACATGGCAAAGT AATACTCTTTACCTGGAACATGGCTGGTCGCAGATATTAAGCACAGTTCAGATAGGAGAAAATTACACA TCCTCACTCATATTCGACTCTCTGAGATTTAGCGGAATACGCTTATTTCGCGATATGCAAATGCTACCT GATTCTATGCAGAGCTTTACACCTTTAGTACAAGGTGTTGCGCAAAGTAATGCCTTGATAACGGTTTCG CAAAATGGCTACATCATTTACCAAAAAGAGGTTCCCCCGGGACCATTTACTATCGCAGATTTGCAACTC TCGGGCAGCGGCTCTGATCTCGATGTCAGCATAAAGGAAGCAGATGGCAGTGTTCGTTCCTTTTTGGTG CCCTACTCTTCCGTGCCTAACATGCTGCAACCTGGTATTTCAAATTTCGATTTTATCGCCGGACGCAGT AAGATATATGGTGTAAAGAATCAGGAGGACTTTCTCGAGGCAAATTATATATATGGCCTCAACAATCTT TTGACACTTTATGGCGGTACGATTTTATCCGATAACTATAATGCTATAACTCTGGGAAATGGTTGGAAT ACACCGCTGGGTGCCATCTCTTTTGACGCTACACGATCGAGTAGTAAGTTAAATAATGATATAACACAC GAAGGTACGAGCTATCAGGTCGCCTATAATAAATATCTAGTACAAACGGCCACTCGATTTAGCGTGGCC GCCTGGCGTTATGCTTCGCAGGATTACAGGACATTCAGCGACCATCTTTACGAAAATGATAAAATAAAT CATCAGAGTGACTATGACGATTTTTATGATATTGGCAGAAAAAATAGCCTTTCTGCCAATATCATGCAA CCTTTATCCAATAATCTGGGAAATGTATCATTAAGTGCGCTTTGGCGGAATTACTGGGGGCGAAGTGGA AATGCTAAAGATTACCAATTCAGTTATTCCAATAGCTGGCAACGCATCAGTTATACTTTCTCTGCCAGC CAATCCTATGATGAAAACGACAAAGAAGAGGAGCGTTTTAATCTGTTTATCTCCATTCCTTTCTACTGG GGGGATGATATTGCCAAAACACGTCACCAAATTAACTTATCGAATTCGACCTCATTTTCCAAAGATGGC TATTCCTCCAACAATACTGGAATTACTGGCATAGCCGGTGAACATGATCAGTTAAATTATGGTATATAT GTTAATCAGCAACAACAAAATAATGATACATCGCTTGGTACGAATTTAAGCTGGAGAACTCCCATCGCC ACAATAGATGGCAGCTATAGCCATTCTAAAAACGCCTGGCAAAGTGGTGGAAGTATTAGTAGTGGATTA GTTGTCTGGCCCGGTGGTATTAATATCACTAACCAGCTATCCGATACATTTGCAATTCTGGATGCGCCT GGGTTAGAAGGCGCGCATATTAATGGACAAAAATACAACCGAACAAACAGCAAAGGCCAGGTTGTTTAC GACCTGATGATACCTCATCGTGAAAACCATCTGGTACTTGATACAGCAAACAGTGAAAGTGAAACAGAA TTGCAGGGCAATCGTCAAATTATTGCGCCTTACCGTGGAGCAGTTTCTTATGTGCAGTTTACAACTGAC CAACGTAAGCCCTGGTATATACAGGCACTGCGTCCCGATGGTTCGCCATTAACTTTTGGCTATGACGTA CTGGATCTCCAGGAAAACAATATTGGAGTCGTTGGCCAGGGTAGTCGCCTTTTTATTCGCGTAGATGAA ATTCCAACTGGCATAAAAGTTGCTCTCAATGATGAACAGAATTTATTCTGTACTATTACTTTTCAACAC GTTATCGATGAAAACAAAACATATATATGCCAGTAA [SEQ ID NO: 23] MC023 MLRTTRWVAAIFFLYSFPGYAEETFDTHFMIGGMKGEKVSEYHFDNKQPLPGNYELDFYVNNQWRGKQD  816 prot ITIPESPVKPCLPKVLLTKLGVKTGNLNTEDNCILLDKAVHGGQYQWDISEHRLNLTVPQAYINELERG YVPPESWDRGIDAFYTSYNLSQYRSYDSNNNSNTASYGRFNSGLNLFSWQLHSDASYSKPDDMKGTWQS NTLYLEHGWSQILSTVQIGENYTSSLIFDSLRFSGIRLFRDMQMLPDSMQSFTPLVQGVAQSNALITVS QNGYIIYQKEVPPGPFTIADLQLSGSGSDLDVSIKEADGSVRSFLVPYSSVPNMLQPGISNFDFIAGRS KIYGVKNQEDFLEANYIYGLNNLLTLYGGTILSDNYNAITLGNGWNTPLGAISFDATRSSSKLNNDITH EGTSYQVAYNKYLVQTATRFSVAAWRYASQDYRTFSDHLYENDKINHQSDYDDFYDIGRKNSLSANIMQ PLSNNLGNVSLSALWRNYWGRSGNAKDYQFSYSNSWQRISYTFSASQSYDENDKEEERFNLFISIPFYW GDDIAKTRHQINLSNSTSFSKDGYSSNNTGITGIAGEHDQLNYGIYVNQQQQNNDTSLGTNLSWRTPIA TIDGSYSHSKNAWQSGGSISSGLVVWPGGINITNQLSDTFAILDAPGLEGAHINGQKYNRTNSKGQVVY DLMIPHRENHLVLDTANSESETELQGNRQIIAPYRGAVSYVQFTTDQRKPWYIQALRPDGSPLTFGYDV LDLQENNIGVVGQGSRLFIRVDEIPTGIKVALNDEQNLFCTITFQHVIDENKTYICQ [SEQ ID NO: 47] MC024 ATGACGGCAGATGAGCGCAACGTGGTTAAAGCGGCAACCGACGATAGTATGGAAGCTGCTTATATGCTA 2166 AAAGATAATATCCGCTGGTATTATCATAATGGTGACCTATCATTACCCGCTAACTTCAGCAATAAAAAT AAACTGGTGGTGAACGGTAATTTAACGATTTCCGGCGATTATGATGATTATCTGTCAGGTAATGGTCAT CTGATTGTATTAGGTAATGTTATTGTCGATAACTTTATTAATCATGATTTCGCGTATGTCAAAGGACAG ATGACAGCGAAAGGTTTAGTTTATGCTGATTACAATGATCATAACTTTGAAGTGATGAAGGGAATTAGT GCGCGAGGCATTATTGTTTCCGATAAAGCAACGCAATTTGAAGTCATTAAAGCTGAATTTTATATCAAT GAAGATGGAAGTGGTGAAGGATATAACTGGGATGAGAATATTCAAAAAGCCTATTCACTGGTGACTGCC GATCTTTATGATCACACTGAAATCGAAACCGATAACATTTCCAATGCGTATCCTGACTATGATAGCGTC GCAGACAACATCGTTCAGGGTTTACCGCTTTTTCGAGATAAAGCCGCTCCTGAAATTAATGAGAAATTA AAATGGATTGAAACGGGGAAACTCGATAATTTCCCAGCGAATAAAATAAAGCATCAAGATCCACTGGTG GCACGTTTTCTGACTCATACAGAGAGTTTATCACCCGCCGTTATGCTGCAACTGTTACAGCACCCCGAT GACCAGACGCGTGAATCGATGGCGCAGTCCTGGCCCGCTCAACAGATGCATTGGCTTACCGATGAATTA ATTAAAGATGAGGCTGTTGCCAGAGGGCTGGTTAAAAACAGTAATATTTCCGCCGATGTGAATAAAAAA TTAATGTCTGTACCCGTCGAGAGCGTACAGCTGGAGCAGGCCAGACAGGATAATCTTTCTCCAGATATT GTTGCGTCGTTAAGTCATAGCCCCTTTCTCAGTGTACGCAAGACATTACTCAGCCATTACGATTACGCC TGGCTGGTTCCGACTGCAGTGGCCGATGAGTTGATAAATAACGAAGACCCGGAGTTACGTGAAAGAATT ACCGGAGCAGATTTAACCGCACAACAAGCAGTGATGTTGAGTAAAGATAAATCACTGAAAGTTCGTGAA GCATTAGCCCGGACGCTTACTGAATTAAAAATTACCCAACTGTCAGCAACCCTGCGTACAGAGGATATT GAACGTATCGCAGAACAAATGTATCTGGATAATAAAGAAAATAAAAATATCGTAAAGGTGTTATTGATA GCGTTGCCGGAGATGCGTCAACTGTCTCTGGCAAAAGAAGATGTGCACAATTTGCGCGAAGGTGCGCGT TATCTGACATCGAAGGACGTGATTAGTTATCTATTGACTCAGCATGATGTTCCCACCGTCTGGGATGAG CTGGCACGCGATAAATTATTGCCGCTGGAATATAAGAAACAGTTATGGCAACGCACATTAAATTTAATG ATGAGCAAACGGCAAGAAGATCAAGAGCAAGCCTACGAAGTACAGCTGGCGCTGATTGATAATGGTGTT GTTGACGAAGAGATGTTAAATAATGCCATTGATTTACTGGTTGATTTACCCGCTGAATACCGCTATCGA ATGCGTAACCAATTATTTGATAATAAAGAATTACCTTCCGGAATTATCAACAAACTCGATCAACAGTAT CGCTTCAACTCTGACTGGGCGCTGGCTGTTGTCAGTATGAAAAATAGCACCCGTAGACAAAGTGAAAGA GGATTACACCGCTGGAACCATGAGGATAGCGATATTTTTGCGGAACTGGCGACGATAAAAGATAAATCA GATGATGAATGGTGGCGTGCATTGCTGGAAAGTCGCAATGATCATTTGCGCCAAACGGCATTACGCAAC GCACATACCCCGGCGTCGTTGTTAACGACATTGACTGAGTCTCAGGATCGGTCGCTGGCTATTAATAAT CCACAGCTGGCTGCCGATGTGAAAACGGTGTGGCTAAAAGAGGATCCATCATTACTTTTATTTGTCGAT AAACCCGATCTTTCGCAGTTACGGGATTTAGTGAAAACCGGGGCAACGCGGAAAATTCGCAATGAAGCG CGTCACCGGCTTGAGGAAAAACAATGA [SEQ ID NO: 24] MC024 MTADERNVVKAATDDSMEAAYMLKDNIRWYYHNGDLSLPANFSNKNKLVVNGNLTISGDYDDYLSGNGH  721 prot LIVLGNVIVDNFINHDFAYVKGQMTAKGLVYADYNDHNFEVMKGISARGIIVSDKATQFEVIKAEFYIN EDGSGEGYNWDENIQKAYSLVTADLYDHTEIETDNISNAYPDYDSVADNIVQGLPLFRDKAAPEINEKL KWIETGKLDNFPANKIKHQDPLVARFLTHTESLSPAVMLQLLQHPDDQTRESMAQSWPAQQMHWLTDEL IKDEAVARGLVKNSNISADVNKKLMSVPVESVQLEQARQDNLSPDIVASLSHSPFLSVRKTLLSHYDYA WLVPTAVADELINNEDPELRERITGADLTAQQAVMLSKDKSLKVREALARTLTELKITQLSATLRTEDI ERIAEQMYLDNKENKNIVKVLLIALPEMRQLSLAKEDVHNLREGARYLTSKDVISYLLTQHDVPTVWDE LARDKLLPLEYKKQLWQRTLNLMMSKRQEDQEQAYEVQLALIDNGVVDEEMLNNAIDLLVDLPAEYRYR MRNQLFDNKELPSGIINKLDQQYRFNSDWALAVVSMKNSTRRQSERGLHRWNHEDSDIFAELATIKDKS DDEWWRALLQSRNDHLRQTALRNAHTPASLLTTLTESQDRSLAINNPQLAADVKTVWLKEDPSLLLFVD KPDLSQLRDLVKTGATRKIRNEARHRLEEKQ [SEQ ID NO: 48]