COMPOUND FOR INCREASING EFFICACY OF VIRAL VECTORS

Abstract

A compound for the sequestration of undesirable neutralizing antibodies against viral vectors in a patient. The compound includes an inert biopolymer scaffold and at least a first peptide n-mer of the general formula P ( - S - P ) .sub.(n-1) and a second peptide n-mer of the general formula P ( - S - P ) .sub.(n-1); wherein, P is a peptide with a sequence length of 2-13 amino acids and S is a non-peptide spacer, independently for each of the peptide n-mers, n is an integer of at least 1, each of the peptide n-mers is bound to the biopolymer scaffold. Independently for each occurrence, P has an amino-acid sequence including a sequence fragment with a length of at least six amino acids of a capsid protein sequence of a viral vector. Compositions including the compound and sequestering and inhibiting methods are also provided.

Claims

1. A compound comprising; a biopolymer scaffold and at least a first peptide n-mer of the general formula: $\text{P}{\left(-\text{S}-\text{P}\right)}_{\left(\text{n}-1\right)};\text{and}$ a second peptide n-mer of the general formula: $\text{P}{\left(-\text{S}-\text{P}\right)}_{\left(\text{n}-1\right)}-;$ wherein, independently for each occurrence, P is a peptide with a sequence length of 6-13 amino acids, and S is a non-peptide spacers; wherein, independently for each of the peptide n-mers, n is an integer of at least 1; wherein each of the peptide n-mers is bound to the biopolymer scaffold; wherein, independently for each occurrence, P has an amino-acid sequence comprising a sequence fragment with a length of at least six amino acids of a capsid protein sequence of a viral vector; and wherein at most three amino acids of the sequence fragment are independently substituted by any other amino acid.

2. The compound of claim 1, wherein the viral vector is an adenovirus (AdV) vector or an adeno-associated virus (AAV) vector.

3. The compound of claim 2, wherein said sequence fragment comprises a sequence of at least 6 consecutive amino acids selected from: the group of AdV sequences ETGPPTVPFLTPPF (SEQ ID NO: 32), HDSKLSIATQGPL (SEQ ID NO: 33), LNLRLGQGPLFINSAHNLDINY (SEQ ID NO: 34), VDPMDEPTLLYVLFEVFDVV (SEQ ID NO: 35), MKRARPSEDTFNPVYPYD (SEQ ID NO: 36), ISGTVQSAHLIIRFD (SEQ ID NO: 37), LGQGPLFINSAHNLDINYNKGLYLF (SEQ ID NO: 38), SYPFDAQNQLNLRLGQGPLFIN (SEQ ID NO: 39), GDTTPSAYSMSFSWDWSGHNYIN (SEQ ID NO: 40), VLLNNSFLDPEYWNFRN (SEQ ID NO: 41), HNYINEIFATSSYTFSYIA (SEQ ID NO: 42), DEAATALEINLEEEDDDNEDEVDEQAEQQKTH (SEQ ID NO: 43), INLEEEDDDNEDEVDEQAEQ (SEQ ID NO: 44), DNEDEVDEQAEQQKTHVF (SEQ ID NO: 45), EWDEAATALEINLEE (SEQ ID NO: 46), PKVVLYSEDVDIETPDTHISYMP (SEQ ID NO: 47), YIPESYKDRMYSFFRNF (SEQ ID NO: 48), DSIGDRTRYFSMW (SEQ ID NO: 49), SYKDRMYSFFRNF (SEQ ID NO: 50), and FLVQMLANYNIGYQGFY (SEQ ID NO: 51), or the group of AAV sequences WQNRDVYLQGPIWAKIP (SEQ ID NO: 52), DNTYFGYSTPWGYFDFNRFHC (SEQ ID NO: 53), MANQAKNWLPGPCY (SEQ ID NO: 54), LPYVLGSAHQGCLPPFP (SEQ ID NO: 55), NGSQAVGRSSFYCLEYF (SEQ ID NO: 56), PLIDQYLYYL (SEQ ID NO: 57), EERFFPSNGILIF (SEQ ID NO: 58), ADGVGSSSGNWHC (SEQ ID NO: 59), SEQ ID NOs: 383-1891, SEQ ID NOs: 1892-2063 and SEQ ID NOs: 2064-2103, or the group of sequences identified by SEQ ID NOs: 2104-2190.

4. The compound of claim 1, wherein at least one occurrence of P is a circularized peptide .

5. The compound of claim 1, wherein, independently for each occurrence, P is P.sub.a or P.sub.b; wherein P.sub.a has an amino-acid sequence comprising a first sequence fragment with a length of at least six amino acids of a capsid protein sequence of a viral vector, wherein at most three amino acids of the sequence fragment are independently substituted by any other amino acid; and wherein P.sub.b has an amino-acid sequence comprising a second sequence fragment with a length of at least six amino acids of a capsid protein sequence of a viral vector, wherein at most three amino acids of the sequence fragment are independently substituted by any other amino acid; and wherein the first peptide n-mer is Pa - S - P.sub.a and the second peptide n-mer is P.sub.a - S - P.sub.a-, the first peptide n-mer is P.sub.a - S - P.sub.a and the second peptide n-mer is P.sub.b - S - P.sub.b-, the first peptide n-mer is P.sub.b - S - P.sub.b and the second peptide n-mer is P.sub.b - S - P.sub.b-, the first peptide n-mer is P.sub.a - S - P.sub.b and the second peptide n-mer is P.sub.a - S - P.sub.b-, the first peptide n-mer is P.sub.a - S - P.sub.b and the second peptide n-mer is P.sub.a - S - P.sub.a-, or the first peptide n-mer is P.sub.a - S - P.sub.b and the second peptide n-mer is P.sub.b - S - P.sub.b.

6. The compound of claim 5, wherein the peptide P.sub.a and the peptide P.sub.b are two different epitopes of the same capsid antigen or two different epitope parts of the same capsid epitope.

7. The compound of claim 1, wherein the biopolymer scaffold is selected from the group consisting of albumins, alpha1-globulins, alpha2-globulins, beta-globulins and immunoglobulins, wherein the biopolymer scaffold is haptoglobin or transferrin, ; or wherein the biopolymer scaffold is an antibody specific for a CD163 protein, or a CD163-binding fragment thereof.

8. The compound of claim 1, wherein the compound is non-immunogenic in a mammal, in a human, in a non-human primate, in a sheep, in a pig, in a dog or in a rodent.

9. A pharmaceutical composition comprising the compound of claim 1 and at least one pharmaceutically acceptable excipient.

10. The pharmaceutical composition of claim 9, wherein the composition is non-immunogenic in humans.

11. The pharmaceutical composition of claim 9 for use in therapy.

12. The pharmaceutical composition for use according to claim 11, for use in increasing efficacy of a vaccine in an individual, wherein the vaccine comprises the viral vector, wherein the pharmaceutical composition is administered to the individual prior to or concurrently with administration of the vaccine.

13. The pharmaceutical composition for use according to claim 11, for use in increasing efficacy of a gene therapy composition in an individual, wherein the gene therapy composition comprises the viral vector, wherein the pharmaceutical composition is administered to the individual prior to or concurrently with administration of the gene therapy composition.

14. A method of sequestering one or more antibodies present in an individual, comprising: obtaining a pharmaceutical composition as defined in claim 9, wherein the composition is non-immunogenic in the individual and wherein the one or more antibodies present in the individual are specific for at least one occurrence of P, or for peptide P.sub.a and/or peptide P.sub.b; and administering the pharmaceutical composition to the individual.

15. A vaccine or gene therapy composition, comprising the compound of claim 1 and further comprising the viral vector and at least one pharmaceutically acceptable excipient.

16. A method of inhibiting an immune reaction to a treatment with a vaccine or a gene therapy composition in an individual in need of treatment with the vaccine or gene therapy composition, comprising: obtaining the vaccine or gene therapy composition as defined in claim 15; wherein the compound of the vaccine or gene therapy composition is non-immunogenic in the individual; and administering the vaccine or gene therapy composition to the individual.

Description

[0349] FIG. 1: SADCs successfully reduce the titre of undesired antibodies. Each SADC was applied at time point 0 by i.p. injection into Balb/c mice pre-immunized by peptide immunization against a defined antigen. Each top panel shows anti-peptide titers (0.5x dilution steps; X-axis shows log(X) dilutions) against OD values (y-axis) according to a standard ELISA detecting the corresponding antibody. Each bottom panel shows titers LogIC50 (y-axis) before injection of each SADC (i.e. titers at -48 h and -24 h) and after application of each SADC (i.e. titers +24 h, +48 h and +72 h after injection; indicated on the x-axis). (A) Compound with albumin as the biopolymer scaffold that binds to antibodies directed against EBNA1 (associated with pre-eclampsia). The mice were pre-immunized with a peptide vaccine carrying the EBNA-1 model epitope. (B) Compound with albumin as the biopolymer scaffold that binds to antibodies directed against a peptide derived from the human AChR protein MIR (associated with myasthenia gravis). The mice were pre-immunized with a peptide vaccine carrying the AChR MIR model epitope. (C) Compound with immunoglobulin as the biopolymer scaffold that binds to antibodies directed against EBNA1 (associated with pre-eclampsia). The mice were pre-immunized with a peptide vaccine carrying the EBNA-1 model epitope. (D) Compound with haptoglobin as the biopolymer scaffold that binds to antibodies directed against EBNA1 (associated with pre-eclampsia). The mice were pre-immunized with a peptide vaccine carrying the EBNA-1 model epitope. (E) Demonstration of selectivity using the same immunoglobulin-based SADC binding to antibodies directed against EBNA1 that was used in the experiment shown in panel C. The mice were pre-immunized with an unrelated amino acid sequence. No titre reduction occurred, demonstrating selectivity of the compound.

[0350] FIG. 2: SADCs are non-immunogenic and do not induce antibody formation after repeated injection into mice. Animals C1-C4 as well as animals C5-C8 were treated i.p. with two different SADCs. Control animal C was vaccinated with a KLH-peptide derived from the human AChR protein MIR. Using BSA-conjugated peptide probes T3-1, T9-1 and E005 (grey bars, as indicated in the graph), respectively, for antibody titer detection by standard ELISA at a dilution of 1:100, it could be demonstrated that antibody induction was absent in animals treated with an SADC, when compared to the vaccine-treated control animal C (y-axis, OD450 nm).

[0351] FIG. 3: Successful in vitro depletion of antibodies using SADCs carrying multiple copies of monovalent or divalent peptides. SADCs with mono- or divalent peptides were very suitable to adsorb antibodies and thereby deplete them. “Monovalent” means that peptide monomers are bound to the biopolymer scaffold (i.e. n=1) whereas “divalent” means that peptide dimers are bound to the biopolymer scaffold (i.e. n=2). In the present case, the divalent peptides were “homodivalent”, i.e. the peptide n-mer of the SADC is E006 - spacer - E006).

[0352] FIG. 4: Rapid, selective antibody depletion in mice using various SADC biopolymer scaffolds. Treated groups exhibited rapid and pronounced antibody reduction already at 24 hrs (in particular SADC-TF) when compared to the mock treated control group SADC-CTL (containing an unrelated peptide). SADC with albumin scaffold - SADC-ALB, SADC with immunoglobulin scaffold -SADC-IG, SADC with haptoglobin scaffold - SADC-HP, and SADC with transferrin scaffold - SADC-TF.

[0353] FIG. 5: Detection of SADCs in plasma via their peptide moieties 24 hrs after SADC injection. Both haptoglobin-scaffold-based SADCs (SADC-HP and SADC-CTL) exhibited a relatively shorter plasma half life which represents an advantage over SADCs with other biopolymer scaffolds such as SADC-ALB, SADC-IG oder SADC-TF. SADC with albumin scaffold - SADC-ALB, SADC with immunoglobulin scaffold - SADC-IG, SADC with haptoglobin scaffold - SADC-HP, and SADC with transferrin scaffold - SADC-TF.

[0354] FIG. 6: Detection of SADC-IgG complexes in plasma 24 hrs after SADC injection. Haptoglobin based SADCs were subject to accelerated clearance when compared to SADCs with other biopolymer scaffolds. SADC with albumin scaffold - SADC-ALB, SADC with immunoglobulin scaffold - SADC-IG, SADC with haptoglobin scaffold - SADC-HP, and SADC with transferrin scaffold - SADC-TF.

[0355] FIG. 7: In vitro analysis of SADC-IgG complex formation. Animals SADC-TF and -ALB showed pronounced immunocomplex formation and binding to C1q as reflected by the strong signals and by sharp signal lowering in case 1000 ng/ml SADC-TF due to the transition from antigen-antibody equilibrium to antigen excess. In contrast, in vitro immunocomplex formation with SADC-HP or SADC-IG were much less efficient when measured in the present assay. These findings corroborate the finding that haptoglobin scaffolds are advantageous over other SADC biopolymer scaffolds because of the reduced propensity to activate the complement system. SADC with albumin scaffold - SADC-ALB, SADC with immunoglobulin scaffold - SADC-IG, SADC with haptoglobin scaffold - SADC-HP, and SADC with transferrin scaffold - SADC-TF.

[0356] FIG. 8: Determination of IgG capturing by SADCs in vitro. SADC-HP showed markedly less antibody binding capacity in vitro when compared to SADC-TF or SADC-ALB. SADC with albumin scaffold -SADC-ALB, SADC with immunoglobulin scaffold - SADC-IG, SADC with haptoglobin scaffold - SADC-HP, and SADC with transferrin scaffold - SADC-TF.

[0357] FIG. 9: Blood clearance of an anti-CD163-antibody-based biopolymer scaffold. In a mouse model, mAb E10B10 (specific for murine CD163) is much more rapidly cleared from circulation than mAb Mac2-158 (specific for human CD163 but not for murine CD163, thus serving as negative control in this experiment).

[0358] FIG. 10: AdV capsid protein sequences for use in the present invention. Databases accession numbers (in particular UniProt or GenBank accession numbers) are listed.

[0359] FIG. 11: AAV capsid protein sequences for use in the present invention. Databases accession numbers (in particular UniProt or GenBank accession numbers are listed), as well as references to sequences in patent publications.

EXAMPLES

[0360] Examples 1-3, 5-8 and 11-13 demonstrate that SADCs are very well suited for selective removal of undesirable antibodies. Examples 4, 10 and 14-21 contain more details on the inventive compounds with respect to antibodies against viral vectors and corresponding peptide epitopes.

Example 1: SADCs Effectively Reduce the Titre of Undesired Antibodies.

[0361] Animal models: In order to provide in vivo models with measurable titers of prototypic undesired antibodies in human indications, BALB/c mice were immunized using standard experimental vaccination with KLH-conjugated peptide vaccines derived from established human autoantigens or anti-drug antibodies. After titer evaluation by standard peptide ELISA, immunized animals were treated with the corresponding test SADCs to demonstrate selective antibody lowering by SADC treatment. All experiments were performed in compliance with the guidelines by the corresponding animal ethics authorities.

[0362] Immunization of mice with model antigens: Female BALB/c mice (aged 8-10 weeks) were supplied by Janvier (France), maintained under a 12 h light/12 h dark cycle and given free access to food and water. Immunizations were performed by s.c. application of KLH carrier-conjugated peptide vaccines injected 3 times in biweekly intervals. KLH conjugates were generated with peptide T3-2 (SEQ ID NO. 356: CGRPQKRPSCIGCKG), which represents an example for molecular mimicry between a viral antigen (EBNA-1) and an endogenous human receptor antigen, namely the placental GPR50 protein, that was shown to be relevant to preeclampsia (Elliott et al.). In order to confirm the generality of this approach, a larger antigenic peptide derived from the autoimmune condition myasthenia gravis was used for immunization of mice with a human autoepitope. In analogy to peptide T3-2, animals were immunized with peptide T1-1 (SEQ ID NO. 357: LKWNPDDYGGVKKIHIPSEKGC), derived from the MIR (main immunogenic region) of the human AChR protein which plays a fundamental role in pathogenesis of the disease (Luo et al.). The T1-1 peptide was used for immunizing mice with a surrogate partial model epitope of the human AChR autoantigen. The peptide T8-1 (SEQ ID NO. 358: DHTLYTPYHTHPG) was used to immunize control mice to provide a control titer for proof of selectivity of the system. For vaccine conjugate preparation, KLH carrier (Sigma) was activated with sulfo-GMBS (Cat. Nr. 22324 Thermo), according to the manufacturer’s instructions, followed by addition of either N- or C-terminally cysteinylated peptides T3-2 and T1-1 and final addition of Alhydrogel.sup.® before injection into the flank of the animals. The doses for vaccines T3-2 and T1-1 were 15 .Math.g of conjugate in a volume of 100 ul per injection containing Alhydrogel.sup.® (InvivoGen VAC-Alu-250) at a final concentration of 1% per dose.

[0363] Generation of prototypic SADCs: For testing selective antibody lowering activity by SADCs of T3-2 and T1-1 immunized mice, SADCs were prepared with mouse serum albumin (MSA) or mouse immunoglobulin (mouse-Ig) as biopolymer scaffold in order to provide an autologous biopolymer scaffold, that will not induce any immune reaction in mice, or non-autologuous human haptoglobin as biopolymer scaffold (that did not induce an allogenic reaction after one-time injection within 72 hours). N-terminally cysteinylated SADC peptide E049 (SEQ ID NO. 359: GRPQKRPSCIG) and/or C-terminally cysteinylated SADC peptide E006 (SEQ ID NO. 360: VKKIHIPSEKG) were linked to the scaffold using sulfo-GMBS (Cat. Nr. 22324 Thermo)-activated MSA (Sigma; Cat. Nr. A3559) or -mouse-Ig (Sigma, I5381) or -human haptoglobin (Sigma H0138) according to the instructions of the manufacturer, thereby providing MSA-, Ig- and haptoglobin-based SADCs with the corresponding cysteinylated peptides, that were covalently attached to the lysines of the corresponding biopolymer scaffold. Beside conjugation of the cysteinylated peptides to the lysines via a bifunctional amine-to-sulfhydryl crosslinker, a portion of the added cysteinylated SADC peptides directly reacted with sulfhydryl groups of cysteins of the albumin scaffold protein, which can be detected by treating the conjugates with DTT followed by subsequent detection of free peptides using mass spectrometry or any other analytical method that detects free peptide. Finally, these SADC conjugates were dialysed against water using Pur-A-Lyzer™ (Sigma) and subsequently lyophilized. The lyophilized material was resuspended in PBS before injection into animals.

[0364] In vivo functional testing of SADCs: Prototypic SADCs, SADC-E049 and SADC-E006 were injected intraperitoneally (i.p.; as a surrogate for an intended intravenous application in humans and larger animals) into the mice that had previously been immunized with peptide vaccine T3-2 (carrying the EBNA-1 model epitope) and peptide vaccine T1-1 (carrying the AChR MIR model epitope). The applied dose was 30 .Math.g SADC conjugate in a volume of 50 .Math.l PBS. Blood takes were performed by submandibular vein puncture, before (-48 h, -24 h) and after (+24 h,+48 h,+72 h, etc.) i.p. SADC injections, respectively, using capillary micro-hematocrit tubes. Using ELISA analysis (see below), it was found that both prototypic SADCs were able to clearly reduce the titers over a period of at least 72 hrs in the present animal model. It could therefore be concluded that SADCs can be used to effectively reduce titers in vivo.

[0365] Titer analysis: Peptide ELISAs were performed according to standard procedures using 96-well plates (Nunc Medisorp plates; Thermofisher, Cat Nr 467320) coated for 1 h at RT with BSA-coupled peptides (30 nM, dissolved in PBS) and incubated with the appropriate buffers while shaking (blocking buffer, 1% BSA, 1x PBS; washing buffer, 1xPBS / 0,1% Tween; dilution buffer, 1xPBS / 0.1% BSA /0,1% Tween). After serum incubation (dilutions starting at 1:50 in PBS; typically in 1:3 or 1:2 titration steps), bound antibodies were detected using Horseradish Peroxidase-conjugated goat anti-mouse IgG (Fc) from Jackson immunoresearch (115-035-008). After stopping the reaction, plates were measured at 450 nm for 20 min using TMB. EC50 were calculated from readout values using curve fitting with a 4-parameter logistic regression model (GraphPad Prism) according to the procedures recommended by the manufacturer. Constraining parameters for ceiling and floor values were set accordingly, providing curve fitting quality levels of R.sup.2 >0.98.

[0366] FIG. 1A shows an in vivo proof of concept in a mouse model for in vivo selective plasma-lowering activity of a prototypic albumin-based SADC candidate that binds to antibodies directed against EBNA1, as a model for autoantibodies and mimicry in preeclampsia (Elliott et al.). For these mouse experiments, mouse albumin was used, in order to avoid any reactivity against a protein from a foreign species. Antibody titers were induced in 6 months old Balb/c mice by standard peptide vaccination. The bottom panel demonstrates that titers LogIC50 (y-axis) before SADC injection (i.e. titers at -48 h and -24 h) were higher than titers LogIC50 after SADC application (i.e. titers +24 h, +48 h and +72 h after injection; indicated on the x-axis).

[0367] A similar example is shown in FIG. 1B, using an alternative example of a peptidic antibody binding moiety for a different disease indication. Antibody lowering activity of an albumin-based SADC in a mouse model that was pre-immunized with a different peptide derived from the human AChR protein MIR region (Luo et al.) in order to mimic the situation in myasthenia gravis. The induced antibody titers against the AChR-MIR region were used as surrogate for anti-AChR-MIR autoantibodies known to play a causative role in myasthenia gravis (reviewed by Vincent et al.). A clear titer reduction was seen after SADC application.

[0368] FIGS. 1C and 1D demonstrate the functionality of SADC variants comprising alternative biopolymer scaffolds. Specifically, FIG. 1C shows that an immunoglobulin scaffold can be successfully used whereas FIG. 1D demonstrates the use of a haptoglobin-scaffold for constructing an SADC. Both examples show an in vivo proof of concept for selective antibody lowering by an SADC, carrying covalently bound example peptide E049.

[0369] The haptoglobin-based SADC was generated using human Haptoglobin as a surrogate although the autologuous scaffold protein would be preferred. In order to avoid formation of antihuman-haptoglobin antibodies, only one single SADC injection per mouse of the non-autologuous scaffold haptoglobin was used for the present experimental conditions. As expected, under the present experimental conditions (i.e. one-time application), no antibody reactivity was observed against the present surrogate haptoglobin homologue.

[0370] FIG. 1E demonstrates the selectivity of the SADC system. The immunoglobulin-based SADC carrying the peptide E049 (i.e. the same as in FIG. 1C) cannot reduce the Ig-titer that was induced by a peptide vaccine with an unrelated, irrelevant amino acid sequence, designated peptide T8-1 (SEQ ID NO. 358: DHTLYTPYHTHPG). The example shows an in vivo proof of concept for the selectivity of the system. The top panel shows anti-peptide T8-1 titers (0,5x dilution steps starting from 1:50 to 1:102400; X-axis shows log(X) dilutions) against OD values (y-axis) according to a standard ELISA. T8-1-titers are unaffected by administration of SADC-Ig-E049 after application. The bottom panel demonstrates that the initial titers LogIC50 (y-axis) before SADC injection (i.e. titers at -48 h and -24 h) are unaffected by administration of SADC-Ig-E049 (arrow) when compared to the titers LogIC50 after SADC application (i.e. titers +24 h, +48 h and +72 h; as indicated on the x-axis), thereby demonstrating the selectivity of the system.

Example 2: Immunogenicity of SADCs

[0371] In order to exclude immunogenicity of SADCs, prototypic candidate SADCs were tested for their propensity to induce antibodies upon repeated injection. Peptides T3-1 and T9-1 were used for this test. T3-1 is a 10-amino acid peptide derived from a reference epitope of the Angiotensin receptor, against which agonistic autoantibodies are formed in a pre-eclampsia animal model (Zhou et al.); T9-1 is a 12-amino acid peptide derived from a reference anti-drug antibody epitope of human IFN gamma (Lin et al.). These control SADC conjugates were injected 8 x every two weeks i.p. into naive, non-immunized female BALB/c mice starting at an age of 8-10 weeks.

[0372] Animals C1-C4 were treated i.p. (as described in example 1) with SADC T3-1. Animals C5-C8 were treated i.p. with an SADC carrying the peptide T9-1. As a reference signal for ELISA analysis, plasma from a control animal that was vaccinated 3 times with KLH-peptide T1-1 (derived from the AChR-MIR, explained in Example 1) was used. Using BSA-conjugated peptide probes T3-1, T9-1 and E005 (SEQ ID NO. 361: GGVKKIHIPSEK), respectively, for antibody titer detection by standard ELISA at a dilution of 1:100, it could be demonstrated that antibody induction was absent in SADC-treated animals, when compared to the vaccine-treated control animal C (see FIG. 2). The plasmas were obtained by submandibular blood collection, 1 week after the 3rd vaccine injection (control animal C) and after the last of 8 consecutive SADC injections in 2-weeks intervals (animals C1-C8), respectively. Thus it was demonstrated that SADCs are non-immunogenic and do not induce antibody formation after repeated injection into mice.

Example 3: Successful In Vitro Depletion of Antibodies Using SADCs Carrying Multiple Copies of Monovalent or Divalent Peptides.

[0373] Plasma of E006-KLH (VKKIHIPSEKG (SEQ ID NO: 360) with C-terminal cysteine, conjugated to KLH) vaccinated mice was diluted 1:3200 in dilution buffer (PBS + 0.1% w/v BSA + 0.1% Tween20) and incubated (100 .Math.l, room temperature) sequentially (10 min/well) four times on single wells of a microtiter plate that was coated with 2.5 .Math.g/ml (250 ng/well) of SADC or 5 .Math.g/ml (500 ng/well) albumin as negative control.

[0374] In order to determine the amount of free, unbound antibody present before and after incubation on SADC coated wells, 50 .Math.l of the diluted serum were taken before and after the depletion and quantified by standard ELISA using E006-BSA coated plates (10 nM peptide) and detection by goat anti mouse IgG bio (Southern Biotech, diluted 1:2000). Subsequently, the biotinylated antibody was detected with Streptavidin-HRP (Thermo Scientific, diluted 1:5000) using TMB as substrate. Development of the signal was stopped with 0.5 M sulfuric acid.

[0375] ELISA was measured at OD450nm (y-axis). As a result, the antibody was efficiently adsorbed by either coated mono- or divalent SADCs containing peptide E006 with C-terminal cysteine (sequence VKKIHIPSEKGC, SEQ ID NO: 362) (before=non-depleted starting material; mono- divalent corresponds to peptides displayed on the SADC surface; neg. control was albumin; indicated on the x-axis). See FIG. 3. (“Monovalent” means that peptide monomers are bound to the biopolymer scaffold (i.e. n=1) whereas “divalent” means that peptide dimers are bound to the biopolymer scaffold (i.e. n=2). In the present case, the divalent peptides were “homodivalent”, i.e. the peptide n-mer of the SADC is E006 - S - E006.)

[0376] This demonstrates that SADCs with mono- or divalent peptides are very suitable to adsorb antibodies and thereby deplete them.

Example 4: Generation of Mimotope-Based SADCs

[0377] mAb 4D2 is a mouse IgG2a mAb targeting the adenovirus fiber epitope peptide (NCBI Reference Sequence: AP_000226.1). It represents a prototype neutralizing antibody that was generated from UV irradiated Ad2 virus (Krasnykh et al, 1998).

[0378] Linear and circular peptides derived from wild-type or modified peptide amino acid sequences can be used for the construction of specific SADCs for the selective removal of neutralizing antibodies against viral vectors. In case of a particular epitope, linear peptides or constrained peptides such as cyclopeptides containing portions of an epitope or variants thereof, where for example, one or several amino acids have been substituted or chemically modified in order to improve affinity to an antibody (mimotopes), can be used for constructing SADCs. A peptide screen can be performed with the aim of identifying peptides with optimized affinity to neutralizing antibodies. The flexibility of structural or chemical peptide modification provided a solution to minimize the risk of immunogenicity, in particular of binding of the peptide to HLA and thus the risk of unwanted immune stimulation.

[0379] Therefore, wild-type as well as modified linear and circular peptide sequences are derived from an epitope of a viral capsid protein as disclosed herein, e.g. the epitopic sequence LNLRLGQGPLFINSAHNLDINY (SEQ ID NO: 34) of mAb 4D2 found in the course of the present invention (see example further below). Peptides of various length and positions are systematically permutated by amino acid substitutions and synthesized on a peptide array. This allows screening of 60000 circular and linear wild-type and mimotope peptides derived from these sequences. The peptide arrays are incubated with mAb 4D2. This antibody is therefore used to screen the 60000 peptides and 100 circular and 100 linear peptide hits are selected based on their relative binding strength to the antibody. Of these 200 peptides, 51 sequences are identical between the circular and the linear peptide group. All of the best peptides identified have at least one amino acid substitution when aligned to the original sequences, respectively and are therefore regarded as mimotopes. Also, higher binding strengths can be achieved with circularized peptides.

[0380] These newly identified peptides, preferentially those with high relative binding values, are used to generate SADCs for increasing efficacy of AdV-based vector vaccines.

Example 5: Rapid, Selective Antibody Depletion in Mice Using Various SADC Biopolymer Scaffolds.

[0381] 10 .Math.g of model undesired antibody mAb anti V5 (Thermo Scientific) was injected i.p. into female Balb/c mice (5 animals per treatment group; aged 9-11 weeks) followed by intravenous injection of 50 .Math.g SADC (different biopolymer scaffolds with tagged V5 peptides bound, see below) 48 hrs after the initial antibody administration. Blood was collected at 24 hrs intervals from the submandibular vein. Blood samples for time point 0 hrs were taken just before SADC administration.

[0382] Blood was collected every 24 hrs until time point 120 hrs after the SADC administration (x-axis). The decay and reduction of plasma anti-V5 IgG levels after SADC administration was determined by anti V5 titer readout using standard ELISA procedures in combination with coated V5-peptide-BSA (peptide sequence IPNPLLGLDC - SEQ ID NO: 561) and detection by goat anti mouse IgG bio (Southern Biotech, diluted 1:2000) as shown in FIG. 4. In addition, SADC levels (see Example 6) and immunocomplex formation (see Example 7) were analyzed.

[0383] EC50[OD450] values were determined using 4 parameter logistic curve fitting and relative signal decay between the initial level (set to 1 at time point 0) and the following time points (x-axis) was calculated as ratio of the EC50 values (y-axis, fold signal reduction EC50). All SADC peptides contained tags for direct detection of SADC and immunocomplexes from plasma samples; peptide sequences used for SADCs were: IPNPLLGLDGGSGDYKDDDDKGK(SEQ ID NO: 363)-(BiotinAca)GC (SADC with albumin scaffold - SADC-ALB, SADC with immunoglobulin scaffold -SADC-IG, SADC with haptoglobin scaffold - SADC-HP, and SADC with transferrin scaffold - SADC-TF) and unrelated peptide VKKIHIPSEKGGSGDYKDDDDKGK(SEQ ID NO: 364)-(BiotinAca)GC as negative control SADC (SADC-CTR).

[0384] The SADC scaffolds for the different treatment groups of 5 animals are displayed in black/grey shades (see inset of FIG. 4).

[0385] Treated groups exhibited rapid and pronounced anibody reduction already at 24 hrs (in particular SADC-TF) when compared to the mock treated control group SADC-CTL. SADC-CTR was used as reference for a normal antibody decay since it has no antibody lowering activity because its peptide sequence is not recognized by the administered anti V5 antibody. The decay of SADC-CTR is thus marked with a trend line, emphasizing the antibody level differences between treated and mock treated animals.

[0386] In order to determine the effectivity of selective antibody lowering under these experimental conditions, a two-way ANOVA test was performed using a Dunnett’s multiple comparison test. 48 hrs after SADC administration, the antibody EC50 was highly significantly reduced in all SADC groups (p<0.0001) compared to the SADC-CTR reference group (trend line). At 120 hrs after SADC administration, antibody decrease was highly significant in the SADC-ALB and SADC-TF groups (both p<0.0001) and significant in the SADC-HP group (p=0.0292), whereas the SADC-IG group showed a trend towards an EC50 reduction(p = 0.0722) 120 hrs after SADC administration. Of note, selective antibody reduction was highly significant (p<0.0001) in the SADC-ALB and SADC-TF groups at all tested time-points after SADC administration.

[0387] It is concluded that all SADC biopolymer scaffolds were able to selectively reduce antibody levels. Titer reduction was most pronounced with SADC-ALB and SADC-TF and no rebound or recycling of antibody levels was detected towards the last time points suggesting that undesired antibodies are degraded as intended.

Example 6: Detection of SADCs in Plasma 24 hrs after SADC Injection.

[0388] Plasma levels of different SADC variants at 24 hrs after i.v. injection into Balb/c mice. Determination of Plasma levels (y-axis) of SADC-ALB, -IG, -HP, -TF and the negative control SADC-CTR (x-axis), were detected in the plasmas from the animals already described in example 5. Injected plasma SADC levels were detected by standard ELISA whereby SADCs were captured via their biotin moieties of their peptides in combination with streptavidin coated plates (Thermo Scientific). Captured SADCs were detected by mouse anti Flag-HRP antibody (Thermo Scientific, 1:2,000 diluted) detecting the Flag-tagged peptides (see also example 7):

[0389] Assuming a theoretical amount in the order of 25 .Math.g/ml in blood after injecting 50 .Math.g SADC i.v., the detectable amount of SADC ranged between 799 and 623 ng/ml for SADC-ALB or SADC-IG and up to approximately 5000 ng/ml for SADC-TF, 24 hrs after SADC injection. However surprisingly and in contrast, SADC-HP and control SADC-CTR (which is also a SADC-HP variant, however carrying the in this case unrelated negative control peptide E006, see previous examples), had completely disappeared from circulation 24 hrs after injection, and were not detectable anymore. See FIG. 5.

[0390] This demonstrates that both Haptoglobin scaffold-based SADCs tested in the present example ((namely SADC-HP and SADC-CTR) exhibit a relatively shorter plasma half-life which represents an advantage over SADCs such as SADC-ALB, SADC-IG oder SADC-TF in regard of their potential role in complement-dependent vascular and renal damage due to the in vivo risk of immunocomplex formation. Another advantage of SADC-HP is the accelerated clearance rate of their unwanted target antibody from blood in cases where a rapid therapeutic effect is needed. The present results demonstrate that Haptoglobin-based SADC scaffolds (as represented by SADC-HP and SADC-CTR) are subject to rapid clearance from the blood, regardless of whether SADC-binding antibodies are present in the blood, thereby minimizing undesirable immunocomplex formation and showing rapid and efficient clearance. Haptoglobin-based SADCs such as SADC-HP in the present example thus provide a therapeutically relevant advantage over other SADC biopolymer scaffolds, such as demonstrated by SADC-TF or SADC-ALB, both of which are still detectable 24 hrs after injection under the described conditions, in contrast to SADC-HP or SADC-CTR which both are completely cleared 24 hrs after injection.

Example 7: Detection of SADC-IgG Complexes in Plasma 24 hrs After SADC Injection.

[0391] In order to determine the amount IgG bound to SADCs in vivo, after i.v. injection of 10 .Math.g anti V5 IgG (Thermo Scientific) followed by injection of SADC-ALB, -HP, -TF and -CTR (50 .Math.g) administered i.v. 48 h after antibody injection, plasma was collected from the submandibular vein, 24 hrs after SADC injection, and incubated on streptavidin plates for capturing SADCs from plasma via their biotinylated SADC-V5-peptide [IPNPLLGLDGGSGDYKDDDDKGK(SEQ ID NO: 363) (BiotinAca)GC or in case of SADC-CTR the negative control peptide VKKIHIPSEKGGSGDYKDDDDKGK(SEQ ID NO: 364) (BiotinAca)GC]. IgG bound to the streptavidin-captured SADCs was detected by ELISA using a goat anti mouse IgG HRP antibody (Jackson Immuno Research, diluted 1:2,000) for detection of the SADC-antibody complexes present in plasma 24 hrs after SADC injection. OD450nm values (y-axis) obtained for a negative control serum from untreated animals were subtracted from the OD450nm values of the test groups (x-axis) for background correction.

[0392] As shown in FIG. 6, pronounced anti-V5 antibody signals were seen in case of SADC-ALB and SADC-TF injected mice (black bars represent background corrected OD values at a dilution of 1:25, mean value of 5 mice; standard deviation error bars), whereas no antibody signal could be detected in plasmas from SADC-HP or control SADC-CTR injected animals (SADC-CTR is a negative control carrying the irrelevant peptide bio-FLG-E006 [VKKIHIPSEKGGSGDYKDDDDKGK(SEQ ID NO: 364) (BiotinAca)GC] that is not recognized by any anti V5 antibody). This demonstrates the absence of detectable amounts of SADC-HP/IgG complexes in the plasma 24 hrs after i.v. SADC application.

[0393] SADC-HP is therefore subject to accelerated clearance in anti V5 pre-injected mice when compared to SADC-ALB or SADC-TF.

Example 8: In Vitro Analysis of SADC-Immunoglobulin Complex Formation

[0394] SADC-antibody complex formation was analyzed by preincubating 1 .Math.g/ml of human anti V5 antibody (anti V5 epitope tag [SV5-P-K], human IgG3, Absolute Antibody) with increasing concentrations of SADC-ALB, -IG, -HP, -TF and -CTR (displayed on the x-axis) in PBS +0.1% w/v BSA + 0.1% v/v Tween20 for 2 hours at room temperature in order to allow for immunocomplex formation in vitro. After complex formation, samples were incubated on ELISA plates that had previously been coated with 10 .Math.g/ml of human C1q (CompTech) for 1 h at room temperature, in order to allow capturing of in vitro formed immunocomplexes. Complexes were subsequently detected by ELISA using anti human IgG (Fab specific)-Peroxidase (Sigma, diluted 1:1,000). Measured signals at OD450 nm (y-axis) reflect Antibody-SADC complex formation in vitro.

[0395] As shown in FIG. 7, SADC-TF and -ALB showed pronounced immunocomplex formation and binding to C1q as reflected by the strong signals and by sharp signal lowering in case 1000 ng/ml SADC-TF due to the transition from antigen-antibody equilibrium to antigen excess. In contrast, in vitro immunocomplex formation with SADC-HP or SADC-IG were much less efficient when measured in the present assay.

[0396] Together with the in vivo data (previous examples), these findings corroborate the finding that haptoglobin scaffolds are advantageous over other SADC biopolymer scaffolds because of the reduced propensity to activate the complement system. In contrast, SADC-TF or SADC-ALB show higher complexation, and thereby carry a certain risk of activating the C1 complex with initiation of the classical complement pathway (a risk which may be tolerable in some settings, however).

Example 9: Determination of IgG Capturing by SADCs In Vitro

[0397] Immunocomplexes were allowed to form in vitro, similar to the previous example, using 1 .Math.g/ml mouse anti V5 antibody (Thermo Scientific) in combination with increasing amounts of SADCs (displayed on the x-axis). SADC-antibody complexes were captured on a streptavidin coated ELISA plate via the biotinylated SADC-peptides (see previous examples), followed by detection of bound anti-V5 using anti mouse IgG-HRP (Jackson Immuno Research, diluted 1:2,000).

[0398] Under these assay conditions, SADC-HP showed markedly less antibody binding capacity in vitro when compared to SADC-TF or SADC-ALB (see FIG. 8, A). The calculated EC50 values for IgG detection on SADCs were 7.0 ng/ml, 27.9 ng/ml and 55.5 ng/ml for SADC-TF, -ALB and -HP, respectively (see FIG. 8, B).

[0399] This in vitro finding is consistent with the observation (see previous examples) that SADC-HP has a lower immunocomplex formation capacity when compared to SADC-TF or SADC-ALB which is regarded as a safety advantage with respect to its therapeutic use for the depletion of unwanted antibodies.

Example 10: SADCs to Reduce Undesired Antibodies Against AAV-8

[0400] Three SADCs are provided to reduce AAV-8-neutralizing antibodies which hamper gene therapy (see Gurda et al. for the epitopes used; see also AAV-8 capsid protein sequence UniProt Q8JQF8, sequence version 1): [0401] (a) SADC-a with Mac2-158 (as disclosed in WO 2011/039510 A2) as biopolymer scaffold and at least two peptides with the sequence YLQGPIW (SEQ ID NO: 312) covalently bound to the scaffold, [0402] (b) SADC-b with human transferrin as biopolymer scaffold and at least two peptides with the sequence YFGYSTPWGYFDF (SEQ ID NO: 320) covalently bound to the scaffold, and [0403] (c) SADC-c with human albumin as biopolymer scaffold and at least two peptides with the sequence QGCLPPF (SEQ ID NO: 335) covalently bound to the scaffold.These SADCs are administered to an individual who will undergo gene therapy with AAV-8 as vector in order to increase efficiency of the gene therapy.

Example 11: In-Vivo Function of Anti-CD163-Antibody-Based SADC Biopolymer Scaffold

[0404] Rapid in vivo blood clearance of anti-mouse-CD163 mAb E10B10 (as disclosed in WO 2011/039510 A2). mAb E10B10 was resynthesized with a mouse IgG2a backbone. 50 .Math.g mAb E10B10 and Mac2-158 (human-specific anti-CD163 mAb as disclosed in WO 2011/039510 A2, used as negative control in this example since it does not bind to mouse CD163) were injected i.v. into mice and measured after 12, 24, 36, 48, 72, 96 hours in an ELISA to determine the blood clearance.

[0405] mAb E10B10 was much more rapidly cleared from circulation than control mAb Mac2-158 was, as shown in FIG. 9, since E10B10 binds to the mouse CD163 whereas Mac2-158 is human-specific, although both were expressed as mouse IgG2a isotypes for direct comparison.

[0406] In conclusion, anti-CD163 antibodies are highly suitable as SADC scaffold because of their clearance profile. SADCs with such scaffolds will rapidly clear undesirable antibodies from circulation.

[0407] Detailed methods: 50 ug of biotinylated monoclonal antibodies E10B10 and biotinylated Mac2-158 were injected i.v. into mice and measured after 12, 24, 36, 48, 72, 96 hours to determine the clearance by ELISA: Streptavidin plates were incubated with plasma samples diluted in PBS + 0.1%BSA + 0.1% Tween20 for 1 h at room temperature (50 .Math.l/well). After washing (3x with PBS + 0.1% Tween20), bound biotinylated antibodies were detected with anti-mouse IgG+IgM-HRP antibody at a 1:1000 dilution. After washing, TMB substrate was added and development of the substrate was stopped with TMB Stop Solution. The signal at OD450 nm was read. The EC50 values were calculated by nonlinear regression using 4 parametric curve fitting with constrained curves and least squares regression. EC50 values at time-point T12 (this was the first measured time-point after antibody injection) was set at 100%, all other EC50 values were compared to the levels at T12.

Example 12: Epitope Mapping of Anti-CD163 mAbs

[0408] mAb E10B10 provides CD163-mediated, accelerated in vivo clearance from blood in mice (see example 11). The epitope of this antibody was fine mapped using circular peptide arrays, whereby the peptides were derived from mouse CD163. As a result, a peptide cluster that is recognized by mAb E10B10 was identified (see example 13).

[0409] The same epitope mapping procedure using circularized peptides was performed with mAb Mac2-158 (as disclosed in WO 2011/039510 A2). Epitope mapping results for mAb Mac2-158 yielded two peptide clusters (see example 13) which allowed further demarcation of CD163 epitope regions that are especially relevant to internalization of ligands and antibodies that bind to the receptor.

[0410] These newly characterized epitopes for Mac2-158 and E10B10 thus revealed three preferred binding regions for antibodies against CD163. Based on the fine epitope mapping work, linear or preferentially circular peptides are synthesized and used for the induction, production and selection of polyclonal or monoclonal antibodies or other CD163-binding SADC scaffolds that target CD163.

Example 13: Epitope Mapping of Anti-CD163 mAbs

[0411] Peptides aligned to SRCR domain 1 of human CD163 were selected from the top 20 peptide hits of mAb Mac2-158 circular epitope mapping peptides and the most preferred sequences were selected from two peptide alignment clusters at the N-terminus and at the C-terminus of SRCR-1 of human CD163. As a result, the following sequences (as well as motifs derived therefrom) are highly suitable epitopes anti-CD163 antibodies and fragments thereof used as SADC biopolymer scaffold:

TABLE-US-00004 Peptide cluster 1: 04 ----------------EWGTVCNNGWSME------- (SEQ ID NO: 7) 07 -----CSGRVEVKVQEEW------------------ (SEQ ID NO: 365) 09 --------------QEEWGTVCNNGWS--------- (SEQ ID NO: 8) 12 -----------------WGTVCNNGWSMEA------ (SEQ ID NO: 9) 14 ---------------EEWGTVCNNGWSM-------- (SEQ ID NO: 10) 18 -------------VQEEWGTVCNNGW---------- (SEQ ID NO: 11) 19 ----------------EWGTVCNNGW---------- (SEQ ID NO: 12) 20 -----------------WGTVCNNGWS--------- (SEQ ID NO: 5) huCD163-domain 1-3 DGENKCSGRVEVKVQEEWGTVCNNGWSMEAVSVICN (SEQ ID NO: 366)

TABLE-US-00005 Peptide cluster 2: 01 ------------ESALWDC-------------- (SEQ ID NO: 15) 02 ---------RGNESALWDC-------------- (SEQ ID NO: 16) 03 -------SCRGNESALW---------------- (SEQ ID NO: 17) 05 ------VSCRGNESALWDC-------------- (SEQ ID NO: 18) 06 --------------ALWDCKHDGW--------- (SEQ ID NO. 19) 08 ----DHVSCRGNESALW---------------- (SEQ ID NO. 20) 11 --------CRGNESALWD--------------- (SEQ ID NO. 21) 13 -----------NESALWDCKHDGW--------- (SEQ ID NO. 22) 17 ------------ESALWDCKHDGWG-------- (SEQ ID NO. 23) huCD163-domain1-3 RIWMDHVSCRGNESALWDCKHDGWGKHSNCTHQ (SEQ ID NO: 367)

[0412] Fine epitope mapping of mAb E10B10 was performed as for Mac2-158. 1068 circular peptides (sized 7, 10 and 13 amino acids) and derived from SRCR-1 to -3 of the mouse CD163 sequence (UniProKB Q2VLH6.2) were screened with mAb E10B10 and the following top binding peptides were obtained (ranked by relative signal strength). The human CD163 sequence was aligned to this cluster of mouse CD163 sequences, revealing another highly suitable epitope:

TABLE-US-00006 Peptide cluster 3: 01 ---------------------VTNAPGEMKKELR--------- (SEQ ID NO: 368) 02 ------------------ASAVTNAPGEMKK------------ (SEQ ID NO: 369) 03 ---------------------VTNAPGEMKK------------ (SEQ ID NO: 370) 04 ---------------------VTNAPGE--------------- (SEQ ID NO: 371) 05 ----------------GSASAVTNAPGEM-------------- (SEQ ID NO: 372) 06 --------------------AVTNAPGEMKKEL---------- (SEQ ID NO: 373) 07 -----------------SASAVTNAPGEMK------------- (SEQ ID NO: 374) 08 ---------------SGSASAVTNAPGE--------------- (SEQ ID NO: 375) 09 --------------------AVTNAPGEMK------------- (SEQ ID NO: 376) 10 -------------------SAVTNAPGEM-------------- (SEQ ID NO: 377) 11 ------------------ASAVTNAPGE--------------- (SEQ ID NO: 378) 12 -------------------SAVTNAPGEMKKE----------- (SEQ ID NO: 379) 13 ----------------------TNAPGEMKKE----------- (SEQ ID NO: 380) mCD163(SRCR-1, N-terminus) VTNAPGEMKKELRLAGGENNCS (SEQ ID NO: 75) hCD163(SRCR-1, N-terminus) SSLGGTDKELRLVDGENKCS (SEQ ID NO: 24)

[0413] The human homologues of mouse peptides 01 - 13 from cluster 3 have the following sequences of the N-terminal portion of the mature human CD163 protein (UniProtKB: Q86VB7):

TABLE-US-00007 Cluster 3 peptides (mouse): human homologues: 01 SSLGGTDKELR (SEQ ID NO: 25) 06 SSLGGTDKEL (SEQ ID NO: 27) 12,13 SSLGGTDKE (SEQ ID NO: 28) 02,03 SSLGGTDK (SEQ ID NO: 29) 07,09 SSLGGTD (SEQ ID NO: 30) 05,10 SSLGGT (SEQ ID NO: 31) 04,08,11 SSLGG (SEQ ID NO: 26) hCD163 (SRCR-1) SSLGGTDKELRLVDGENKCS (SEQ ID NO: 24)

[0414] These homologue peptides represent further highly suitable epitopes for the anti-CD163 antibody-based biopolymer scaffold.

Example 14: Epitope Mapping of mAb 4D2 Against AdV

[0415] mAb 4D2 is a mouse IgG2a mAb targeting the adenovirus fiber epitope peptide (NCBI Reference Sequence: AP_000226.1). It represents a prototype neutralizing antibody that was generated from UV irradiated Ad2 virus (Krasnykh et al, 1998). In order to obtain cyclic antibody binding peptides from the virus neutralizing epitope, mAb 4D2 was mapped against aligned cyclic peptides derived from the fiber sequence. The sequence at amino acid positions 1 to 581 of NCBI Reference Sequence: AP_000226.1 was used as a starting sequence for designing 7mer, 10mer and 13mer cyclic peptides that were then synthesized and circularized directly on a peptide microarray and subsequently incubated with various concentrations of the antibody. The binding signal of monoclonal antibody 4D2 to the peptides yielded several binding hits that were be aligned against the sequence of the protein and subsequently clustered. The resulting clusters were designated cluster1 (length=14 amino acids), cluster2 (length=13 amino acids) and cluster3 (length=22 amino acids). Below are the aligments of the corresponding new peptides that are able to bind the mAb 4D2 paratope. The number of the peptide names corresponds to the rank of the binding signal of the antibody to the microarray (i.e. peptide 01 binds strongest, 02 second strongest, etc.). A selection of top candidate binding peptides out of the top 50 top binders was aligned against the corresponding protein sequence (first line).

TABLE-US-00008 cluster1 ETGPPTVPFLTPPF (SEQ ID NO: 32) 08 --GPPTVPFLTP-- (SEQ ID NO: 60) 10 ETGPPTVPFLTPP- (SEQ ID NO: 61) 21 -TGPPTVPFLT--- (SEQ ID NO: 62) 34 ----PTVPFLTPPF (SEQ ID NO: 63)

TABLE-US-00009 cluster2 HDSKLSIATQGPL (SEQ ID NO: 64) 03 HDSKLSIATQGPL (SEQ ID NO: 64) 11 -----SIATQGP- (SEQ ID NO: 65)

TABLE-US-00010 cluster3 LNLRLGQGPLFINSAHNLDINY (SEQ ID NO: 34) 02 -NLRLGQGPLF----------- (SEQ ID NO: 66) 12 ------QGPLFINSAH------ (SEQ ID NO: 67) 13 --------PLFINSAHNLD--- (SEQ ID NO: 68) 15 ----LGQGPLP----------- (SEQ ID NO: 69) 17 LNLRLGQGPL------------ (SEQ ID NO: 70) 19 -----GQGPLPI---------- (SEQ ID NO: 71) 29 -NLRLGQGPLPINS-------- (SEQ ID NO: 72) 32 ---------LFINSAHNLDINY (SEQ ID NO: 73) 33 ----------FINSAHNLDI-- (SEQ ID NO: 74) 37 --LRLGQGPLPI---------- (SEQ ID NO: 75) 39 -------GPLFINSAHN----- (SEQ ID NO: 76)

[0416] The above peptides/sequences are highly suitable as peptides for SADCs which reduce neutralization of AdV vectors.

Example 15: Epitope Mapping of Monoclonal Antibody 9C12 Against AdV

[0417] Monoclonal antibody 9C12 (alias mAB TC31-9C12.C9-s) was generated by immunizing mice with the hexon protein (Uniprot ID: P04133 which corresponds to GenBank: BAG48782.1). This neutralizing antibody is directed against the hexon protein and the neutralizing activity of this antibody was demonstrated by Varghese (Varghese et al, 2004). In brief, diluted antibody was incubated with GFP-expressing replication-defective Ad vector and subsequently added to HeLa cells followed by fluorescence readout. In order to map a region from which paratope binding peptides could be derived, the sequence at amino acid positions 1 to 952 of GenBank: BAG48782.1 was used as a starting sequence for designing cyclic 7mer, 10mer and 13mer peptides that were then synthesized and circularized on a peptide microarray, and subsequently incubated with various concentrations of the antibody. The binding signal of mAb 9C12 to the peptides yielded several candidates that could be aligned and clustered against the protein. An epitopic cluster region of 20 amino acids was identified from which paratope binding peptides can be preferentially derived. Below are the aligments of the corresponding peptide hits from this screen. The number of the peptide names corresponds to the ranked binding signal obtained from the microarray (i.e. peptide 01 binds strongest, 02 second strongest, etc.). Cyclic peptides were selected out of up to 50 top binders in this experiment.

TABLE-US-00011 cluster1 VDPMDEPTLLYVLFEVFDVV (SEQ ID NO: 35) 01 ----DEPTLLYVLFEVF--- (SEQ ID NO: 77) 02 -------TLLYVLFEVF--- (SEQ ID NO: 78) 03 ----DEPTLLYVLF------ (SEQ ID NO: 79) 04 -------TLLYVLFEVFDVV (SEQ ID NO: 80) 05 -------TLLYVLF------ (SEQ ID NO: 81) 06 ---MDEPTLLYVLFEV---- (SEQ ID NO: 82) 07 -----EPTLLYVLFE----- (SEQ ID NO: 83) 08 -DPMDEPTLLYVLF------ (SEQ ID NO: 84) 09 --------LLYVLFEVFD-- (SEQ ID NO: 85) 10 ----------YVLFEVFDVV (SEQ ID NO: 86) 11 ------PTLLYVLFEV---- (SEQ ID NO: 87) 12 ------PTLLYVLFEVFDV- (SEQ ID NO: 88) 13 ---------LYVLFEVFDV- (SEQ ID NO: 89) 14 -----EPTLLYVLFEVFD-- (SEQ ID NO: 90) 15 ---------LYVLFEV---- (SEQ ID NO: 91) 16 --PMDEPTLLYVLFE----- (SEQ ID NO: 92) 17 --------LLYVLFE----- (SEQ ID NO: 93) 18 VDPMDEPTLLYVL------- (SEQ ID NO: 94) 19 ----------YVLFEVF--- (SEQ ID NO: 95) 20 ------PTLLYVL------- (SEQ ID NO: 96)

[0418] The above peptides/sequences are highly suitable as peptides for SADCs which reduce neutralization of AdV vectors.

Example 16: Epitope Mapping of Polyclonal Antibody Ab6982 Against AdV

[0419] Polyclonal antibody ab6982 (Abcam) was generated by immunizing rabbits with purified AdV. It reacts with all capsid proteins of Ad5 including hexon, fiber and penton. It was shown that the antibody neutralizes Ad5 infection in a bioassay at 1000 adenovirus 5 particles / ml, a 50 % inactivation of the adenovirus can be achieved at a 1/25,000 dilution of the antibody. In order to identify epitopic regions that could contain peptides for ab6982 paratope binding, the antibody was mapped against the sequences of fiber (NCBI Reference Sequence: AP_000226.1) and hexon protein (GenBank: BAG48782.1). The fiber-sequence at amino acid positions 1 to 581 of (NCBI Reference Sequence: AP_000226.1), and the hexon-sequene (GenBank: BAG48782.1) at amino acid positions 1 to 952 were used as a starting sequence for designing 7mer, 10mer and 13mer cyclic peptides synthesized on a peptid array. The binding signal of this antibody to the array yielded several peptides that were aligned and clustered against the sequence of the protein. The peptide clusters were named cluster1-7 (fiber protein) and clusters8-16 (hexon protein) according to their ranked order of cyclic peptide hits (i.e. cluster contains the strongest binders, cluster2 the second strongest etc.). Below are the aligments of the corresponding peptides that bind to polyclonal antibody ab6982. The number of the peptide names corresponds to the antibody binding signal ranking from the microarray experiment, the numbers of the clusters 1-7 and clusters 8-16 are ranked by the content of top binding peptides, respectively.

TABLE-US-00012 Cluster1 MKRARPSEDTFNPVYPYD (SEQ ID NO: 36) 001 MKRARPSEDTF------- (SEQ ID NO: 97) 002 -KRARPSEDTF------- (SEQ ID NO: 98) 003 MKRARPSEDT-------- (SEQ ID NO: 99) 005 MKRARPSEDTFN------ (SEQ ID NO: 100) 010 ---ARPSEDTFNP----- (SEQ ID NO: 101) 019 --RARPSEDTFN------ (SEQ ID NO: 102) 024 ----RPSEDTF------- (SEQ ID NO: 103) 035 MKRARPSEDTFNP----- (SEQ ID NO: 104) 040 --RARPSEDTFNPVY--- (SEQ ID NO: 105) 041 ---ARPSEDT-------- (SEQ ID NO: 106) 052 -------EDTFNPVYPY- (SEQ ID NO: 107) 061 ----RPSEDTFNPVYPY- (SEQ ID NO: 108) 129 -KRARPSEDTFNPV---- (SEQ ID NO: 109) 130 --------DTFNPVY--- (SEQ ID NO: 110) 150 ----RPSEDTFNPV---- (SEQ ID NO: 111) 153 -----PSEDTFNPVY--- (SEQ ID NO: 112) 163 --------DTFNPVYPYD (SEQ ID NO: 113) Cluster2 ISGTVQSAHLIIRFD (SEQ ID NO: 37) 004 ----VQSAHLIIRF- (SEQ ID NO: 114) 006 -------AHLIIRF- (SEQ ID NO: 115) 015 -SGTVQSAHLIIRF- (SEQ ID NO: 116) 056 ---TVQSAHLIIR-- (SEQ ID NO: 117) 060 --------HLIIRFD (SEQ ID NO: 118) 065 ------SAHLIIR-- (SEQ ID NO: 119) 076 -----QSAHLIIRFD (SEQ ID NO: 120) 085 ISGTVQSAHLIIR-- (SEQ ID NO: 121) 118 --GTVQSAHLII--- (SEQ ID NO: 122) 123 --GTVQSAHLIIRFD (SEQ ID NO: 123) 126 -----QSAHLII--- (SEQ ID NO: 124) Cluster3 LGQGPLFINSAHNLDINYNKGLYLP (SEQ ID NO: 38) 009 ------------HNLDINY------ (SEQ ID NO: 125) 011 -----LFINSAHNLDINY------- (SEQ ID NO: 126) 012 ------------NLDINYNKGLYLF (SEQ ID NO: 127) 013 -------FVSPNG------------ (SEQ ID NO: 128) 016 ----------------NYINEIF-- (SEQ ID NO: 129) 020 ------------------NKGLYLF (SEQ ID NO: 130) 021 ---------------INYNKGLYLF (SEQ ID NO: 131) 023 --------NSAHNLDINY------- (SEQ ID NO: 132) 032 ------WDWSGH----NYINEIF-- (SEQ ID NO: 133) 039 ---------SGH----NYINEIF-- (SEQ ID NO: 134) 044 --LGTGLSF---------------- (SEQ ID NO: 135) 047 PFLTPPF------------------ (SEQ ID NO: 136) Cluster4 SYPFDAQNQLNLRLGQGPLFIN (SEQ ID NO: 39) 027 -------------LGQGPLF-- (SEQ ID NO: 137) 029 ----------NLRLGQGPLF-- (SEQ ID NO: 138) 030 -------NQLNLRLGQGPLF-- (SEQ ID NO: 139) 058 --------------GQGPLFI- (SEQ ID NO: 140) 059 --------QLNLRLGQGPLFI- (SEQ ID NO: 141) 062 SYPFDAQNQLNLR--------- (SEQ ID NO: 142) 066 -YPFDAQNQLNLRL-------- (SEQ ID NO: 143) 070 -----------LRLGQGPLFI- (SEQ ID NO: 144) 072 -------NQLNLRL-------- (SEQ ID NO: 145) 073 ---FDAQNQLNLR--------- (SEQ ID NO: 146) 082 ------QNQLNLR--------- (SEQ ID NO: 147) 093 ---------------QGPLFIN (SEQ ID NO: 148) 102 --PFDAQNQLNLRLG------- (SEQ ID NO: 149) 112 ----DAQNQLNLRL-------- (SEQ ID NO: 150) 117 ------------RLGQGPLFIN (SEQ ID NO: 151) 136 --------QLNLRLG------- (SEQ ID NO: 152) 147 ---FDAQNQLNLRLGQ------ (SEQ ID NO: 153) 148 ---------LNLRLGQGPLPIN (SEQ ID NO: 154) 169 -----AQNQLNLRLG------- (SEQ ID NO: 155) 172 -----AQNQLNL---------- (SEQ ID NO: 156) 173 ---------LNLRLGQ------ (SEQ ID NO: 157) 178 SYPFDAQNQL------------ (SEQ ID NO: 158) 197 --PFDAQNQLNL---------- (SEQ ID NO: 159) Cluster5 GDTTPSAYSMSFSWDWGHNYIN (SEQ ID NO: 40) 008 ---------YSMSFSW------- (SEQ ID NO: 160) 014 ----TPSAYSMSFSWDW------ (SEQ ID NO: 161) 022 ----------MSFSWDW------ (SEQ ID NO: 162) 028 -----PSAYSMSFSW-------- (SEQ ID NO: 163) 049 --DTTPSAYSMSFSW-------- (SEQ ID NO: 164) 078 ---TTPSAYSMSF---------- (SEQ ID NO: 165) 079 --------YSMSFSWDWS----- (SEQ ID NO: 166) 091 TGDTTPSAYSMSF---------- (SEQ ID NO: 167) 095 ------------FSWDWSGHNY- (SEQ ID NO: 168) 100 ----------SFSWDWS----- (SEQ ID NO: 169) 108 -----SAYSMSF---------- (SEQ ID NO: 170) 134 ----------SFSWDWSGHN-- (SEQ ID NO: 171) 143 -----SAYSMSFSWD------- (SEQ ID NO: 172) 144 --------SMSFSWD------- (SEQ ID NO: 173) 149 ------------SWDWSGHNYI (SEQ ID NO: 174) 167 ------AYSMSFS--------- (SEQ ID NO: 175) 176 --------SMSFSWDWSGHNY- (SEQ ID NO: 176) 186 -----------FSWDWSG---- (SEQ ID NO: 177) 193 ------------SWDWSGH--- (SEQ ID NO: 178) Cluster6 VLLNNSFLDPEYWNFRN (SEQ ID NO: 41) 017 ------FLDPEYWNFR- (SEQ ID NO: 179) 018 -----SFLDPEYWNF-- (SEQ ID NO: 180) 031 ---------PEYWNFR- (SEQ ID NO: 181) 033 --LNNSFLDPEYWNF-- (SEQ ID NO: 182) 034 ---NNSFLDPEYWNFR- (SEQ ID NO: 183) 050 ------FLDPEYW---- (SEQ ID NO: 184) 053 --------DPEYWNF-- (SEQ ID NO: 185) 068 ---NNSFLDPEYW---- (SEQ ID NO: 186) 088 VLLNNSFLDPEYW---- (SEQ ID NO: 187) 113 ----------EYWNFRN (SEQ ID NO: 188) 114 --LNNSFLDPEY----- (SEQ ID NO: 189) 155 -------LDPEYWNFRN (SEQ ID NO: 190) 180 --LNNSFLD-------- (SEQ ID NO: 191) 187 ----NSFLDPEYWN--- (SEQ ID NO: 192) Cluster7 HNYINEIFATSSYTFSYIA (SEQ ID NO: 42) 042 ----------SSYTFSY-- (SEQ ID NO: 193) 043 -------FATSSYTFSY-- (SEQ ID NO: 194) 055 --YINEIFATSSYTF---- (SEQ ID NO: 195) 064 -----------SYTFSYI- (SEQ ID NO: 196) 080 --------ATSSYTF---- (SEQ ID NO: 197) 089 -----EIFATSSYTF---- (SEQ ID NO: 198) 092 ----NEIFATSSYTFSY-- (SEQ ID NO: 199) 097 --------ATSSYTFSYI- (SEQ ID NO: 200) 099 HNYINEIFATSSY------ (SEQ ID NO: 201) 104 ------IFATSSY------ (SEQ ID NO: 202) 110 ---INEIFATSSY------ (SEQ ID NO: 203) 119 -NYINEIFATSSYT----- (SEQ ID NO: 204) 168 --YINEIFA---------- (SEQ ID NO: 205) 181 ------------YTFSYIA (SEQ ID NO: 206) 200 -----EIFATSSYTFSYI- (SEQ ID NO: 207) Cluster8 DEAATALEINLEEEDDDNEDEVDEQAEQQKTH (SEQ ID NO: 43) 01 -----ALEINLEEEDDDN-------------- (SEQ ID NO: 208) 02 ---ATALEINLEEEDD---------------- (SEQ ID NO: 209) 03 -EAATALEINLEEE------------------ (SEQ ID NO: 210) 04 ------LEINLEE------------------- (SEQ ID NO: 211) 05 ----TALEINLEEEDDD--------------- (SEQ ID NO: 212) 06 -------EINLEEE------------------ (SEQ ID NO: 213) 07 -----ALEINLEEED----------------- (SEQ ID NO: 214) 08 ------LEINLEEEDD---------------- (SEQ ID NO: 215) 09 ----TALEINLEEE------------------ (SEQ ID NO: 216) 11 DEAATALEINLEE------------------- (SEQ ID NO: 217) 13 ------LEINLEEEDDDNE------------- (SEQ ID NO: 218) 14 --AATALEINLEEED----------------- (SEQ ID NO: 219) 15 -------EINLEEEDDD--------------- (SEQ ID NO: 220) 19 ---ATALEINLEE------------------- (SEQ ID NO: 221) 23 --------INLEEEDDDN-------------- (SEQ ID NO: 222) 27 ---------NLEEEDDDNE------------- (SEQ ID NO: 223) 10 -------------------DEVDEQA------ (SEQ ID NO: 224) 12 -------------EDDDNEDEVDEQA------ (SEQ ID NO: 225) 16 ---------------DDNEDEVDEQAEQ---- (SEQ ID NO: 226) 17 --------------------EVDEQAE----- (SEQ ID NO: 227) 18 ----------------DNEDEVDEQA------ (SEQ ID NO: 228) 20 ---------------------VDEQAEQ---- (SEQ ID NO: 229) 21 ------------------EDEVDEQAEQQKT- (SEQ ID NO: 230) 22 ------------------EDEVDEQAEQ---- (SEQ ID NO: 231) 24 -------------------DEVDEQAEQQKTH (SEQ ID NO: 232) 25 -----------------NEDEVDEQAEQQK-- (SEQ ID NO: 233) 26 -------------------DEVDEQAEQQ--- (SEQ ID NO: 234) Cluster9 INLEEEDDDNEDEVDEQAEQ (SEQ ID NO: 44) 028 EINLEEEDDDNED------- (SEQ ID NO: 235) 029 --NLEEEDDDNEDEV----- (SEQ ID NO: 236) 032 -INLEEED------------ (SEQ ID NO: 237) 034 ---LEEEDDDNED------- (SEQ ID NO: 238) 035 -INLEEEDDDNEDE------ (SEQ ID NO: 239) 037 -------DDDNEDEVDEQAE (SEQ ID NO: 240) 053 ---LEEEDDDNEDEVD---- (SEQ ID NO: 241) 057 --------DDNEDEVDEQ-- (SEQ ID NO: 242) 063 ------EDDDNED------- (SEQ ID NO: 243) 065 --NLEEEDD----------- (SEQ ID NO: 244) 078 --------DDNEDEV----- (SEQ ID NO: 245) 087 -------DDDNEDEVDE--- (SEQ ID NO: 246) 096 -------DDDNEDE------ (SEQ ID NO: 247) 097 ----EEEDDDNEDE------ (SEQ ID NO: 248) 108 -----EEDDDNE--------- (SEQ ID NO: 249) 121 ------EDDDNEDEVD----- (SEQ ID NO: 250) 126 -----------EDEVDEQ--- (SEQ ID NO: 251) 148 -----EEDDDNEDEVDEQ--- (SEQ ID NO: 252) 185 -----EEDDDNEDEV------ (SEQ ID NO: 253) 188 ----EEEDDDNEDEVDE---- (SEQ ID NO: 254) Cluster10 DNEDEVDEQAEQQKTHVF (SEQ ID NO: 45) 030 ----EVDEQAEQQK---- (SEQ ID NO: 255) 031 DNEDEVDEQAEQQ----- (SEQ ID NO: 256) 036 -----VDEQAEQQKT--- (SEQ ID NO: 257) 038 ----EVDEQAEQQKTHV- (SEQ ID NO: 258) 041 -----VDEQAEQQKTHVF (SEQ ID NO: 259) Cluster11 EWDEAATALEINLEE (SEQ ID NO: 46) 033 --------ALEINLE (SEQ ID NO: 260) 042 --WDEAATALEINLE (SEQ ID NO: 261) 043 -----AATALEINLE (SEQ ID NO: 262) 112 ENDEAATALEINL-- (SEQ ID NO: 263) 124 ---EAATALEINL-- (SEQ ID NO: 264) Cluster12 PKVVLYSEDVDIETPDTHISYMP (SEQ ID NO: 47) 039 ----LYSEDVDIET--------- (SEQ ID NO: 265) 040 ----LYSEDVDIETPDT------ (SEQ ID NO: 266) 044 -KVVLYSEDVDIET--------- (SEQ ID NO: 267) 045 -----------IETPDTH----- (SEQ ID NO: 268) 046 ---------VDIETPDTHI---- (SEQ ID NO: 269) 047 ---VLYSEDVDIE---------- (SEQ ID NO: 270) 048 --------DVDIETPDTHISY-- (SEQ ID NO: 271) 049 --VVLYSEDVDIETP-------- (SEQ ID NO: 272) 050 ------SEDVDIETPDTHI---- (SEQ ID NO: 273) 051 ------------ETPDTHI---- (SEQ ID NO: 274) 052 ---VLYSEDVDIETPD------- (SEQ ID NO: 275) 054 --------DVDIETPDTH----- (SEQ ID NO: 276) 055 ----------DIETPDTHIS--- (SEQ ID NO: 277) 056 -------EDVDIETPDTHIS--- (SEQ ID NO: 278) 058 -----------IETPDTHISY-- (SEQ ID NO: 279) 059 -----YSEDVDIETPDTH----- (SEQ ID NO: 280) 060 ---------VDIETPDTHISYM- (SEQ ID NO: 281) 061 PKVVLYSEDVDIE---------- (SEQ ID NO: 282) 062 ----------DIETPDT------ (SEQ ID NO: 283) 064 ----------DIETPDTHISYMP (SEQ ID NO: 284) 070 -------EDVDIETPDT------ (SEQ ID NO: 285) 071 ------------ETPDTHISYM- (SEQ ID NO: 286) 159 -----------IETPDTHISYMP (SEQ ID NO: 287) Cluster13 YIPESYKDRMYSFFRNF (SEQ ID NO: 48) 072 -------DRMYSFFRNF (SEQ ID NO: 288) 086 -------DRMYSFF--- (SEQ ID NO: 289) 104 ----------YSFFRNF (SEQ ID NO: 290) 107 -IPESYKDRMYSFF--- (SEQ ID NO: 291) 120 ----SYKDRMYSFF--- (SEQ ID NO: 292) 127 ---ESYKDRMYSF---- (SEQ ID NO: 293) 143 ------KDRMYSF---- (SEQ ID NO: 294) 152 YIPESYKDRMYSF---- (SEQ ID NO: 295) 153 --PESYKDRMYSFFR-- (SEQ ID NO: 296) 160 -----YKDRMYSFFR-- (SEQ ID NO: 297) Cluster14 DSIGDRTRYFSMW (SEQ ID NO: 49) 073 ------TRYFSMW (SEQ ID NO: 298) 080 ---GDRTRYF--- (SEQ ID NO: 299) 095 DSIGDRTRYF--- (SEQ ID NO: 300) 100 DSIGDRTRYFSMW (SEQ ID NO: 301) 101 ---GDRTRYFSMW (SEQ ID NO: 302) Cluster15 SYKDRMYSFFRNF (SEQ ID NO: 50) 072 ---DRMYSFFRNF (SEQ ID NO: 303) 099 SYKDRMYSFFRNF (SEQ ID NO: 304) Cluster16 FLVQMLANYNIGYQGFY (SEQ ID NO: 51) 106 -------NYNIGYQGFY (SEQ ID NO: 305) 122 ------ANYNIGYQGF- (SEQ ID NO: 306) 123 ----MLANYNIGYQGFY (SEQ ID NO: 307) 136 ----------IGYQGFY (SEQ ID NO: 308) 184 FLVQMLANYNIGY---- (SEQ ID NO: 309) 187 ---------NIGYQGF- (SEQ ID NO: 310) 190 ---QMLANYNIGYQGF- (SEQ ID NO: 311)

[0420] The above peptides/sequences are highly suitable as peptides for SADCs which reduce neutralization of AdV vectors. Importantly, binding of these peptides to the paratope of unwanted antibodies can be even further improved by mutating 1, 2 or 3 amino acids in order to generate mimotopes with improved antibody binding properties.

Example 17: Epitope Mapping of mAb ADK8 Against AAV

[0421] Monoclonal antibody ADK8 was generated by immunizing mice with AAV8 capsids. It is directed against the assembled AAV8 capsid (Sonntag et al, 2011). The neutralizing function of the antibody was previously demonstrated (Gurda et al, 2012). In brief, AAV8 was pre-incubated with ADK8 which lead to a decline in the number of virus particles present in the cytoplasm. Moreover, the binding of AAV8 to the nuclear membrane as well as the nuclear entry were abrogated following neutralization by ADK8. This suggests that ADK8 neutralization might interfere either with the cellular entry and / or the transport to the nucleus. ADK8 also cross-reacts with capsid proteins from other AAV serotypes such as AAV1, AAV3, AAV7 (Mietzsch et al, 2014) and was therefore chosen as an example from which general conclusions about the present invention can be drawn.

[0422] As for the other antibodies (see examples above), several clusters were identified, delineating regions from which preferred peptides can be deduced. Most preferably, the peptides aligned below according to their binding strengths can be used for selective antibody depletion and detection as hereinabove.

TABLE-US-00013 Cluster1 WQNRDVYLQGPIWAKIP (SEQ ID NO: 52) 01 ------YLQGPIW---- (SEQ ID NO: 312) 02 -----VYLQGPI----- (SEQ ID NO: 313) 03 WQNRDVY---------- (SEQ ID NO: 314) 05 ----DVYLQGP------ (SEQ ID NO: 315) 08 -QNRDVYL--------- (SEQ ID NO: 316) 12 -------LQGPIWA--- (SEQ ID NO: 317) 20 ---RDVYLQG------- (SEQ ID NO: 318) 50 --NRDVYLQ-------- (SEQ ID NO: 319) Cluster2 DNTYFGYSTPWGYFDFNRFHC (SEQ ID NO: 53) 07 ---YFGYSTPWGYFDF----- (SEQ ID NO: 320) 09 ----FGYSTPWGYF------- (SEQ ID NO: 321) 10 -----GYSTPWGYFD------ (SEQ ID NO: 322) 11 ------YSTPWGYFDF----- (SEQ ID NO: 323) 17 -NTYFGYSTPWGYF------- (SEQ ID NO: 324) 18 --------TPWGYFDFNRFHC (SEQ ID NO: 325) 23 --TYFGYSTPWGYFD------ (SEQ ID NO: 326) 26 DNTYFGYSTPWGY-------- (SEQ ID NO: 327) 28 ---YFGYSTPWGY-------- (SEQ ID NO: 328) 34 ----FGYSTPWGYFDFN---- (SEQ ID NO: 329) Cluster3 MANQAKNWLPGPCY (SEQ ID NO: 54) 04 ------NWLPGPC- (SEQ ID NO: 330) 15 -------WLPGPCY (SEQ ID NO: 331) 16 ---QAKNWLPGPC- (SEQ ID NO: 332) 21 ----AKNWLPGPCY (SEQ ID NO: 333) 25 MANQAKNWLPGPC- (SEQ ID NO: 334) Cluster4 LPYVLGSAHQGCLPPFP (SEQ ID NO: 55) 06 ---------QGCLPPF- (SEQ ID NO: 335) 13 ----------GCLPPFP (SEQ ID NO: 336) 27 ---VLGSAHQGCLPPF- (SEQ ID NO: 337) 32 LPYVLGSAHQGCL---- (SEQ ID NO: 338) 37 -YVLGSAHQGC------ (SEQ ID NO: 339) 38 ----------CLPPFPA (SEQ ID NO: 340) 39 -----SAHQGCLPPF-- (SEQ ID NO: 341) 45 --VLGSAHQGCL----- (SEQ ID NO: 342) 46 PYVLGSAHQGCLP---- (SEQ ID NO: 343) Cluster5 NGSQAVGRSSFYCLEYF (SEQ ID NO: 56) 14 ------GRSSFYC---- (SEQ ID NO: 344) 22 ----AVGRSSFYCLEYF (SEQ ID NO: 345) 24 ----AVGRSSFYCL--- (SEQ ID NO: 346) 33 ---QAVGRSSFYCLEY- (SEQ ID NO: 347) 35 NGSQAVGRSSFYC---- (SEQ ID NO: 348) Cluster6 PLIDQYLYYL (SEQ ID NO: 57) 19 ---DQYLYYL (SEQ ID NO: 349) 29 PLIDQYLYYL (SEQ ID NO: 350) 36 --IDQYLYY- (SEQ ID NO: 351) Cluster7 EERFFPSNGILIF (SEQ ID NO: 58) 31 ---FFPSNGILIF (SEQ ID NO: 352) 49 EERFFPSNGILIF (SEQ ID NO: 353) Cluster8 ADGVGSSSGNWHC (SEQ ID NO: 59) 42 ---VGSSSGNWHC (SEQ ID NO: 354) 48 ADGVGSSSGNWHC (SEQ ID NO: 355)

Example 18: Screen for Anti-AAV Antibodies in Human Sera

[0423] 2452 linear peptides derived from the sequences of 16 different AAVs used in gene therapy and with a sequence length of 15 amino-acids each were synthesized.

[0424] Samples obtained from human donors were screened for antibodies against these AAV-derived peptides immobilized on microarrays. To this end, IgG was prepared from blood obtained from the human donors by protein G purification. Each IgG sample was incubated with the peptide microarrays and Ig binding signals were detected by fluorescence. All antibody binding signals to the peptides on the arrays were background subtracted and ranked for each sample and a deduplicated aggregate of the respective top 250 peptide hits for each donor with the corresponding protein sequence of origin (as obtained from UniProt or other sources) was compiled (designated as group IV). Further, the deduplicated aggregate of the respective top 50 peptide hits for each donor was compiled and designated as group III. Further, the deduplicated aggregate of the respective top 25 peptide hits for each donor was compiled and designated as group II. Finally, the deduplicated aggregate of the respective top 10 peptide hits for each donor was compiled and designated as group I.

[0425] Detailed results are shown in Table 1 below. Altogether, group I contains 110 distinct peptide hits (assigned to the corresponding AAV vectors in Table 1), group II contains 289 distinct peptide hits, group III contains 428 distinct peptide hits and group IV contains 1271 distinct peptide hits. Evidently, group I is a subset of group II which in turn is a subset of group III which in turn is a subset of group IV. Groups I-IV correspond to the top 4.4%, 10.5%, 17.5% and 51.8%, respectively, of all peptides screened.

[0426] Thus, all listed peptides, preferably peptides belonging to group III, even more preferably belonging to group II and most preferably belonging to group I (i.e. to the top 4.4%), provide sequences from which shorter peptide sequences can be derived for antibody depletion according to the present invention. Furthermore, also other peptide sequences (or fragments) from the proteins from which the peptides of Table 1 were derived (preferably from group III, more preferably however from group II, most preferably from group I), are suited to be used for SADCs according to the present invention. In addition, these peptides can also be used as probes for the diagnostic detection of anti-AAV antibodies in biological samples such as human sera.

Table 1

[0427] This table lists the detailed results of a screen for linear peptides as a basis for the construction of anti-AAV antibody depleting SADCs according to the present invention. These peptides are also suitable typing neutralizing antibodies directed against AAV gene therapy vectors. If not stated otherwise, the peptides represent fragments from different AAV VP1 proteins. Source given is either UniProt ID, GenBank ID, PDB ID or AAV strain name.

TABLE-US-00014 peptide # SEQ ID NO peptide group I group II group III group IV source 1 383 LRTGNNFEFSYQFED X X X X AA088201.1 2 384 TGNNFEFSYQFEDVP X X X X AA088201.1 3 385 VATEQYGWADNLQQ X X X X AA088201.1 4 386 FEFSYFEDVPFHSSY X X X X AAV-Rh74 c 5 387 RTGNFEFSYFEDVPF X X X X AAV-Rh74 c 6 388 MLRTGNFEFSYFEDV X X X X AAV-Rh74 c 7 389 PVPADPPTTFNQAKL X X X X AAV-Rh74 c 8 390 TQSTGGTAGTQQLLF X X X X AAV-Rh74 c 9 391 EEEIKTTNPVATEQY X X X X AAV-Rh74 c 10 392 SSVMLTSEEEIKTTN X X X X AAV-Rh74 c 11 393 VDFAVNTEGTYSEPR X X X X AAV-Rh74 c 12 394 SVPDPQPIGEPPAGP X X X X AAV-Rh74 c 13 395 EEIKTTNPVATEQYG X X X X AAV-Rh74 c 14 396 PIGEPPAGPSGLGSG X X X X AAV-Rh74 c 15 397 VNTEGTYSEPRPIGT X X X X AAV-Rh74 c 16 398 YSSVMLTSEEEIKTT X X X X AAV-Rh74 c 17 399 VATNHQSAQTLAVPF X X X X ALU85156.1 18 400 VSTNLQRGNLALGET X X X X AOD99651.1 19 401 ALGETTRPATAAQTQ X X X X AOD99656.1 20 402 TQTTGGTTNTQTLGF X X X X pdb3J1QA 21 403 DDEEKFFPQSGVLIF X X X X P03135 22 404 EEEIRTTNPVATEQY X X X X P03135 23 405 PVEPDSSSGTGKAGQ X X X X P03135 24 406 IQYTSNYNKSVNVDF X X X X P03135 25 407 TDEEEIRTTNPVATE X X X X P03135 26 408 VDFTVDTNGVYSEPR X X X X P03135 27 409 VDTNGVYSEPRPIGT X X X X P03135 28 410 TMATGSGAPMADNNE X X X X P03135 29 411 TSTVQVFTDSEYQLP X X X X P03135 30 412 LYYLSRTNTPSGTTT X X X X P03135 31 413 TADVNTQGVLPGMVW X X X X P03135 32 414 GSEKTNVDIEKVMIT X X X X P03135 33 415 TNTMATGSGAPMADN X X X X P03135 34 416 WNPEIQYTSNYNKSV X X X X P03135 35 417 SYTFEDVPFHSSYAH X X X X O56137 36 418 EDVPFHSSYAHSQSL X X X X O56137 37 419 SSTDPATGDVHVMGA X X X X O56137 38 420 ATERFGTVAVNLQSS X X X X O56137 39 421 WLEDNLSEGIREWWD X X X X O56137 40 422 EEEIKATNPVATERF X X X X O56137 41 423 LEDNLSEGIREWWDL X X X X O56137 42 424 DAEFQERLQEDTSFG X X X X O56137 43 425 EWELQKENSKRWNPE X X X X O56137 44 426 SFITQYSTGQVSVEI X X X X O56137 45 427 EIEWELQKENSKRWN X X X X O56137 46 428 ITQYSTGQVSVEIEW X X X X O56137 47 429 TDEEEIKATNPVATE X X X X O56137 48 430 EEGAKTAPGKKRPVE X X X X O56137 49 431 IQVKEVTTNDGVTTI X X X X O56137 50 432 SDSEYQLPYVLGSAH X X X X O56137 51 433 PLGEPPATPAAVGPT X X X X O56137 52 434 SSASTGASNDNHYFG X X X X O56137 53 435 PVDQSPQEPDSSSGV X X X X O56139 54 436 EEAAKTAPGKKRPVD X X X X O56139 55 437 APGKKRPVDQSPQEP X X X X O56139 56 438 ILEPLGLVEEAAKTA X X X X O56139 57 439 TRTVNDQGALPGMVW X X X X O56139 58 440 KRPVDQSPQEPDSSS X X X X O56139 59 441 PLGEPPAAPTSLGSN X X X X O56139 60 442 GKKRPVDQSPQEPDS X X X X O56139 61 443 KTAPGKKRPVDQSPQ X X X X O56139 62 444 SNAELDNVMITDEEE X X X X O56139 63 445 WLEDNLSEGIREWWA X X X X Q6JC40 64 446 PVPADPPTAFNKDKL X X X X Q6JC40 65 447 EFENVPFHSSYAHSQ X X X X Q6JC40 66 448 FQERLKEDTSFGGNL X X X X Q6JC40 67 449 PQILIKNTPVPADPP X X X X Q6JC40 68 450 ADAEFQERLKEDTSF X X X X Q6JC40 69 451 EEIKTTNPVATESYG X X X X Q6JC40 70 452 VEFAVNTEGVYSEPR X X X X Q6JC40 71 453 AEFQERLKEDTSFGG X X X X Q6JC40 72 454 EPDSSAGIGKSGAQP X X X X Q6JC40 73 455 LIKNTPVPADPPTAF X X X X Q6JC40 74 456 VMITNEEEIKTTNPV X X X X Q6JC40 75 457 VNTEGVYSEPRPIGT X X X X Q6JC40 76 458 DKLNSFITQYSTGQV X X X X Q6JC40 77 459 VATESYGQVATNHQS X X X X Q6JC40 78 460 DDEERFFPSNGILIF X X X X Q8JQF8 79 461 EEEIKTTNPVATEEY X X X X Q8JQF8 80 462 PVPADPPTTFNQSKL X X X X Q8JQF8 81 463 LIKNTPVPADPPTTF X X X X Q8JQF8 82 464 SSSGNWHCDSTWLGD X X X X Q8JQF8 83 465 TSVDFAVNTEGVYSE X X X X Q8JQF8 84 466 TTTGQNNNSNFAWTA X X X X Q8JQF8 85 467 VDFAVNTEGVYSEPR X X X X Q8JQF8 86 468 VSTTTGQNNNSNFAW X X X X Q8JQF8 87 469 KTAPGKKRPVEPSPQ X X X X Q8JQF8 88 470 TQTTGGTANTQTLGF X X X X Q8JQF8 89 471 VLEPLGLVEEGAKTA X X X X Q8JQF8 90 472 EEVGEGLREFLGLEA X X X X Q9YIJ1 91 473 DAEFQEKLADDTSFG X X X X Q9YIJ1 92 474 SFVDHPPDWLEEVGE X X X X Q9YIJ1 93 475 EWELKKENSKRWNPE X X X X Q9YIJ1 94 476 EMEWELKKENSKRWN X X X X Q9YIJ1 95 477 TNNYNDPQFVDFAPD X X X X Q9YIJ1 96 478 FEEVPFHSSFAPSQN X X X X Q9YIJ1 97 479 QYTNNYNDPQFVDFA X X X X Q9YIJ1 98 480 TSTVQVFTDDDYQLP X X X X Q9YIJ1 99 481 EDSKPSTSSDAEAGP X X X X Q9YIJ1 100 482 EEGAKTAPTGKRIDD X X X X Q9YIJ1 101 483 EVPFHSSFAPSQNLF X X X X Q9YIJ1 102 484 SSFITQYSTGQVTVE X X X X Q9YIJ1 103 485 ELEGASYQVPPQPNG X X X X Q9YIJ1 104 486 ERDVYLQGPIWAKIP X X X X Q9YIJ1 105 487 PQYGYATLNRDNTEN X X X X Q9YIJ1 106 488 QVTVEMEWELKKENS X X X X Q9YIJ1 107 489 VTVQDSTTTIANNLT X X X X Q9YIJ1 108 490 YNEQLEAGDNPYLKY X X X X Q9YIJ1 109 491 YNNHQYREIKSGSVD X X X X Q9YIJ1 110 492 TSSDAEAGPSGSQQL X X X X Q9YIJ1 111 493 FEFSYQFEDVPFHSS X X X AA088201.1 112 494 NNFEFSYQFEDVPFH X X X AA088201.1 113 495 YQFEDVPFHSSYAHS X X X AA088201.1 114 496 QGAGKDNVDYSSVML X X X AA088201.1 115 497 TPVPADPPTTFSQAK X X X AA088201.1 116 498 IKTTNPVATEQYGW X X X AA088201.1 117 499 GNFEFSYFEDVPFHS X X X AAV-Rh74 c 118 500 FSYFEDVPFHSSYAH X X X AAV-Rh74 c 119 501 YFEDVPFHSSYAHSQ X X X AAV-Rh74 c 120 502 EYFPSQMLRTGNFEF X X X AAV-Rh74 c 121 503 EIKTTNPVATEQYGW X X X AAV-Rh74 c 122 504 RTQSTGGTAGTQQLL X X X AAV-Rh74 c 123 505 DNVDYSSVMLTSEEE X X X AAV-Rh74 c 124 506 DEERFFPSSGVLMFG X X X AAV-Rh74 c 125 507 TNVDFAVNTEGTYSE X X X AAV-Rh74 c 126 508 EIQYTSNYYKSTNVD X X X AAV-Rh74 c 127 509 RVSTTLSQNNNSNFA X X X AAV-Rh74 c 128 510 SESVPDPQPIGEPPA X X X AAV-Rh74 c 129 511 QRVSTTLSQNNNSNF X X X AAV-Rh74 c 130 512 VDYSSVMLTSEEEIK X X X AAV-Rh74 c 131 513 PQPIGEPPAGPSGLG X X X AAV-Rh74 c 132 514 QQRVSTTLSQNNNSN X X X AAV-Rh74 c 133 515 VSTTLSQNNNSNFAW X X X AAV-Rh74 c 134 516 TTRPATAPQIGTVNS X X X AOD99652.1 135 517 EYGAVAINNQAANLA X X X AOD99654.1 136 518 TTRPATAAQTQWNN X X X AOD99656.1 137 519 NQSLALGETTRPAST X X X AOD99659.1 138 520 GQMATNNQSLALGET X X X AOD99659.1 139 521 MATNNQSLALGETTR X X X AOD99659.1 140 522 TNNQSLALGETTRPA X X X AOD99659.1 141 523 DSVPDPQPIGEPPAA X X X pdb3J1QA 142 524 TGDADSVPDPQPIGE X X X pdb3J1QA 143 525 SLTMAAGGGAPMADN X X X pdb3J1QA 144 526 TTGGTTNTQTLGFSQ X X X pdb3J1QA 145 527 LYYLSRTQTTGGTTN X X X pdb3J1QA 146 528 SRTQTTGGTTNTQTL X X X pdb3J1QA 147 529 YLSRTQTTGGTTNTQ X X X pdb3J1QA 148 530 DGYLPDWLEDTLSEG X X X P03135 149 531 PPFPADVFMVPQYGY X X X P03135 150 532 GEPVNEADAAALEHD X X X P03135 151 533 VNVDFTVDTNGVYSE X X X P03135 152 534 EEKFFPQSGVLIFGK X X X P03135 153 535 PDWLEDTLSEGIRQW X X X P03135 154 536 PVNEADAAALEHDKA X X X P03135 155 537 TNVDIEKVMITDEEE X X X P03135 156 538 VDIEKVMITDEEEIR X X X P03135 157 539 PEIQYTSNYNKSVNV X X X P03135 158 540 VEEPVKTAPGKKRPV X X X P03135 159 541 ASHKDDEEKFFPQSG X X X P03135 160 542 EPVNEADAAALEHDK X X X P03135 161 543 ERHKDDSRGLVLPGY X X X P03135 162 544 GNSSGNWHCDSTWMG X X X P03135 163 545 PVPANPSTTFSAAKF X X X P03135 164 546 AAALEHDKAYDRQLD X X X P03135 165 547 FNGLDKGEPVNEADA X X X P03135 166 548 YTSNYNKSVNVDFTV X X X P03135 167 549 EDTLSEGIRQWWKLK X X X P03135 168 550 EPDSSSGTGKAGQQP X X X P03135 169 551 NNSEYSWTGATKYHL X X X P03135 170 552 SNYNKSVNVDFTVDT X X X P03135 171 553 SSQSGASNDNHYFGY X X X P03135 172 554 KRWNPEIQYTSNYNK X X X P03135 173 555 YLSRTNTPSGTTTQS X X X P03135 174 556 YTFEDVPFHSSYAHS X X X O56137 175 557 FEDVPFHSSYAHSQS X X X O56137 176 558 QSSSTDPATGDVHVM X X X O56137 177 559 PDWLEDNLSEGIREW X X X O56137 178 560 DWLEDNLSEGIREWW X X X O56137 179 561 QYSTGQVSVEIEWEL X X X O56137 180 562 DGYLPDWLEDNLSEG X X X O56137 181 563 EDNLSEGIREWWDLK X X X O56137 182 564 DNHYFGYSTPWGYFD X X X O56137 183 565 PVEQSPQEPDSSSGI X X X O56137 184 566 ADGYLPDWLEDNLSE X X X O56137 185 567 GDSESVPDPQPLGEP X X X O56137 186 568 GEPVNAADAAALEHD X X X O56137 187 569 EDTSFGGNLGRAVFQ X X X O56137 188 570 GCLPPFPADVFMIPQ X X X O56137 189 571 PVPANPPAEFSATKF X X X O56137 190 572 SESVPDPQPLGEPPA X X X O56137 191 573 EFQERLQEDTSFGGN X X X O56137 192 574 DAAALEHDKAYDQQL X X X O56137 193 575 EPVNAADAAALEHDK X X X O56137 194 576 QRVSKTKTDNNNSNF X X X O56137 195 577 DSESVPDPQPLGEPP X X X O56137 196 578 EHDKAYDQQLKAGDN X X X O56137 197 579 LPGMVWQDRDVYLQG X X X O56137 198 580 VSVEIEWELQKENSK X X X O56137 199 581 DSEYQLPYVLGSAHQ X X X O56137 200 582 PQPLGEPPATPAAVG X X X O56137 201 583 VEIEWELQKENSKRW X X X O56137 202 584 EYFPSQMLRTGNNFT X X X O56137 203 585 PLIDQYLYYLNRTQN X X X O56137 204 586 QVSVEIEWELQKENS X X X O56137 205 587 ASNDNHYFGYSTPWG X X X O56137 206 588 EIKATNPVATERFGT X X X O56137 207 589 GSAHQGCLPPFPADV X X X O56137 208 590 SSSGIGKTGQQPAKK X X X O56137 209 591 AAALEHDKAYDQQLK X X X O56137 210 592 NNFQFSYTFEDVPFH X X X O56139 211 593 TGNNFQFSYTFEDVP X X X O56139 212 594 LRTGNNFQFSYTFED X X X O56139 213 595 EADAAALEHDKAYDQ X X X O56139 214 596 PQPLGEPPAAPTSLG X X X O56139 215 597 SSSGVGKSGKQPARK X X X O56139 216 598 DDEEKFFPMHGNLIF X X X O56139 217 599 QRLSKTANDNNNSNF X X X O56139 218 600 TTSGTTNQSRLLFSQ X X X O56139 219 601 SYEFENVPFHSSYAH X X X Q6JC40 220 602 QFSYEFENVPFHSSY X X X Q6JC40 221 603 ERLKEDTSFGGNLGR X X X Q6JC40 222 604 ESVPDPQPIGEPPAA X X X Q6JC40 223 605 NNVEFAVNTEGVYSE X X X Q6JC40 224 606 NEEEIKTTNPVATES X X X Q6JC40 225 607 SLIFGKQGTGRDNVD X X X Q6JC40 226 608 EDNLSEGIREWWALK X X X Q6JC40 227 609 NSFITQYSTGQVSVE X X X Q6JC40 228 610 SSNDNAYFGYSTPWG X X X Q6JC40 229 611 TPVPADPPTAFNKDK X X X Q6JC40 230 612 VEEAAKTAPGKKRPV X X X Q6JC40 231 613 IKNTPVPADPPTAFN X X X Q6JC40 232 614 IKTTNPVATESYGQV X X X Q6JC40 233 615 IQYTSNYYKSNNVEF X X X Q6JC40 234 616 QILIKNTPVPADPPT X X X Q6JC40 235 617 AFNKDKLNSFITQYS X X X Q6JC40 236 618 EYFPSQMLRTGNNFQ X X X Q6JC40 237 619 ITNEEEIKTTNPVAT X X X Q6JC40 238 620 LKEDTSFGGNLGRAV X X X Q6JC40 239 621 VATNHQSAQAQAQTG X X X Q6JC40 240 622 DADKVMITNEEEIKT X X X Q6JC40 241 623 SLTMASGGGAPVADN X X X Q6JC40 242 624 NKDKLNSFITQYSTG X X X Q6JC40 243 625 QPIGEPPAAPSGVGS X X X Q6JC40 244 626 DNADYSDVMLTSEEE X X X Q8JQF8 245 627 TYTFEDVPFHSSYAH X X X Q8JQF8 246 628 ARDNADYSDVMLTSE X X X Q8JQF8 247 629 IGTVNSQGALPGMVW X X X Q8JQF8 248 630 EEYGIVADNLQQQNT X X X Q8JQF8 249 631 QRVSTTTGQNNNSNF X X X Q8JQF8 250 632 DGVGSSSGNWHCDST X X X Q8JQF8 251 633 IKNTPVPADPPTTFN X X X Q8JQF8 252 634 ILIKNTPVPADPPTT X X X Q8JQF8 253 635 STIQVFTDSEYQLPY X X X Q8JQF8 254 636 CYRQQRVSTTTGQNN X X X Q8JQF8 255 637 HDKAYDQQLQAGDNP X X X Q8JQF8 256 638 LYYLSRTQTTGGTAN X X X Q8JQF8 257 639 TFNQSKLNSFITQYS X X X Q8JQF8 258 640 VTQNEGTKTIANNLT X X X Q8JQF8 259 641 QYLYYLSRTQTTGGT X X X Q8JQF8 260 642 SRTQTTGGTANTQTL X X X Q8JQF8 261 643 NTYFGYSTPWGYFDF X X X Q8JQF8 262 644 PVEPSPQRSPDSSTG X X X Q8JQF8 263 645 SVPDPQPLGEPPAAP X X X Q8JQF8 264 646 EPSPQRSPDSSTGIG X X X Q8JQF8 265 647 NNFEFTYNFEEVPFH X X X Q9YIJ1 266 648 PDWLEEVGEGLREFL X X X Q9YIJ1 267 649 TGNNFEFTYNFEEVP X X X Q9YIJ1 268 650 LRTGNNFEFTYNFEE X X X Q9YIJ1 269 651 EPVNRADEVAREHDI X X X Q9YIJ1 270 652 TEEDSKPSTSSDAEA X X X Q9YIJ1 271 653 TQYSTGQVTVEMEWE X X X Q9YIJ1 272 654 ESETQPVNRVAYNVG X X X Q9YIJ1 273 655 NLTSTVQVFTDDDYQ X X X Q9YIJ1 274 656 EIQYTNNYNDPQFVD X X X Q9YIJ1 275 657 PVPGNITSFSDVPVS X X X Q9YIJ1 276 658 TVEMEWELKKENSKR X X X Q9YIJ1 277 659 EFQEKLADDTSFGGN X X X Q9YIJ1 278 660 EQLEAGDNPYLKYNH X X X Q9YIJ1 279 661 NYNDPQFVDFAPDST X X X Q9YIJ1 280 662 SSLGADTMSAGGGGP X X X Q9YIJ1 281 663 SKPSTSSDAEAGPSG X X X Q9YIJ1 282 664 FITQYSTGQVTVEME X X X Q9YIJ1 283 665 EFLGLEAGPPKPKPN X X X Q9YIJ1 284 666 NVGGQMATNNQSSTT X X X Q9YIJ1 285 667 PSKMLRTGNNFEFTY X X X Q9YIJ1 286 668 VLEPFGLVEEGAKTA X X X Q9YIJ1 287 669 AQPASSLGADTMSAG X X X Q9YIJ1 288 670 VQDSTTTIANNLTST X X X Q9YIJ1 289 671 YLEGNMLITSESETQ X X X Q9YIJ1 290 672 NVDFAVNTDGTYSEP X X AAO88201.1 291 673 KDNVDYSSVMLTSEE X X AAO88201.1 292 674 HDDEERFFPSSGVLM X X AAV-Rh74 c 293 675 SQMLRTGNFEFSYFE X X AAV-Rh74 c 294 676 GDSESVPDPQPIGEP X X AAV-Rh74 c 295 677 DNPYLRYHADAEFQE X X AAV-Rh74 c 296 678 NTPVPADPPTTFNQA X X AAV-Rh74 c 297 679 DSLVNPGVAMATHDD X X AAV-Rh74 c 298 680 PLGLVESPVKTAPGK X X AAV-Rh74 c 299 681 SRTQSTGGTAGTQQL X X AAV-Rh74 c 300 682 TFNQAKLASFITQYS X X AAV-Rh74 c 301 683 STTLSQNNNSNFAWT X X AAV-Rh74 c 302 684 SSTGIGKKGQQPAKK X X AAV-Rh74 c 303 685 KSTNVDFAVNTEGTY X X AAV-Rh74 c 304 686 TYSEPRPIGTRYLTR X X AAV-Rh74 c 305 687 EYGIVADNLQQQNLA X X AOD99652.1 306 688 RPATAPQIGTVNSQG X X AOD99652.1 307 689 GETTRPATAAQTQVV X X AOD99656.1 308 690 EYGIVSSNLQAANLA X X AOD99656.1 309 691 SNLQAANLALGETTR X X AOD99656.1 310 692 DADSVPDPQPIGEPP X X pdb3J1QA 311 693 QGVLPGMVWQDRDVY X X P03135 312 694 NEADAAALEHDKAYD X X P03135 313 695 QGCLPPFPADVFMVP X X P03135 314 696 EHDKAYDRQLDSGDN X X P03135 315 697 PFPADVFMVPQYGYL X X P03135 316 698 EPVKTAPGKKRPVEH X X P03135 317 699 HKDDEEKFFPQSGVL X X P03135 318 700 DKGEPVNEADAAALE X X P03135 319 701 EQYGSVSTNLQRGNR X X P03135 320 702 GPPPPKPAERHKDDS X X P03135 321 703 IEKVMITDEEEIRTT X X P03135 322 704 KSVNVDFTVDTNGVY X X P03135 323 705 RPVEHSPVEPDSSSG X X P03135 324 706 SDIRDQSRNWLPGPC X X P03135 325 707 DNNEGADGVGNSSGN X X P03135 326 708 PVATEQYGSVSTNLQ X X P03135 327 709 QVKEVTQNDGTTTIA X X P03135 328 710 STVQVFTDSEYQLPY X X P03135 329 711 DADSVPDPQPLGQPP X X P03135 330 712 DSGDNPYLKYNHADA X X P03135 331 713 DSLVNPGPAMASHKD X X P03135 332 714 ISSQSGASNDNHYFG X X P03135 333 715 MITDEEEIRTTNPVA X X P03135 334 716 RQWWKLKPGPPPPKP X X P03135 335 717 VKEVTQNDGTTTIAN X X P03135 336 718 VTQNDGTTTIANNLT X X P03135 337 719 ADNNEGADGVGNSSG X X P03135 338 720 PLGLVEEPVKTAPGK X X P03135 339 721 GNNFTFSYTFEDVPF X X O56137 340 722 FSYTFEDVPFHSSYA X X O56137 341 723 TFSYTFEDVPFHSSY X X O56137 342 724 DDKDKFFPMSGVMIF X X O56137 343 725 TFEDVPFHSSYAHSQ X X O56137 344 726 TGDVHVMGALPGMVW X X O56137 345 727 HVMGALPGMVWQDRD X X O56137 346 728 TVAVNLQSSSTDPAT X X O56137 347 729 AVNLQSSSTDPATGD X X O56137 348 730 NHYFGYSTPWGYFDF X X O56137 349 731 GSQAVGRSSFYCLEY X X O56137 350 732 TQYSTGQVSVEIEWE X X O56137 351 733 YLPDWLEDNLSEGIR X X O56137 352 734 SNTALDNVMITDEEE X X O56137 353 735 TPWGYFDFNRFHCHF X X O56137 354 736 YFDFNRFHCHFSPRD X X O56137 355 737 GYLPDWLEDNLSEGI X X O56137 356 738 YSTGQVSVEIEWELQ X X O56137 357 739 SLDRLMNPLIDQYLY X X O56137 358 740 STVQVFSDSEYQLPY X X O56137 359 741 SVPDPQPLGEPPATP X X O56137 360 742 EFSATKFASFITQYS X X O56137 361 743 YSTPWGYFDFNRFHC X X O56137 362 744 AHQGCLPPFPADVFM X X O56137 363 745 ASFITQYSTGQVSVE X X O56137 364 746 EWWDLKPGAPKPKAN X X O56137 365 747 GEPPATPAAVGPTTM X X O56137 366 748 MVWQDRDVYLQGPIW X X O56137 367 749 DKGEPVNAADAAALE X X O56137 368 750 ERLQEDTSFGGNLGR X X O56137 369 751 EYQLPYVLGSAHQGC X X O56137 370 752 FITQYSTGQVSVEIE X X O56137 371 753 MITDEEEIKATNPVA X X O56137 372 754 AADAAALEHDKAYDQ X X O56137 373 755 AVGPTTMASGGGAPM X X O56137 374 756 DSTWLGDRVITTSTR X X O56137 375 757 ATPAAVGPTTMASGG X X O56137 376 758 DNNEGADGVGNASGN X X O56137 377 759 EQSPQEPDSSSGIGK X X O56137 378 760 FNIQVKEVTTNDGVT X X O56137 379 761 PAAVGPTTMASGGGA X X O56137 380 762 SSYAHSQSLDRLMNP X X O56137 381 763 TAPGKKRPVEQSPQE X X O56137 382 764 FHSSYAHSQSLDRLM X X O56137 383 765 FNGLDKGEPVNAADA X X O56137 384 766 HSSYAHSQSLDRLMN X X O56137 385 767 TTSTRTWALPTYNNH X X O56137 386 768 VKEVTTNDGVTTIAN X X O56137 387 769 DGVGNSSGNWHCDSQ X X O56139 388 770 NSSGNWHCDSQWLGD X X O56139 389 771 AKKRILEPLGLVEEA X X O56139 390 772 PVPANPPTTFSPAKF X X O56139 391 773 NNSNFPWTAASKYHL X X O56139 392 774 PDSSSGVGKSGKQPA X X O56139 393 775 QSSNTAPTTRTVNDQ X X O56139 394 776 TVANNLQSSNTAPTT X X O56139 395 777 AELDNVMITDEEEIR X X O56139 396 778 EEKFFPMHGNLIFGK X X O56139 397 779 GNNFQFSYEFENVPF X X Q6JC40 398 780 NVEFAVNTEGVYSEP X X Q6JC40 399 781 MLRTGNNFQFSYEFE X X Q6JC40 400 782 RTGNNFQFSYEFENV X X Q6JC40 401 783 STVQVFTDSDYQLPY X X Q6JC40 402 784 DGSQAVGRSSFYCLE X X Q6JC40 403 785 EFAVNTEGVYSEPRP X X Q6JC40 404 786 EFAWPGASSWALNGR X X Q6JC40 405 787 DTESVPDPQPIGEPP X X Q6JC40 406 788 NNNSEFAWPGASSWA X X Q6JC40 407 789 NTPVPADPPTAFNKD X X Q6JC40 408 790 STTVTQNNNSEFAWP X X Q6JC40 409 791 EIQYTSNYYKSNNVE X X Q6JC40 410 792 ENVPFHSSYAHSQSL X X Q6JC40 411 793 ILIKNTPVPADPPTA X X Q6JC40 412 794 RVSTTVRQNNNSEFA X X Q6JC40 413 795 SDYQLPYVLGSAHEG X X Q6JC40 414 796 GNGLDKGEPVNAADA X X Q6JC40 415 797 KSNNVEFAVNTEGVY X X Q6JC40 416 798 LNSFITQYSTGQVSV X X Q6JC40 417 799 QQTLKFSVAGPSNMA X X Q6JC40 418 800 SSGNWHCDSQWLGDR X X Q6JC40 419 801 ADNNEGADGVGSSSG X X Q6JC40 420 802 ASGGGAPVADNNEGA X X Q6JC40 421 803 IGEPPAAPSGVGSLT X X Q6JC40 422 804 PLGLVEEAAKTAPGK X X Q6JC40 423 805 SAGIGKSGAQPAKKR X X Q6JC40 424 806 ENSKRWNPEIQYTSN X X Q6JC40 425 807 ELQKENSKRWNPEIQ X X Q6JC40 426 808 GNNFQFTYTFEDVPF X X Q8JQF8 427 809 EERFFPSNGILIFGK X X Q8JQF8 428 810 PVATEEYGIVADNLQ X X Q8JQF8 429 811 QFTYRFEDVPFHSSY X X Q8JQF8 430 812 NTPVPADPPTTFNQS X X Q8JQF8 431 813 EIKTTNPVATEEYGI X X Q8JQF8 432 814 GSSSGNWHCDSTWLG X X Q8JQF8 433 815 RTGNNFQFTYTFEDV X X Q8JQF8 434 816 TNPVATEEYGIVADN X X Q8JQF8 435 817 TSEEEIKTTNPVATE X X Q8JQF8 436 818 GPCYRQQRVSTTTGQ X X Q8JQF8 437 819 LPGPCYRQQRVSTTT X X Q8JQF8 438 820 TTGGTANTQTLGFSQ X X Q8JQF8 439 821 KQISNGTSGGATNDN X X Q8JQF8 440 822 KQNAARDNADYSDVM X X Q8JQF8 441 823 NAARDNADYSDVMLT X X Q8JQF8 442 824 SKLNSFITQYSTGQV X X Q8JQF8 443 825 VKEVTQNEGTKTIAN X X Q8JQF8 444 826 VNSQGALPGMVWQNR X X Q8JQF8 445 827 NNSNFAWTAGTKYHL X X Q8JQF8 446 828 QQQNTAPQIGTVNSQ X X Q8JQF8 447 829 YNNHLYKQISNGTSG X X Q8JQF8 448 830 YSDVMLTSEEEIKTT X X Q8JQF8 449 831 DNTYFGYSTPWGYFD X X Q8JQF8 450 832 TYFGYSTPWGYFDFN X X Q8JQF8 451 833 ESVPDPQPLGEPPAA X X Q8JQF8 452 834 STGIGKKGQQPARKR X X Q8JQF8 453 835 FGYSTPWGYFDFNRF X X Q9YIJ1 454 836 YFGYSTPWGYFDFNR X X Q9YIJ1 455 837 NAYFGYSTPWGYFDF X X Q9YIJ1 456 838 HPPDWLEEVGEGLRE X X Q9YIJ1 457 839 TENPTERSSFFCLEY X X Q9YIJ1 458 840 WLEEVGEGLREFLGL X X Q9YIJ1 459 841 YSTGQVTVEMEWELK X X Q9YIJ1 460 842 FVDFAPDSTGEYRTT X X Q9YIJ1 461 843 QEIVPGSVWMERDVY X X Q9YIJ1 462 844 TPWGYFDFNRFHSHW X X Q9YIJ1 463 845 ANAYFGYSTPWGYFD X X Q9YIJ1 464 846 DDDYQLPYVVGNGTE X X Q9YIJ1 465 847 DEVAREHDISYNEQL X X Q9YIJ1 466 848 ELKKENSKRWNPEIQ X X Q9YIJ1 467 849 GNASGDWHCDSTWMG X X Q9YIJ1 468 850 GYNYLGPGNGLDRGE X X Q9YIJ1 469 851 TSFSDVPVSSFITQY X X Q9YIJ1 470 852 ANNLTSTVQVFTDDD X X Q9YIJ1 471 853 DQYLYRFVSTNNTGG X X Q9YIJ1 472 854 EYRTTRPIGTRYLTR X X Q9YIJ1 473 855 IFNIQVKEVTVQDST X X Q9YIJ1 474 856 ENSKRWNPEIQYTNN X X Q9YIJ1 475 857 AGPPKPKPNQQHQDQ X X Q9YIJ1 476 858 PSTSSDAEAGPSGSQ X X Q9YIJ1 477 859 TGQVTVEMEWELKKE X X Q9YIJ1 478 860 VKIFNIQVKEVTVQD X X Q9YIJ1 479 861 DSTTTIANNLTSTVQ X X Q9YIJ1 480 862 ISYNEQLEAGDNPYL X X Q9YIJ1 481 863 LGLEAGPPKPKPNQQ X X Q9YIJ1 482 864 TAPATGTYNLQEIVP X X Q9YIJ1 483 865 TMSAGGGGPLGDNNQ X X Q9YIJ1 484 866 FSYQFEDVPFHSSYA X AAO88201.1 485 867 VLMFGKQGAGKDNVD X AAO88201.1 486 868 DFAVNTDGTYSEPRP X AAO88201.1 487 869 DGTYSEPRPIGTRYL X AAO88201.1 488 870 GAVNSQGALPGMVWQ X AAO88201.1 489 871 QMLRTGNNFEFSYQF X AAO88201.1 490 872 MFGKQGAGKDNVDYS X AAO88201.1 491 873 APIVGAVNSQGALPG X AAO88201.1 492 874 IVGAVNSQGALPGMV X AAO88201.1 493 875 LQQQNAAPIVGAVNS X AAO88201.1 494 876 NTDGTYSEPRPIGTR X AAO88201.1 495 877 STNVDFAVNTDGTYS X AAO88201.1 496 878 KDDEERFFPSSGVLM X AAO88201.1 497 879 THKDDEERFFPSSGV X AAO88201.1 498 880 VNPGVAMATHKDDEE X AAO88201.1 499 881 KNTPVPADPPTTFSQ X AAO88201.1 500 882 MATHKDDEERFFPSS X AAO88201.1 501 883 NPVATEQYGVVADNL X AAO88201.1 502 884 PGVAMATHKDDEERF X AAO88201.1 503 885 RDSLVNPGVAMATHK X AAO88201.1 504 886 TTNPVATEQYGVVAD X AAO88201.1 505 887 VPADPPTTFSQAKLA X AAO88201.1 506 888 YFPSQMLRTGNNFEF X AAO88201.1 507 889 PSQMLRTGNNFEFSY X AAO88201.1 508 890 VLMFGKQGAGDNVDY X AAV-Rh74 c 509 891 AGDNPYLRYHADAEF X AAV-Rh74 c 510 892 AGDNVDYSSVMLTSE X AAV-Rh74 c 511 893 FPSQMLRTGNFEFSY X AAV-Rh74 c 512 894 IVGAVSQGALPGMVW X AAV-Rh74 c 513 895 NWGFRPKRLNFLFNI X AAV-Rh74 c 514 896 PVATEQYGWADNLQQ X AAV-Rh74 c 515 897 EQYGWADNLQQQNAA X AAV-Rh74 c 516 898 GPFNGLDKGEPVAAD X AAV-Rh74 c 517 899 LVNPGVAMATHDDEE X AAV-Rh74 c 518 900 LYYLSRTQSTGGTAG X AAV-Rh74 c 519 901 NNMSAQAKNWLPGPC X AAV-Rh74 c 520 902 YLGPFNGLDKGEPVA X AAV-Rh74 c 521 903 ATEQYGWADNLQQQN X AAV-Rh74 c 522 904 ATHDDEERFFPSSGV X AAV-Rh74 c 523 905 CLEYFPSQMLRTGNF X AAV-Rh74 c 524 906 DKGEPVAADAAALEH X AAV-Rh74 c 525 907 FLFNIQVKEVTQNEG X AAV-Rh74 c 526 908 GEPVAADAAALEHDK X AAV-Rh74 c 527 909 LRYHADAEFQERLQE X AAV-Rh74 c 528 910 NPGVAMATHDDEERF X AAV-Rh74 c 529 911 PVAADAAALEHDKAY X AAV-Rh74 c 530 912 QTGDSESVPDPQPIG X AAV-Rh74 c 531 913 YHADAEFQERLQEDT X AAV-Rh74 c 532 914 DPPTTFNQAKLASFI X AAV-Rh74 c 533 915 GFRPKRLNFLFNIQV X AAV-Rh74 c 534 916 GPNNMSAQAKNWLPG X AAV-Rh74 c 535 917 GVAMATHDDEERFFP X AAV-Rh74 c 536 918 KTTNPVATEQYGWAD X AAV-Rh74 c 537 919 LEPLGLVESPVKTAP X AAV-Rh74 c 538 920 LNFLFNIQVKEVTQN X AAV-Rh74 c 539 921 NNNWGFRPKRLNFLF X AAV-Rh74 c 540 922 PSSGVLMFGKQGAGD X AAV-Rh74 c 541 923 PYLRYHADAEFQERL X AAV-Rh74 c 542 924 RVLEPLGLVESPVKT X AAV-Rh74 c 543 925 SPVKTAPGKKRPVEP X AAV-Rh74 c 544 926 SQAGPNNMSAQAKNW X AAV-Rh74 c 545 927 STGGTAGTQQLLFSQ X AAV-Rh74 c 546 928 TGGTAGTQQLLFSQA X AAV-Rh74 c 547 929 TNPVATEQYGWADNL X AAV-Rh74 c 548 930 VESPVKTAPGKKRPV X AAV-Rh74 c 549 931 VKTAPGKKRPVEPSP X AAV-Rh74 c 550 932 VSQGALPGMVWQNRD X AAV-Rh74 c 551 933 YLSRTQSTGGTAGTQ X AAV-Rh74 c 552 934 YYLSRTQ$TGGTAGT X AAV-Rh74 c 553 935 NMSAQAKNWLPGPCY X AAV-Rh74 c 554 936 GEPPAGPSGLGSGTM X AAV-Rh74 c 555 937 SEEEIKTTNPVATEQ X AAV-Rh74 c 556 938 NVDYSSVMLTSEEEI X AAV-Rh74 c 557 939 FAVNTEGTYSEPRPI X AAV-Rh74 c 558 940 SNYYKSTNVDFAVNT X AAV-Rh74 c 559 941 TEGTYSEPRPIGTRY X AAV-Rh74 c 560 942 ERFFPSSGVLMFGKQ X AAV-Rh74 c 561 943 HLYKQISNGTSGGST X AAV-Rh74 c 562 944 IGKKGQQPAKKRLNF X AAV-Rh74 c 563 945 MSAQAKNWLPGPCYR X AAV-Rh74 c 564 946 PDPQPIGEPPAGPSG X AAV-Rh74 c 565 947 QYLYYLSRTQ$TGGT X AAV-Rh74 c 566 948 SVMLTSEEEIKTTNP X AAV-Rh74 c 567 949 TLSQNNNSNFAWTGA X AAV-Rh74 c 568 950 YYKSTNVDFAVNTEG X AAV-Rh74 c 569 951 AGPSGLGSGTMAAGG X AAV-Rh74 c 570 952 AQAKNWLPGPCYRQQ X AAV-Rh74 c 571 953 CYRQQRVSTTLSQNN X AAV-Rh74 c 572 954 DQYLYYLSRTQSTGG X AAV-Rh74 c 573 955 DYSSVMLTSEEEIKT X AAV-Rh74 c 574 956 GLGSGTMAAGGGAPM X AAV-Rh74 c 575 957 GRDSLVNPGVAMATH X AAV-Rh74 c 576 958 IDQYLYYLSRTQSTG X AAV-Rh74 c 577 959 IQYTSNYYKSTNVDF X AAV-Rh74 c 578 960 KKGQQPAKKRLNFGQ X AAV-Rh74 c 579 961 KLASFITQYSTGQVS X AAV-Rh74 c 580 962 KYHLNGRDSLVNPGV X AAV-Rh74 c 581 963 LNGRDSLVNPGVAMA X AAV-Rh74 c 582 964 NPEIQYTSNYYKSTN X AAV-Rh74 c 583 965 PEIQYTSNYYKSTNV X AAV-Rh74 c 584 966 PLIDQYLYYLSRTQS X AAV-Rh74 c 585 967 QAKLASFITQYSTGQ X AAV-Rh74 c 586 968 QISNGTSGGSTNDNT X AAV-Rh74 c 587 969 QYTSNYYKSTNVDFA X AAV-Rh74 c 588 970 RQQRVSTTLSQNNNS X AAV-Rh74 c 589 971 SNGTSGGSTNDNTYF X AAV-Rh74 c 590 972 SQNNNSNFAWTGATK X AAV-Rh74 c 591 973 TGIGKKGQQPAKKRL X AAV-Rh74 c 592 974 TSNYYKSTNVDFAVN X AAV-Rh74 c 593 975 TTLSQNNNSNFAWTG X AAV-Rh74 c 594 976 YKQISNGTSGGSTND X AAV-Rh74 c 595 977 YRQQRVSTTLSQNNN X AAV-Rh74 c 596 978 NNSNFAWTGATKYHL X AAV-Rh74 c 597 979 GSTNDNTYFGYSTPW X AAV-Rh74 c 598 980 DNGRGLVLPGYKYLG X AAV-Rh74 c 599 981 NNNSNFAWTGATKYH X AAV-Rh74 c 600 982 PKPKANQQKQDNGRG X AAV-Rh74 c 601 983 QQKQDNGRGLVLPGY X AAV-Rh74 c 602 984 SNFAWTGATKYHLNG X AAV-Rh74 c 603 985 LAVPFKAQAQTGWVQ X ALU85156.1 604 986 QTLAVPFKAQAQTGW X ALU85156.1 605 987 SRTINGSGQNQQTLK X ALU85156.1 606 988 GETTRPARQAATADV X AOD99651.1 607 989 ALGETTRPARQAATA X AOD99651.1 608 990 GSVSTNLQRGNLALG X AOD99651.1 609 991 QYGSVSTNLQRGNLA X AOD99651.1 610 992 RPARQAATADVNTQG X AOD99651.1 611 993 TTRPARQAATADVNT X AOD99651.1 612 994 DNLQQQNLALGETTR X AOD99652.1 613 995 GETTRPATAPQIGTV X AOD99652.1 614 996 GIVADNLQQQNLALG X AOD99652.1 615 997 VADNLQQQNLALGET X AOD99652.1 616 998 RPATQAQTGLVHNQG X AOD99654.1 617 999 VADNLQQLALGETTR X AOD99655.1 618 1000 GETTRPAANTGPIVG X AOD99655.1 619 1001 RPAANTGPIVGNVNS X AOD99655.1 620 1002 TEQYGWADNLQQLA X AOD99655.1 621 1003 TTRPAANTGPIVGNV X AOD99655.1 622 1004 VSSNLQAANLALGET X AOD99656.1 623 1005 GIVSSNLQAANLALG X AOD99656.1 624 1006 RPATAAQTQVVNNQG X AOD99656.1 625 1007 GETTRPASTTAPATG X AOD99659.1 626 1008 SLALGETTRPASTTA X AOD99659.1 627 1009 TTRPASTTAPATGTY X AOD99659.1 628 1010 VGGQMATNNQSLALG X AOD99659.1 629 1011 EAAKTAPGKKRPVEH X pdb3J1QA 630 1012 APSGVGSLTMAAGGG X pdb3J1QA 631 1013 GGTTNTQTLGFSQGG X pdb3J1QA 632 1014 VGSLTMAAGGGAPMA X pdb3J1QA 633 1015 GADGVGNSSGNWHCD X P03135 634 1016 ADAAALEHDKAYDRQ X P03135 635 1017 CLPPFPADVFMVPQY X P03135 636 1018 DKAYDRQLDSGDNPY X P03135 637 1019 EGADGVGNSSGNWHC X P03135 638 1020 NNEGADGVGNSSGNW X P03135 639 1021 YLPDWLEDTLSEGIR X P03135 640 1022 ALEHDKAYDRQLDSG X P03135 641 1023 DVNTQGVLPGMVWQD X P03135 642 1024 GPAMASHKDDEEKFF X P03135 643 1025 LPPFPADVFMVPQYG X P03135 644 1026 QRVSKTSADNNNSEY X P03135 645 1027 AADGYLPDWLEDTLS X P03135 646 1028 SSGNWHCDSTWMGDR X P03135 647 1029 FPADVFMVPQYGYLT X P03135 648 1030 GPFNGLDKGEPVNEA X P03135 649 1031 GVGNSSGNWHCDSTW X P03135 650 1032 NNLTSTVQVFTDSEY X P03135 651 1033 NPGPAMASHKDDEEK X P03135 652 1034 TAPGKKRPVEHSPVE X P03135 653 1035 VLPGMVWQDRDVYLQ X P03135 654 1036 VSKTSADNNNSEYSW X P03135 655 1037 AMASHKDDEEKFFPQ X P03135 656 1038 ATEQYGSVSTNLQRG X P03135 657 1039 DNNNSEYSWTGATKY X P03135 658 1040 DSVPDPQPLGQPPAA X P03135 659 1041 EKTNVDIEKVMITDE X P03135 660 1042 EVTQNDGTTTIANNL X P03135 661 1043 GNWHCDSTWMGDRVI X P03135 662 1044 KKRPVEHSPVEPDSS X P03135 663 1045 KPGPPPPKPAERHKD X P03135 664 1046 KTSADNNNSEYSWTG X P03135 665 1047 NEGADGVGNSSGNWH X P03135 666 1048 NLTSTVQVFTDSEYQ X P03135 667 1049 NTQGVLPGMVWQDRD X P03135 668 1050 RLNFGQTGDADSVPD X P03135 669 1051 SRLQFSQAGASDIRD X P03135 670 1052 TVQVFTDSEYQLPYV X P03135 671 1053 VQVFTDSEYQLPYVL X P03135 672 1054 WLEDTLSEGIRQWWK X P03135 673 1055 YNKSVNVDFTVDTNG X P03135 674 1056 ADGVGNSSGNWHCDS X P03135 675 1057 ADVFMVPQYGYLTLN X P03135 676 1058 ANNLTSTVQVFTDSE X P03135 677 1059 APSGLGTNTMATGSG X P03135 678 1060 FKLFNIQVKEVTQND X P03135 679 1061 GCLPPFPADVFMVPQ X P03135 680 1062 GIRQWWKLKPGPPPP X P03135 681 1063 GLDKGEPVNEADAAA X P03135 682 1064 KKRVLEPLGLVEEPV X P03135 683 1065 KQGSEKTNVDIEKVM X P03135 684 1066 KVMITDEEEIRTTNP X P03135 685 1067 LTSTVQVFTDSEYQL X P03135 686 1068 MADNNEGADGVGNSS X P03135 687 1069 PARKRLNFGQTGDAD X P03135 688 1070 PPPKPAERHKDDSRG X P03135 689 1071 SADNNNSEYSWTGAT X P03135 690 1072 TLSEGIRQWWKLKPG X P03135 691 1073 TNGVYSEPRPIGTRY X P03135 692 1074 TNTPSGTTTQSRLQF X P03135 693 1075 WMGDRVITTSTRTWA X P03135 694 1076 AATADVNTQGVLPGM X P03135 695 1077 AYDRQLDSGDNPYLK X P03135 696 1078 CDSTWMGDRVITTST X P03135 697 1079 DDSRGLVLPGYKYLG X P03135 698 1080 DPQPLGQPPAAPSGL X P03135 699 1081 EIRTTNPVATEQYGS X P03135 700 1082 FGKQGSEKTNVDIEK X P03135 701 1083 FTVDTNGVYSEPRPI X P03135 702 1084 GASDIRDQSRNWLPG X P03135 703 1085 GLVEEPVKTAPGKKR X P03135 704 1086 GNRQAATADVNTQGV X P03135 705 1087 GQTGDADSVPDPQPL X P03135 706 1088 GRDSLVNPGPAMASH X P03135 707 1089 GSGAPMADNNEGADG X P03135 708 1090 GVLIFGKQGSEKTNV X P03135 709 1091 HSPVEPDSSSGTGKA X P03135 710 1092 IQVKEVTQNDGTTTI X P03135 711 1093 IRDQSRNWLPGPCYR X P03135 712 1094 KEVTQNDGTTTIANN X P03135 713 1095 KGEPVNEADAAALEH X P03135 714 1096 KLFNIQVKEVTQNDG X P03135 715 1097 KLKPGPPPPKPAERH X P03135 716 1098 LEPLGLVEEPVKTAP X P03135 717 1099 LIFGKQGSEKTNVDI X P03135 718 1100 LNFKLFNIQVKEVTQ X P03135 719 1101 NFGQTGDADSVPDPQ X P03135 720 1102 NLQRGNRQAATADVN X P03135 721 1103 NTPVPANPSTTFSAA X P03135 722 1104 PAAPSGLGTNTMATG X P03135 723 1105 PAERHKDDSRGLVLP X P03135 724 1106 PGKKRPVEHSPVEPD X P03135 725 1107 PLIDQYLYYLSRTNT X P03135 726 1108 PMADNNEGADGVGNS X P03135 727 1109 PQILIKNTPVPANPS X P03135 728 1110 QAGASDIRDQSRNWL X P03135 729 1111 QISSQSGASNDNHYF X P03135 730 1112 QRGNRQAATADVNTQ X P03135 731 1113 QSGVLIFGKQGSEKT X P03135 732 1114 RKRLNFGQTGDADSV X P03135 733 1115 RQQRVSKTSADNNNS X P03135 734 1116 RTTNPVATEQYGSVS X P03135 735 1117 RVLEPLGLVEEPVKT X P03135 736 1118 SAAKFASFITQYSTG X P03135 737 1119 SEYSWTGATKYHLNG X P03135 738 1120 SGTTTQSRLQFSQAG X P03135 739 1121 SRGLVLPGYKYLGPF X P03135 740 1122 SSGTGKAGQQPARKR X P03135 741 1123 TFSAAKFASFITQYS X P03135 742 1124 TGDADSVPDPQPLGQ X P03135 743 1125 TNPVATEQYGSVSTN X P03135 744 1126 VFMVPQYGYLTLNNG X P03135 745 1127 VNEADAAALEHDKAY X P03135 746 1128 VPDPQPLGQPPAAPS X P03135 747 1129 WWKLKPGPPPPKPAE X P03135 748 1130 GATKYHLNGRDSLVN X P03135 749 1131 NFTFSYTFEDVPFHS X O56137 750 1132 RTGNNFTFSYTFEDV X O56137 751 1133 EPFGLVEEGAKTAPG X O56137 752 1134 PVATERFGTVAVNLQ X O56137 753 1135 DVHVMGALPGMVWQD X O56137 754 1136 ERFGTVAVNLQSSST X O56137 755 1137 MGGFGLKHPPPQILI X O56137 756 1138 AMASHKDDKDKFFPM X O56137 757 1139 DVPFHSSYAHSQSLD X O56137 758 1140 FGTVAVNLQSSSTDP X O56137 759 1141 FHPSPLMGGFGLKHP X O56137 760 1142 GLKHPPPQILIKNTP X O56137 761 1143 GRAVFQAKKRVLEPF X O56137 762 1144 HPSPLMGGFGLKHPP X O56137 763 1145 KDKFFPMSGVMIFGK X O56137 764 1146 KHPPPQILIKNTPVP X O56137 765 1147 LMGGFGLKHPPPQIL X O56137 766 1148 NLQSSSTDPATGDVH X O56137 767 1149 PSPLMGGFGLKHPPP X O56137 768 1150 TDPATGDVHVMGALP X O56137 769 1151 LPPFPADVFMIPQYG X O56137 770 1152 FDFNRFHCHFSPRDW X O56137 771 1153 PPFPADVFMIPQYGY X O56137 772 1154 HYFGYSTPWGYFDFN X O56137 773 1155 CLPPFPADVFMIPQY X O56137 774 1156 NNLTSTVQVFSDSEY X O56137 775 1157 SQAVGRSSFYCLEYF X O56137 776 1158 DNLSEGIREWWDLKP X O56137 777 1159 LDRLMNPLIDQYLYY X O56137 778 1160 PFPADVFMIPQYGYL X O56137 779 1161 QAVGRSSFYCLEYFP X O56137 780 1162 QGCLPPFPADVFMIP X O56137 781 1163 GADGVGNASGNWHCD X O56137 782 1164 NLSEGIREWWDLKPG X O56137 783 1165 RSSFYCLEYFPSQML X O56137 784 1166 TDGHFHPSPLMGGFG X O56137 785 1167 VDFTVDNNGLYTEPR X O56137 786 1168 AADGYLPDWLEDNLS X O56137 787 1169 ANVDFTVDNNGLYTE X O56137 788 1170 FPADVFMIPQYGYLT X O56137 789 1171 LPDWLEDNLSEGIRE X O56137 790 1172 MAADGYLPDWLEDNL X O56137 791 1173 SNDNHYFGYSTPWGY X O56137 792 1174 VLPGYKYLGPFNGLD X O56137 793 1175 WGYFDFNRFHCHFSP X O56137 794 1176 EVTTNDGVTTIANNL X O56137 795 1177 GNWHCDSTWLGDRVI X O56137 796 1178 NDNHYFGYSTPWGYF X O56137 797 1179 PAEFSATKFASFITQ X O56137 798 1180 PYLRYNHADAEFQER X O56137 799 1181 YNHADAEFQERLQED X O56137 800 1182 DFNRFHCHFSPRDWQ X O56137 801 1183 DNPYLRYNHADAEFQ X O56137 802 1184 DRLMNPLIDQYLYYL X O56137 803 1185 GRSSFYCLEYFPSQM X O56137 804 1186 HQGCLPPFPADVFMI X O56137 805 1187 MGALPGMVWQDRDVY X O56137 806 1188 PHTDGHFHPSPLMGG X O56137 807 1189 QTGDSESVPDPQPLG X O56137 808 1190 SVEIEWELQKENSKR X O56137 809 1191 VGRSSFYCLEYFPSQ X O56137 810 1192 VQVFSDSEYQLPYVL X O56137 811 1193 YKYLGPFNGLDKGEP X O56137 812 1194 DGVGNASGNWHCDST X O56137 813 1195 GDNPYLRYNHADAEF X O56137 814 1196 GGGAPMADNNEGADG X O56137 815 1197 GQVSVEIEWELQKEN X O56137 816 1198 KGEPVNAADAAALEH X O56137 817 1199 LGPFNGLDKGEPVNA X O56137 818 1200 LTSTVQVFSDSEYQL X O56137 819 1201 NASGNWHCDSTWLGD X O56137 820 1202 NNGLYTEPRPIGTRY X O56137 821 1203 PDPQPLGEPPATPAA X O56137 822 1204 QSLDRLMNPLIDQYL X O56137 823 1205 SQSLDRLMNPLIDQY X O56137 824 1206 VEEGAKTAPGKKRPV X O56137 825 1207 ADAEFQERLQEDTSF X O56137 826 1208 ADVFMIPQYGYLTLN X O56137 827 1209 GMVWQDRDVYLQGPI X O56137 828 1210 IDQYLYYLNRTQNQS X O56137 829 1211 KLFNIQVKEVTTNDG X O56137 830 1212 KRPVEQSPQEPDSSS X O56137 831 1213 KTKTDNNNSNFTWTG X O56137 832 1214 KYLGPFNGLDKGEPV X O56137 833 1215 NAADAAALEHDKAYD X O56137 834 1216 NTPVPANPPAEFSAT X O56137 835 1217 PVNAADAAALEHDKA X O56137 836 1218 PWGYFDFNRFHCHFS X O56137 837 1219 QEDTSFGGNLGRAVF X O56137 838 1220 SAHQGCLPPFPADVF X O56137 839 1221 SGGGAPMADNNEGAD X O56137 840 1222 TGQVSVEIEWELQKE X O56137 841 1223 VFSDSEYQLPYVLGS X O56137 842 1224 VSKTKTDNNNSNFTW X O56137 843 1225 VWQDRDVYLQGPIWA X O56137 844 1226 YLGPFNGLDKGEPVN X O56137 845 1227 AALEHDKAYDQQLKA X O56137 846 1228 ADAAALEHDKAYDQQ X O56137 847 1229 AEFQERLQEDTSFGG X O56137 848 1230 AVGRSSFYCLEYFPS X O56137 849 1231 DDGRGLVLPGYKYLG X O56137 850 1232 DNNNSNFTWTGASKY X O56137 851 1233 ESIINPGTAMASHKD X O56137 852 1234 FGQTGDSESVPDPQP X O56137 853 1235 FNRFHCHFSPRDWQR X O56137 854 1236 FQERLQEDTSFGGNL X O56137 855 1237 FRPKRLNFKLFNIQV X O56137 856 1238 FSPRDWQRLINNNWG X O56137 857 1239 FTVDNNGLYTEPRPI X O56137 858 1240 FTWTGASKYNLNGRE X O56137 859 1241 GAPKPKANQQKQDDG X O56137 860 1242 GAPMADNNEGADGVG X O56137 861 1243 GASNTALDNVMITDE X O56137 862 1244 GHFHPSPLMGGFGLK X O56137 863 1245 GLDKGEPVNAADAAA X O56137 864 1246 GRGLVLPGYKYLGPF X O56137 865 1247 GYFDFNRFHCHFSPR X O56137 866 1248 GYKYLGPFNGLDKGE X O56137 867 1249 IEWELQKENSKRWNP X O56137 868 1250 IREWWDLKPGAPKPK X O56137 869 1251 KIPHTDGHFHPSPLM X O56137 870 1252 KKRPVEQSPQEPDSS X O56137 871 1253 KQDDGRGLVLPGYKY X O56137 872 1254 KTDNNNSNFTWTGAS X O56137 873 1255 LDKGEPVNAADAAAL X O56137 874 1256 LEHDKAYDQQLKAGD X O56137 875 1257 LEYFPSQMLRTGNNF X O56137 876 1258 LKPGAPKPKANQQKQ X O56137 877 1259 MASGGGAPMADNNEG X O56137 878 1260 NEGADGVGNASGNWH X O56137 879 1261 NGLDKGEPVNAADAA X O56137 880 1262 NGSQAVGRSSFYCLE X O56137 881 1263 NNSNFTWTGASKYNL X O56137 882 1264 NNWGFRPKRLNFKLF X O56137 883 1265 NPYLRYNHADAEFQE X O56137 884 1266 NVMITDEEEIKATNP X O56137 885 1267 NWGFRPKRLNFKLFN X O56137 886 1268 PADVFMIPQYGYLTL X O56137 887 1269 PDSSSGIGKTGQQPA X O56137 888 1270 PFNGLDKGEPVNAAD X O56137 889 1271 PGKKRPVEQSPQEPD X O56137 890 1272 PGYKYLGPFNGLDKG X O56137 891 1273 PIWAKIPHTDGHFHP X O56137 892 1274 PQILIKNTPVPANPP X O56137 893 1275 QEPDSSSGIGKTGQQ X O56137 894 1276 QISSASTGASNDNHY X O56137 895 1277 QQKQDDGRGLVLPGY X O56137 896 1278 REWWDLKPGAPKPKA X O56137 897 1279 RLMNPLIDQYLYYLN X O56137 898 1280 RLNFKLFNIQVKEVT X O56137 899 1281 SEYQLPYVLGSAHQG X O56137 900 1282 SGNWHCDSTWLGDRV X O56137 901 1283 SPRDWQRLINNNWGF X O56137 902 1284 STGQVSVEIEWELQK X O56137 903 1285 STPWGYFDFNRFHCH X O56137 904 1286 TALDNVMITDEEEIK X O56137 905 1287 TGDSESVPDPQPLGE X O56137 906 1288 VGNASGNWHCDSTWL X O56137 907 1289 WAKIPHTDGHFHPSP X O56137 908 1290 WELQKENSKRWNPEV X O56137 909 1291 YTEPRPIGTRYLTRP X O56137 910 1292 AGMSVQPKNWLPGPC X O56137 911 1293 AHSQSLDRLMNPLID X O56137 912 1294 APGKKRPVEQSPQEP X O56137 913 1295 APKPKANQQKQDDGR X O56137 914 1296 CDSTWLGDRVITTST X O56137 915 1297 CLEYFPSQMLRTGNN X O56137 916 1298 DGRGLVLPGYKYLGP X O56137 917 1299 DKAYDQQLKAGDNPY X O56137 918 1300 DQQLKAGDNPYLRYN X O56137 919 1301 DRDVYLQGPIWAKIP X O56137 920 1302 FPSQMLRTGNNFTFS X O56137 921 1303 GASKYNLNGRESIIN X O56137 922 1304 GDRVITTSTRTWALP X O56137 923 1305 GFRPKRLNFKLFNIQ X O56137 924 1306 GIREWWDLKPGAPKP X O56137 925 1307 GLVEEGAKTAPGKKR X O56137 926 1308 GLVLPGYKYLGPFNG X O56137 927 1309 GLYTEPRPIGTRYLT X O56137 928 1310 GNLGRAVFQAKKRVL X O56137 929 1311 GQTGDSESVPDPQPL X O56137 930 1312 GRESIINPGTAMASH X O56137 931 1313 HADAEFQERLQEDTS X O56137 932 1314 HFSPRDWQRLINNNW X O56137 933 1315 IKNTPVPANPPAEFS X O56137 934 1316 KANQQKQDDGRGLVL X O56137 935 1317 KPGAPKPKANQQKQD X O56137 936 1318 KPKANQQKQDDGRGL X O56137 937 1319 KRLNFGQTGDSESVP X O56137 938 1320 LDNVMITDEEEIKAT X O56137 939 1321 LGRAVFQAKKRVLEP X O56137 940 1322 LNFGQTGDSESVPDP X O56137 941 1323 LNGRESIINPGTAMA X O56137 942 1324 LNNGSQAVGRSSFYC X O56137 943 1325 LPGYKYLGPFNGLDK X O56137 944 1326 LPTYNNHLYKQISSA X O56137 945 1327 LRYNHADAEFQERLQ X O56137 946 1328 LVEEGAKTAPGKKRP X O56137 947 1329 MLRTGNNFTFSYTFE X O56137 948 1330 NFKLFNIQVKEVTTN X O56137 949 1331 NHADAEFQERLQEDT X O56137 950 1332 NLGRAVFQAKKRVLE X O56137 951 1333 PFHSSYAHSQSLDRL X O56137 952 1334 PKRLNFKLFNIQVKE X O56137 953 1335 PPATPAAVGPTTMAS X O56137 954 1336 PPPQILIKNTPVPAN X O56137 955 1337 PQYGYLTLNNGSQAV X O56137 956 1338 PRDWQRLINNNWGFR X O56137 957 1339 PYVLGSAHQGCLPPF X O56137 958 1340 QDDGRGLVLPGYKYL X O56137 959 1341 QDRDVYLQGPIWAKI X O56137 960 1342 QERLQEDTSFGGNLG X O56137 961 1343 QRLINNNWGFRPKRL X O56137 962 1344 QYLYYLNRTQNQSGS X O56137 963 1345 RDVYLQGPIWAKIPH X O56137 964 1346 RDWQRLINNNWGFRP X O56137 965 1347 RGSPAGMSVQPKNWL X O56137 966 1348 RLNFGQTGDSESVPD X O56137 967 1349 RLQEDTSFGGNLGRA X O56137 968 1350 RQQRVSKTKTDNNNS X O56137 969 1351 SEGIREWWDLKPGAP X O56137 970 1352 SKYNLNGRESIINPG X O56137 971 1353 SNFTWTGASKYNLNG X O56137 972 1354 SSFYCLEYFPSQMLR X O56137 973 1355 STRTWALPTYNNHLY X O56137 974 1356 TNPVATERFGTVAVN X O56137 975 1357 TSTRTWALPTYNNHL X O56137 976 1358 TTMASGGGAPMADNN X O56137 977 1359 TWLGDRVITTSTRTW X O56137 978 1360 TYNNHLYKQISSAST X O56137 979 1361 VDNNGLYTEPRPIGT X O56137 980 1362 VFMIPQYGYLTLNNG X O56137 981 1363 VNAADAAALEHDKAY X O56137 982 1364 VPFHSSYAHSQSLDR X O56137 983 1365 VQYTSNYAKSANVDF X O56137 984 1366 WGFRPKRLNFKLFNI X O56137 985 1367 WLGDRVITTSTRTWA X O56137 986 1368 WQDRDVYLQGPIWAK X O56137 987 1369 WQRLINNNWGFRPKR X O56137 988 1370 YAKSANVDFTVDNNG X O56137 989 1371 YGYLTLNNGSQAVGR X O56137 990 1372 YLNRTQNQSGSAQNK X O56137 991 1373 YLRYNHADAEFQERL X O56137 992 1374 YNLNGRESIINPGTA X O56137 993 1375 FQFSYTFEDVPFHSS X O56139 994 1376 QGALPGMVWQDRDVY X O56139 995 1377 NDQGALPGMVWQDRD X O56139 996 1378 EIRTTNPVATEQYGT X O56139 997 1379 EQYGTVANNLQSSNT X O56139 998 1380 PGNGLDKGEPVNEAD X O56139 999 1381 GEPPAAPTSLGSNTM X O56139 1000 1382 GSNTMASGGGAPMAD X O56139 1001 1383 NTMASGGGAPMADNN X O56139 1002 1384 PTTRTVNDQGALPGM X O56139 1003 1385 LGPGNGLDKGEPVNE X O56139 1004 1386 PDPQPLGEPPAAPTS X O56139 1005 1387 PVATEQYGTVANNLQ X O56139 1006 1388 QSMSLQARNWLPGPC X O56139 1007 1389 SGVGKSGKQPARKRL X O56139 1008 1390 TFSPAKFASFITQYS X O56139 1009 1391 TVNDQGALPGMVWQD X O56139 1010 1392 VGNSSGNWHCDSQWL X O56139 1011 1393 EWWALKPGVPQPKAN X O56139 1012 1394 FPWTAASKYHLNGRD X O56139 1013 1395 LINNNWGFRPKKLSF X O56139 1014 1396 MGGFGLKHPPPQIMI X O56139 1015 1397 NPPTTFSPAKFASFI X O56139 1016 1398 NWGFRPKKLSFKLFN X O56139 1017 1399 TNPVATEQYGTVANN X O56139 1018 1400 AAKTAPGKKRPVDQS X O56139 1019 1401 AAPTSLGSNTMASGG X O56139 1020 1402 AASKYHLNGRDSLVN X O56139 1021 1403 ANNLQSSNTAPTTRT X O56139 1022 1404 DQSPQEPDSSSGVGK X O56139 1023 1405 EGIREWWALKPGVPQ X O56139 1024 1406 GKQPARKRLNFGQTG X O56139 1025 1407 GPQSMSLQARNWLPG X O56139 1026 1408 GRAVFQAKKRILEPL X O56139 1027 1409 IKNTPVPANPPTTFS X O56139 1028 1410 IREWWALKPGVPQPK X O56139 1029 1411 KRILEPLGLVEEAAK X O56139 1030 1412 LKPGVPQPKANQQHQ X O56139 1031 1413 NLGRAVFQAKKRILE X O56139 1032 1414 PANPPTTFSPAKFAS X O56139 1033 1415 PQIMIKNTPVPANPP X O56139 1034 1416 QEPDSSSGVGKSGKQ X O56139 1035 1417 SKYHLNGRDSLVNPG X O56139 1036 1418 SLGSNTMASGGGAPM X O56139 1037 1419 SNTAPTTRTVNDQGA X O56139 1038 1420 TAPTTRTVNDQGALP X O56139 1039 1421 HKDDEEKFFPMHGNL X O56139 1040 1422 ASHKDDEEKFFPMHG X O56139 1041 1423 KFFPMHGNLIFGKEG X O56139 1042 1424 NVMITDEEEIRTTNP X O56139 1043 1425 AMASHKDDEEKFFPM X O56139 1044 1426 LDNVMITDEEEIRTT X O56139 1045 1427 FGKEGTTASNAELDN X O56139 1046 1428 KTANDNNNSNFPWTA X O56139 1047 1429 RQQRLSKTANDNNNS X O56139 1048 1430 DNNNSNFPWTAASKY X O56139 1049 1431 FPMHGNLIFGKEGTT X O56139 1050 1432 GNLIFGKEGTTASNA X O56139 1051 1433 KEGTTASNAELDNVM X O56139 1052 1434 LSKTANDNNNSNFPW X O56139 1053 1435 QGTTSGTTNQSRLLF X O56139 1054 1436 TASNAELDNVMITDE X O56139 1055 1437 YLYYLNRTQGTTSGT X O56139 1056 1438 YYLNRTQGTTSGTTN X O56139 1057 1439 QRLINNNWGFRPKKL X O56139 1058 1440 DGNFHPSPLMGGFGM X Q6JC40 1059 1441 GEDRFFPLSGSLIFG X Q6JC40 1060 1442 LEDNLSEGIREWWAL X Q6JC40 1061 1443 NDNAYFGYSTPWGYF X Q6JC40 1062 1444 NFQFSYEFENVPFHS X Q6JC40 1063 1445 NNLTSTVQVFTDSDY X Q6JC40 1064 1446 QGILPGMVWQDRDVY X Q6JC40 1065 1447 EGVYSEPRPIGTRYL X Q6JC40 1066 1448 GILPGMVWQDRDVYL X Q6JC40 1067 1449 NSEFAWPGASSWALN X Q6JC40 1068 1450 PYLKYNHADAEFQER X Q6JC40 1069 1451 KEGEDRFFPLSGSLI X Q6JC40 1070 1452 PGPAMASHKEGEDRF X Q6JC40 1071 1453 QAKKRLLEPLGLVEE X Q6JC40 1072 1454 QNQGILPGMVWQDRD X Q6JC40 1073 1455 EGADGVGSSSGNWHC X Q6JC40 1074 1456 HEGCLPPFPADVFMI X Q6JC40 1075 1457 LVEEAAKTAPGKKRP X Q6JC40 1076 1458 NQGILPGMVWQDRDV X Q6JC40 1077 1459 EVTDNNGVKTIANNL X Q6JC40 1078 1460 GADGVGSSSGNWHCD X Q6JC40 1079 1461 LTSTVQVFTDSDYQL X Q6JC40 1080 1462 NEGADGVGSSSGNWH X Q6JC40 1081 1463 NPVATESYGQVATNH X Q6JC40 1082 1464 NVDADKVMITNEEEI X Q6JC40 1083 1465 PVADNNEGADGVGSS X Q6JC40 1084 1466 SAHEGCLPPFPADVF X Q6JC40 1085 1467 TGDTESVPDPQPIGE X Q6JC40 1086 1468 TMASGGGAPVADNNE X Q6JC40 1087 1469 VEQSPQEPDSSAGIG X Q6JC40 1088 1470 VQVFTDSDYQLPYVL X Q6JC40 1089 1471 EPLGLVEEAAKTAPG X Q6JC40 1090 1472 EPPAAPSGVGSLTMA X Q6JC40 1091 1473 FNKDKLNSFITQYST X Q6JC40 1092 1474 GAPVADNNEGADGVG X Q6JC40 1093 1475 GGGAPVADNNEGADG X Q6JC40 1094 1476 IFGKQGTGRDNVDAD X Q6JC40 1095 1477 ILPGMVWQDRDVYLQ X Q6JC40 1096 1478 MGGFGMKHPPPQILI X Q6JC40 1097 1479 PPQILIKNTPVPADP X Q6JC40 1098 1480 RAVFQAKKRLLEPLG X Q6JC40 1099 1481 RDNVDADKVMITNEE X Q6JC40 1100 1482 SNNVEFAVNTEGVYS X Q6JC40 1101 1483 TEGVYSEPRPIGTRY X Q6JC40 1102 1484 TSGGSSNDNAYFGYS X Q6JC40 1103 1485 TVTQNNNSEFAWPGA X Q6JC40 1104 1486 VLPGYKYLGPGNGLD X Q6JC40 1105 1487 ADPPTAFNKDKLNSF X Q6JC40 1106 1488 ALNGRNSLMNPGPAM X Q6JC40 1107 1489 APSGVGSLTMASGGG X Q6JC40 1108 1490 DNLSEGIREWWALKP X Q6JC40 1109 1491 DPPTAFNKDKLNSFI X Q6JC40 1110 1492 DSQWLGDRVITTSTR X Q6JC40 1111 1493 DSSAGIGKSGAQPAK X Q6JC40 1112 1494 DVFMIPQYGYLTLND X Q6JC40 1113 1495 GIGKSGAQPAKKRLN X Q6JC40 1114 1496 GKQGTGRDNVDADKV X Q6JC40 1115 1497 GNFHPSPLMGGFGMK X Q6JC40 1116 1498 GVGSSSGNWHCDSQW X Q6JC40 1117 1499 ISNSTSGGSSNDNAY X Q6JC40 1118 1500 KLNSFITQYSTGQVS X Q6JC40 1119 1501 KNTPVPADPPTAFNK X Q6JC40 1120 1502 KYLGPGNGLDKGEPV X Q6JC40 1121 1503 LGRAVFQAKKRLLEP X Q6JC40 1122 1504 LGSAHEGCLPPFPAD X Q6JC40 1123 1505 MNPGPAMASHKEGED X Q6JC40 1124 1506 NMAVQGRNYIPGPSY X Q6JC40 1125 1507 NNEGADGVGSSSGNW X Q6JC40 1126 1508 NWHCDSQWLGDRVIT X Q6JC40 1127 1509 PAMASHKEGEDRFFP X Q6JC40 1128 1510 PEIQYTSNYYKSNNV X Q6JC40 1129 1511 QQRVSTTVTQNNNSE X Q6JC40 1130 1512 RLLEPLGLVEEAAKT X Q6JC40 1131 1513 RPVEQSPQEPDSSAG X Q6JC40 1132 1514 TAFNKDKLNSFITQY X Q6JC40 1133 1515 TGWVQNQGILPGMVW X Q6JC40 1134 1516 TQNNNSEFAWPGASS X Q6JC40 1135 1517 VKEVTDNNGVKTIAN X Q6JC40 1136 1518 VPDPQPIGEPPAAPS X Q6JC40 1137 1519 VQNQGILPGMVWQDR X Q6JC40 1138 1520 YFPSQMLRTGNNFQF X Q6JC40 1139 1521 YVLGSAHEGCLPPFP X Q6JC40 1140 1522 ADGVGSSSGNWHCDS X Q6JC40 1141 1523 ANQQHQDNARGLVLP X Q6JC40 1142 1524 AQPAKKRLNFGQTGD X Q6JC40 1143 1525 ARGLVLPGYKYLGPG X Q6JC40 1144 1526 ASSWALNGRNSLMNP X Q6JC40 1145 1527 AVNTEGVYSEPRPIG X Q6JC40 1146 1528 DNNEGADGVGSSSGN X Q6JC40 1147 1529 DPQPIGEPPAAPSGV X Q6JC40 1148 1530 DRFFPLSGSLIFGKQ X Q6JC40 1149 1531 FGMKHPPPQILIKNT X Q6JC40 1150 1532 GLVLPGYKYLGPGNG X Q6JC40 1151 1533 GNLGRAVFQAKKRLL X Q6JC40 1152 1534 GPGNGLDKGEPVNAA X Q6JC40 1153 1535 GQTGDTESVPDPQPI X Q6JC40 1154 1536 GSSSGNWHCDSQWLG X Q6JC40 1155 1537 GWVQNQGILPGMVWQ X Q6JC40 1156 1538 IANNLTSTVQVFTDS X Q6JC40 1157 1539 KKRLLEPLGLVEEAA X Q6JC40 1158 1540 KKRLNFGQTGDTESV X Q6JC40 1159 1541 LEPLGLVEEAAKTAP X Q6JC40 1160 1542 LGLVEEAAKTAPGKK X Q6JC40 1161 1543 LKAGDNPYLKYNHAD X Q6JC40 1162 1544 LMGGFGMKHPPPQIL X Q6JC40 1163 1545 LNDGSQAVGRSSFYC X Q6JC40 1164 1546 LPYVLGSAHEGCLPP X Q6JC40 1165 1547 LSEGIREWWALKPGA X Q6JC40 1166 1548 MKHPPPQILIKNTPV X Q6JC40 1167 1549 NLSEGIREWWALKPG X Q6JC40 1168 1550 NSTSGGSSNDNAYFG X Q6JC40 1169 1551 NTEGVYSEPRPIGTR X Q6JC40 1170 1552 NYYKSNNVEFAVNTE X Q6JC40 1171 1553 PADPPTAFNKDKLNS X Q6JC40 1172 1554 PAKKRLNFGQTGDTE X Q6JC40 1173 1555 PLIDQYLYYLSKTIN X Q6JC40 1174 1556 PLMGGFGMKHPPPQI X Q6JC40 1175 1557 PQEPDSSAGIGKSGA X Q6JC40 1176 1558 PQPKANQQHQDNARG X Q6JC40 1177 1559 PSPLMGGFGMKHPPP X Q6JC40 1178 1560 PSQMLRTGNNFQFSY X Q6JC40 1179 1561 PSYRQQRVSTTVTQN X Q6JC40 1180 1562 QNQQTLKFSVAGPSN X Q6JC40 1181 1563 QTGWVQNQGILPGMV X Q6JC40 1182 1564 QYTSNYYKSNNVEFA X Q6JC40 1183 1565 RLMNPLIDQYLYYLS X Q6JC40 1184 1566 RLNFGQTGDTESVPD X Q6JC40 1185 1567 RNSLMNPGPAMASHK X Q6JC40 1186 1568 SAQAQAQTGWVQNQG X Q6JC40 1187 1569 SGNWHCDSQWLGDRV X Q6JC40 1188 1570 SHKEGEDRFFPLSGS X Q6JC40 1189 1571 SLMNPGPAMASHKEG X Q6JC40 1190 1572 SQMLRTGNNFQFSYE X Q6JC40 1191 1573 TDSDYQLPYVLGSAH X Q6JC40 1192 1574 TESYGQVATNHQSAQ X Q6JC40 1193 1575 TLKFSVAGPSNMAVQ X Q6JC40 1194 1576 TSNYYKSNNVEFAVN X Q6JC40 1195 1577 VFTDSDYQLPYVLGS X Q6JC40 1196 1578 VGSLTMASGGGAPVA X Q6JC40 1197 1579 VPADPPTAFNKDKLN X Q6JC40 1198 1580 WVQNQGILPGMVWQD X Q6JC40 1199 1581 WWALKPGAPQPKANQ X Q6JC40 1200 1582 YDQQLKAGDNPYLKY X Q6JC40 1201 1583 YKYLGPGNGLDKGEP X Q6JC40 1202 1584 YLGPGNGLDKGEPVN X Q6JC40 1203 1585 YRQQRVSTTVTQNNN X Q6JC40 1204 1586 YYKSNNVEFAVNTEG X Q6JC40 1205 1587 TDGNFHPSPLMGGFG X Q6JC40 1206 1588 WELQKENSKRWNPEI X Q6JC40 1207 1589 HTDGNFHPSPLMGGF X Q6JC40 1208 1590 PHTDGNFHPSPLMGG X Q6JC40 1209 1591 AKIPHTDGNFHPSPL X Q6JC40 1210 1592 QKENSKRWNPEIQYT X Q6JC40 1211 1593 GPIWAKIPHTDGNFH X Q6JC40 1212 1594 GVYSEPRPIGTRYLT X Q6JC40 1213 1595 KENSKRWNPEIQYTS X Q6JC40 1214 1596 KIPHTDGNFHPSPLM X Q6JC40 1215 1597 LQKENSKRWNPEIQY X Q6JC40 1216 1598 PIWAKIPHTDGNFHP X Q6JC40 1217 1599 TIQVFTDSEYQLPYV X Q8JQF8 1218 1600 NNLTSTIQVFTDSEY X Q8JQF8 1219 1601 HKDDEERFFPSNGIL X Q8JQF8 1220 1602 SSGNWHCDSTWLGDR X Q8JQF8 1221 1603 ATNDNTYFGYSTPWG X Q8JQF8 1222 1604 NFQFTYTFEDVPFHS X Q8JQF8 1223 1605 TAPGKKRPVEPSPQR X Q8JQF8 1224 1606 AALEHDKAYDQQLQA X Q8JQF8 1225 1607 ADYSDVMLTSEEEIK X Q8JQF8 1226 1608 ATHKDDEERFFPSNG X Q8JQF8 1227 1609 EPPAAPSGVGPNTMA X Q8JQF8 1228 1610 EWWALKPGAPKPKAN X Q8JQF8 1229 1611 FGKQNAARDNADYSD X Q8JQF8 1230 1612 MAAGGGAPMADNNEG X Q8JQF8 1231 1613 PQIGTVNSQGALPGM X Q8JQF8 1232 1614 QVFTDSEYQLPYVLG X Q8JQF8 1233 1615 VGSSSGNWHCDSTWL X Q8JQF8 1234 1616 ANNLTSTIQVFTDSE X Q8JQF8 1235 1617 GIAMATHKDDEERFF X Q8JQF8 1236 1618 GVGSSSGNWHCDSTW X Q8JQF8 1237 1619 IDQYLYYLSRTQTTG X Q8JQF8 1238 1620 IQVFTDSEYQLPYVL X Q8JQF8 1239 1621 RQQRVSTTTGQNNNS X Q8JQF8 1240 1622 TAPQIGTVNSQGALP X Q8JQF8 1241 1623 YDQQLQAGDNPYLRY X Q8JQF8 1242 1624 ATEEYGIVADNLQQQ X Q8JQF8 1243 1625 EGAKTAPGKKRPVEP X Q8JQF8 1244 1626 EVTQNEGTKTIANNL X Q8JQF8 1245 1627 FKLFNIQVKEVTQNE X Q8JQF8 1246 1628 FPSQMLRTGNNFQFT X Q8JQF8 1247 1629 GPNTMANQAKNWLPG X Q8JQF8 1248 1630 LEHDKAYDQQLQAGD X Q8JQF8 1249 1631 LIFGKQNAARDNADY X Q8JQF8 1250 1632 LTSTIQVFTDSEYQL X Q8JQF8 1251 1633 LYKQISNGTSGGATN X Q8JQF8 1252 1634 MANQAKNWLPGPCYR X Q8JQF8 1253 1635 NLTSTIQVFTDSEYQ X Q8JQF8 1254 1636 NPGIAMATHKDDEER X Q8JQF8 1255 1637 NQSKLNSFITQYSTG X Q8JQF8 1256 1638 PNTMAAGGGAPMADN X Q8JQF8 1257 1639 SFKLFNIQVKEVTQN X Q8JQF8 1258 1640 TDSEYQLPYVLGSAH X Q8JQF8 1259 1641 TMAAGGGAPMADNNE X Q8JQF8 1260 1642 AMATHKDDEERFFPS X Q8JQF8 1261 1643 APSGVGPNTMAAGGG X Q8JQF8 1262 1644 DPPTTFNQSKLNSFI X Q8JQF8 1263 1645 DPQPLGEPPAAPSGV X Q8JQF8 1264 1646 EGIREWWALKPGAPK X Q8JQF8 1265 1647 FPSNGILIFGKQNAA X Q8JQF8 1266 1648 FTDSEYQLPYVLGSA X Q8JQF8 1267 1649 GAKTAPGKKRPVEPS X Q8JQF8 1268 1650 GGTANTQTLGFSQGG X Q8JQF8 1269 1651 GILIFGKQNAARDNA X Q8JQF8 1270 1652 GTKTIANNLTSTIQV X Q8JQF8 1271 1653 INNNWGFRPKRLSFK X Q8JQF8 1272 1654 IQYTSNYYKSTSVDF X Q8JQF8 1273 1655 ISNGTSGGATNDNTY X Q8JQF8 1274 1656 KAYDQQLQAGDNPYL X Q8JQF8 1275 1657 KEVTQNEGTKTIANN X Q8JQF8 1276 1658 KLFNIQVKEVTQNEG X Q8JQF8 1277 1659 KSTSVDFAVNTEGVY X Q8JQF8 1278 1660 KTIANNLTSTIQVFT X Q8JQF8 1279 1661 KTTNPVATEEYGIVA X Q8JQF8 1280 1662 LMNPLIDQYLYYLSR X Q8JQF8 1281 1663 LPTYNNHLYKQISNG X Q8JQF8 1282 1664 LTSEEEIKTTNPVAT X Q8JQF8 1283 1665 MADNNEGADGVGSSS X Q8JQF8 1284 1666 NGTSGGATNDNTYFG X Q8JQF8 1285 1667 NHLYKQISNGTSGGA X Q8JQF8 1286 1668 NIQVKEVTQNEGTKT X Q8JQF8 1287 1669 NLQQQNTAPQIGTVN X Q8JQF8 1288 1670 NNHLYKQISNGTSGG X Q8JQF8 1289 1671 NTMANQAKNWLPGPC X Q8JQF8 1290 1672 PEIQYTSNYYKSTSV X Q8JQF8 1291 1673 PGKKRPVEPSPQRSP X Q8JQF8 1292 1674 PTYNNHLYKQISNGT X Q8JQF8 1293 1675 QGGPNTMANQAKNWL X Q8JQF8 1294 1676 QNEGTKTIANNLTST X Q8JQF8 1295 1677 QNNNSNFAWTAGTKY X Q8JQF8 1296 1678 QNTAPQIGTVNSQGA X Q8JQF8 1297 1679 QPLGEPPAAPSGVGP X Q8JQF8 1298 1680 QTLGFSQGGPNTMAN X Q8JQF8 1299 1681 QVKEVTQNEGTKTIA X Q8JQF8 1300 1682 SGVGPNTMAAGGGAP X Q8JQF8 1301 1683 SNFAWTAGTKYHLNG X Q8JQF8 1302 1684 SQGALPGMVWQNRDV X Q8JQF8 1303 1685 TQNEGTKTIANNLTS X Q8JQF8 1304 1686 TSGGATNDNTYFGYS X Q8JQF8 1305 1687 TSTIQVFTDSEYQLP X Q8JQF8 1306 1688 TYNNHLYKQISNGTS X Q8JQF8 1307 1689 VGPNTMAAGGGAPMA X Q8JQF8 1308 1690 VMLTSEEEIKTTNPV X Q8JQF8 1309 1691 WLPGPCYRQQRVSTT X Q8JQF8 1310 1692 YLSRTQTTGGTANTQ X Q8JQF8 1311 1693 YYKSTSVDFAVNTEG X Q8JQF8 1312 1694 DGNFHPSPLMGGFGL X Q8JQF8 1313 1695 NDNTYFGYSTPWGYF X Q8JQF8 1314 1696 GALPGMVWQNRDVYL X Q8JQF8 1315 1697 AGGGAPMADNNEGAD X Q8JQF8 1316 1698 RPVEPSPQRSPDSST X Q8JQF8 1317 1699 MVWQNRDVYLQGPIW X Q8JQF8 1318 1700 TNDNTYFGYSTPWGY X Q8JQF8 1319 1701 KRPVEPSPQRSPDSS X Q8JQF8 1320 1702 LPGMVWQNRDVYLQG X Q8JQF8 1321 1703 VPDPQPLGEPPAAPS X Q8JQF8 1322 1704 VWQNRDVYLQGPIWA X Q8JQF8 1323 1705 AAGGGAPMADNNEGA X Q8JQF8 1324 1706 DSSTGIGKKGQQPAR X Q8JQF8 1325 1707 GKKGQQPARKRLNFG X Q8JQF8 1326 1708 NFHPSPLMGGFGLKH X Q8JQF8 1327 1709 QGALPGMVWQNRDVY X Q8JQF8 1328 1710 QQPARKRLNFGQTGD X Q8JQF8 1329 1711 ALPGMVWQNRDVYLQ X Q8JQF8 1330 1712 GIGKKGQQPARKRLN X Q8JQF8 1331 1713 GMVWQNRDVYLQGPI X Q8JQF8 1332 1714 GNFHPSPLMGGFGLK X Q8JQF8 1333 1715 KKRPVEPSPQRSPDS X Q8JQF8 1334 1716 PDSSTGIGKKGQQPA X Q8JQF8 1335 1717 PGMVWQNRDVYLQGP X Q8JQF8 1336 1718 QRSPDSSTGIGKKGQ X Q8JQF8 1337 1719 VEPSPQRSPDSSTGI X Q8JQF8 1338 1720 QAKKRVLEPLGLVEE X Q8JQF8 1339 1721 EPLGLVEEGAKTAPG X Q8JQF8 1340 1722 RAVFQAKKRVLEPLG X Q8JQF8 1341 1723 AKKRVLEPLGLVEEG X Q8JQF8 1342 1724 FQAKKRVLEPLGLVE X Q8JQF8 1343 1725 PLGLVEEGAKTAPGK X Q8JQF8 1344 1726 RVLEPLGLVEEGAKT X Q8JQF8 1345 1727 GYSTPWGYFDFNRFH X Q9YIJ1 1346 1728 FEFTYNFEEVPFHSS X Q9YIJ1 1347 1729 NPTERSSFFCLEYFP X Q9YIJ1 1348 1730 GDWHCDSTWMGDRVV X Q9YIJ1 1349 1731 TVQVFTDDDYQLPYV X Q9YIJ1 1350 1732 FTYNFEEVPFHSSFA X Q9YIJ1 1351 1733 VDHPPDWLEEVGEGL X Q9YIJ1 1352 1734 RSSFFCLEYFPSKML X Q9YIJ1 1353 1735 TGAHFHPSPAMGGFG X Q9YIJ1 1354 1736 ASGDWHCDSTWMGDR X Q9YIJ1 1355 1737 GVGNASGDWHCDSTW X Q9YIJ1 1356 1738 PQFVDFAPDSTGEYR X Q9YIJ1 1357 1739 RGEPVNRADEVAREH X Q9YIJ1 1358 1740 AYFGYSTPWGYFDFN X Q9YIJ1 1359 1741 DNTENPTERSSFFCL X Q9YIJ1 1360 1742 DYQLPYVVGNGTEGC X Q9YIJ1 1361 1743 PETGAHFHPSPAMGG X Q9YIJ1 1362 1744 RADEVAREHDISYNE X Q9YIJ1 1363 1745 TERSSFFCLEYFPSK X Q9YIJ1 1364 1746 EGLREFLGLEAGPPK X Q9YIJ1 1365 1747 NDPQFVDFAPDSTGE X Q9YIJ1 1366 1748 PAMGGFGLKHPPPMM X Q9YIJ1 1367 1749 VAREHDISYNEQLEA X Q9YIJ1 1368 1750 VNRADEVAREHDISY X Q9YIJ1 1369 1751 YNHADAEFQEKLADD X Q9YIJ1 1370 1752 EPFGLVEEGAKTAPT X Q9YIJ1 1371 1753 FSDVPVSSFITQYST X Q9YIJ1 1372 1754 FTDDDYQLPYVVGNG X Q9YIJ1 1373 1755 HADAEFQEKLADDTS X Q9YIJ1 1374 1756 MGGFGLKHPPPMMLI X Q9YIJ1 1375 1757 NGLDRGEPVNRADEV X Q9YIJ1 1376 1758 NPEIQYTNNYNDPQF X Q9YIJ1 1377 1759 QVFTDDDYQLPYVVG X Q9YIJ1 1378 1760 REHDISYNEQLEAGD X Q9YIJ1 1379 1761 VGEGLREFLGLEAGP X Q9YIJ1 1380 1762 WGYFDFNRFHSHWSP X Q9YIJ1 1381 1763 WSPRDWQRLINNYWG X Q9YIJ1 1382 1764 YFDFNRFHSHWSPRD X Q9YIJ1 1383 1765 ADGVGNASGDWHCDS X Q9YIJ1 1384 1766 ARTEEDSKPSTSSDA X Q9YIJ1 1385 1767 ASVSAFATTNRMELE X Q9YIJ1 1386 1768 DFNRFHSHWSPRDWQ X Q9YIJ1 1387 1769 EGCLPAFPPQVFTLP X Q9YIJ1 1388 1770 ETQPVNRVAYNVGGQ X Q9YIJ1 1389 1771 FHPSPAMGGFGLKHP X Q9YIJ1 1390 1772 GGGGPLGDNNQGADG X Q9YIJ1 1391 1773 GGPLGDNNQGADGVG X Q9YIJ1 1392 1774 IDDHFPKRKKARTEE X Q9YIJ1 1393 1775 LVEEGAKTAPTGKRI X Q9YIJ1 1394 1776 NLQEIVPGSVWMERD X Q9YIJ1 1395 1777 NPYLKYNHADAEFQE X Q9YIJ1 1396 1778 PAFPPQVFTLPQYGY X Q9YIJ1 1397 1779 PASSLGADTMSAGGG X Q9YIJ1 1398 1780 PVSSFITQYSTGQVT X Q9YIJ1 1399 1781 QGADGVGNASGDWHC X Q9YIJ1 1400 1782 TGGVQFNKNLAGRYA X Q9YIJ1 1401 1783 VSAFATTNRMELEGA X Q9YIJ1 1402 1784 YFPSKMLRTGNNFEF X Q9YIJ1 1403 1785 YNFEEVPFHSSFAPS X Q9YIJ1 1404 1786 AFATTNRMELEGASY X Q9YIJ1 1405 1787 AHFHPSPAMGGFGLK X Q9YIJ1 1406 1788 DFAPDSTGEYRTTRP X Q9YIJ1 1407 1789 DGSNANAYFGYSTPW X Q9YIJ1 1408 1790 DNPYLKYNHADAEFQ X Q9YIJ1 1409 1791 DSTGEYRTTRPIGTR X Q9YIJ1 1410 1792 EGNMLITSESETQPV X Q9YIJ1 1411 1793 FVSTNNTGGVQFNKN X Q9YIJ1 1412 1794 GDNPYLKYNHADAEF X Q9YIJ1 1413 1795 GGNLGKAVFQAKKRV X Q9YIJ1 1414 1796 GTEGCLPAFPPQVFT X Q9YIJ1 1415 1797 HDISYNEQLEAGDNP X Q9YIJ1 1416 1798 IVPGSVWMERDVYLQ X Q9YIJ1 1417 1799 KIPETGAHFHPSPAM X Q9YIJ1 1418 1800 KMLRTGNNFEFTYNF X Q9YIJ1 1419 1801 LEAGPPKPKPNQQHQ X Q9YIJ1 1420 1802 LEYFPSKMLRTGNNF X Q9YIJ1 1421 1803 LGPGNGLDRGEPVNR X Q9YIJ1 1422 1804 LPGYNYLGPGNGLDR X Q9YIJ1 1423 1805 LVDQYLYRFVSTNNT X Q9YIJ1 1424 1806 NIQVKEVTVQDSTTT X Q9YIJ1 1425 1807 NITSFSDVPVSSFIT X Q9YIJ1 1426 1808 NNQGADGVGNASGDW X Q9YIJ1 1427 1809 NRASVSAFATTNRME X Q9YIJ1 1428 1810 NTPVPGNITSFSDVP X Q9YIJ1 1429 1811 NYLGPGNGLDRGEPV X Q9YIJ1 1430 1812 PATGTYNLQEIVPGS X Q9YIJ1 1431 1813 PGNGLDRGEPVNRAD X Q9YIJ1 1432 1814 PGNITSFSDVPVSSF X Q9YIJ1 1433 1815 PRDWQRLINNYWGFR X Q9YIJ1 1434 1816 PSPAMGGFGLKHPPP X Q9YIJ1 1435 1817 PYVVGNGTEGCLPAF X Q9YIJ1 1436 1818 QARGLVLPGYNYLGP X Q9YIJ1 1437 1819 QEKLADDTSFGGNLG X Q9YIJ1 1438 1820 QLPYVVGNGTEGCLP X Q9YIJ1 1439 1821 RMELEGASYQVPPQP X Q9YIJ1 1440 1822 SVWMERDVYLQGPIW X Q9YIJ1 1441 1823 TGEYRTTRPIGTRYL X Q9YIJ1 1442 1824 TTTIANNLTSTVQVF X Q9YIJ1 1443 1825 VVGNGTEGCLPAFPP X Q9YIJ1 1444 1826 WMERDVYLQGPIWAK X Q9YIJ1 1445 1827 WMGDRVVTKSTRTWV X Q9YIJ1 1446 1828 YLYRFVSTNNTGGVQ X Q9YIJ1 1447 1829 ADDTSFGGNLGKAVF X Q9YIJ1 1448 1830 AKKRVLEPFGLVEEG X Q9YIJ1 1449 1831 ALENTMIFNSQPANP X Q9YIJ1 1450 1832 APDSTGEYRTTRPIG X Q9YIJ1 1451 1833 APSQNLFKLANPLVD X Q9YIJ1 1452 1834 APTGKRIDDHFPKRK X Q9YIJ1 1453 1835 ASYQVPPQPNGMTNN X Q9YIJ1 1454 1836 ATNNQSSTTAPATGT X Q9YIJ1 1455 1837 DHFPKRKKARTEEDS X Q9YIJ1 1456 1838 DTSFGGNLGKAVFQA X Q9YIJ1 1457 1839 DVPVSSFITQYSTGQ X Q9YIJ1 1458 1840 DWQRLINNYWGFRPR X Q9YIJ1 1459 1841 FPPQVFTLPQYGYAT X Q9YIJ1 1460 1842 FQAKKRVLEPFGLVE X Q9YIJ1 1461 1843 GDNNQGADGVGNASG X Q9YIJ1 1462 1844 GDRVVTKSTRTWVLP X Q9YIJ1 1463 1845 GFRPRSLRVKIFNIQ X Q9YIJ1 1464 1846 GGQMATNNQSSTTAP X Q9YIJ1 1465 1847 GSGVNRASVSAFATT X Q9YIJ1 1466 1848 GSQQLQIPAQPASSL X Q9YIJ1 1467 1849 GVNRASVSAFATTNR X Q9YIJ1 1468 1850 IKSGSVDGSNANAYF X Q9YIJ1 1469 1851 KEVTVQDSTTTIANN X Q9YIJ1 1470 1852 KKENSKRWNPEIQYT X Q9YIJ1 1471 1853 LDRGEPVNRADEVAR X Q9YIJ1 1472 1854 LGADTMSAGGGGPLG X Q9YIJ1 1473 1855 LINNYWGFRPRSLRV X Q9YIJ1 1474 1856 LREFLGLEAGPPKPK X Q9YIJ1 1475 1857 LVLPGYNYLGPGNGL X Q9YIJ1 1476 1858 NLAGRYANTYKNWFP X Q9YIJ1 1477 1859 NLFKLANPLVDQYLY X Q9YIJ1 1478 1860 NNQSSTTAPATGTYN X Q9YIJ1 1479 1861 NNTGGVQFNKNLAGR X Q9YIJ1 1480 1862 NPLVDQYLYRFVSTN X Q9YIJ1 1481 1863 NRDNTENPTERSSFF X Q9YIJ1 1482 1864 PFHSSFAPSQNLFKL X Q9YIJ1 1483 1865 PIWAKIPETGAHFHP X Q9YIJ1 1484 1866 PLGDNNQGADGVGNA X Q9YIJ1 1485 1867 PMGRTQGWNLGSGVN X Q9YIJ1 1486 1868 PMMLIKNTPVPGNIT X Q9YIJ1 1487 1869 PQPNGMTNNLQGSNT X Q9YIJ1 1488 1870 QGPIWAKIPETGAHF X Q9YIJ1 1489 1871 QGSNTYALENTMIFN X Q9YIJ1 1490 1872 QPVNRVAYNVGGQMA X Q9YIJ1 1491 1873 QVKEVTVQDSTTTIA X Q9YIJ1 1492 1874 REIKSGSVDGSNANA X Q9YIJ1 1493 1875 RTTRPIGTRYLTRPL X Q9YIJ1 1494 1876 RWNPEIQYTNNYNDP X Q9YIJ1 1495 1877 RYANTYKNWFPGPMG X Q9YIJ1 1496 1878 SFFCLEYFPSKMLRT X Q9YIJ1 1497 1879 SFGGNLGKAVFQAKK X Q9YIJ1 1498 1880 SNANAYFGYSTPWGY X Q9YIJ1 1499 1881 SNTYALENTMIFNSQ X Q9YIJ1 1500 1882 SQNLFKLANPLVDQY X Q9YIJ1 1501 1883 SVDGSNANAYFGYST X Q9YIJ1 1502 1884 TGTYNLQEIVPGSVW X Q9YIJ1 1503 1885 TLNRDNTENPTERSS X Q9YIJ1 1504 1886 TSESETQPVNRVAYN X Q9YIJ1 1505 1887 TYKNWFPGPMGRTQG X Q9YIJ1 1506 1888 YATLNRDNTENPTER X Q9YIJ1 1507 1889 YGYATLNRDNTENPT X Q9YIJ1 1508 1890 YRFVSTNNTGGVQFN X Q9YIJ1 1509 1891 YSTPWGYFDFNRFHS X Q9YIJ1

Example 19: Screen for Anti-AAV Antibodies in Human Sera Based on Cyclic Peptides

[0428] More than 1200 cyclic peptides derived from the sequences of human and rhesus monkey AAV sequences and artificial AAV sequences according to Table 2 and with a sequence length of 14 amino-acids each were synthesized.

[0429] Samples obtained from human donors were screened for antibodies against these AAV-derived peptides immobilized on microarrays. To this end, IgG was prepared from blood obtained from the human donors by protein G purification. Each IgG sample was incubated with the peptide microarrays and Ig binding signals were detected by fluorescence. All antibody binding signals to the peptides on the arrays were background subtracted and ranked for each sample and a deduplicated aggregate of the respective top 250 peptide hits for each donor with the corresponding protein sequence of origin (as obtained from UniProt or other sources) was compiled (designated as group II). Further, the deduplicated aggregate of the respective top 50 peptide hits for each donor was compiled and designated as group I.

[0430] Detailed results are shown in Table 2 below. Altogether, group I contains 47 distinct peptide hits (assigned to the corresponding AAV vectors in Table 2) and group II yielded 172 distinct peptide hits. Evidently, group I is a subset of group II.

[0431] Thus, all listed peptides, preferably peptides belonging to group I, provide sequences from which shorter peptide sequences can be derived for antibody depletion according to the present invention. Furthermore, also other peptide sequences (or fragments) from the proteins from which the peptides of Table 2 were derived (preferably from group I), are suited to be used for SADCs according to the present invention. In addition, these peptides can also be used as probes for the diagnostic detection of anti-AAV antibodies in biological samples such as human sera.

Table 2

[0432] This table lists the detailed results of a screen for circularized peptides as a basis for the construction of anti-AAV antibody depleting SADCs according to the present invention. These peptides are also suitable for typing neutralizing antibodies directed against AAV gene therapy vectors. If not stated otherwise, the peptides represent fragments from different AAV VP1 proteins. Source given is either UniProt ID, GenBank ID, PDB ID or AAV strain name.

TABLE-US-00015 peptide # SEQ ID NO peptide group I group II source 1 1892 DSQWLGDRVITTST X X AAVLK03.L125I 2 1893 DTNGVYSEPRPIGT X X AAVLK03.L1251 3 1894 STNLQRGNLALGET X X AOD99651.1 4 1895 ANNLTSTVQIFADS X X A9RAI0 5 1896 KIFNIQVKEVTTSN X X A9RAI0 6 1897 GNTSQQQTDRNAFY X X 041855 7 1898 LEDNLSEGIREWWD X X AAO88201.1 8 1899 SESVPDPQPIGEPP X X AAO88201.1 9 1900 LIKNTPVPADPPTT X X AAO88201.1 10 1901 PQYGYLTLNNGSQA X X AAO88201.1 11 1902 DEEEIRTTNPVATE X X AAVLK03.L125I 12 1903 NYNKSVNVDFTVDT X X AAVLK03.L125I 13 1904 YHLNGRDSLVNPGP X X AAVLK03.L125I 14 1905 TRPATAPQIGTVNS X X AOD99652.1 15 1906 GETTRPATAAQTQV X X AOD99656.1 16 1907 IFNIQVKEVTTSNG X X A9RAI0 17 1908 SNSQLIFAGPNPSG X X A9RAI0 18 1909 TTTSSNNLLFTSEE X X A9RAI0 19 1910 FNIQVKEVTTNDGV X X 056137 20 1911 GQTGDSESVPDPQP X X AAO88201.1 21 1912 PQILIKNTPVPADP X X AAO88201.1 22 1913 QLKAGDNPYLRYNH X X AAO88201.1 23 1914 SFITQYSTGQVSVE X X AAO88201.1 24 1915 FGKQGAGRDNVDYS X X AAS99285.1 25 1916 YYKSTNVDFAVNTE X X AAS99285.1 26 1917 HYFGYSTPWGYFDF X X AAVLK03.L125I 27 1918 APGKKRPVDQSPQE X X AAVLK03.L125I 28 1919 GKKRPVDQSPQEPD X X AAVLK03.L125I 29 1920 KTAPGKKRPVDQSP X X AAVLK03.L125I 30 1921 PEIQYTSNYNKSVN X X AAVLK03.L125I 31 1922 SESVPDPQPLGEPP X X AAVLK03.L125I 32 1923 TAPGKKRPVDQSPQ X X AAVLK03.L1251 33 1924 YDQQLKAGDNPYLK X X AAVLK03.L125I 34 1925 YLYYLNRTQGTTSG X X AAVLK03.L125I 35 1926 DKAYDRQLDSGDNP X X AAV2i8 36 1927 GTNTMATGSGAPMA X X AAV2i8 37 1928 DKAYDQQLQAGDNP X X AAV-Rh74 38 1929 TESVPDPQPIGEPP X X ALU85156.1 39 1930 KNTPVPADPPTTES X X AAO88201.1 40 1931 PVPADPPTTESQAK X X AAO88201.1 41 1932 DEEEIKATNPVATE X X 056137 42 1933 DKDKFFPMSGVMIF X X 056137 43 1934 LQQQNTAPQIGTVN X X Q8JQF8 44 1935 EEEIKTTNPVATEE X X Q8JQF8 45 1936 GQNNNSNFAWTAGT X X Q8JQF8 46 1937 DDEDKFFPMSGVMI X X Q9WBP8 47 1938 PLVDQYLYRFVSTN X X Q9YIJ1 48 1939 ADPPTTFSQAKLAS X AAO88201.1 49 1940 DAAALEHDKAYDQQ X AAO88201.1 50 1941 DKAYDQQLKAGDNP X AAO88201.1 51 1942 DSESVPDPQPIGEP X AAO88201.1 52 1943 DWLEDNLSEGIREW X AAO88201.1 53 1944 EDNLSEGIREWWDL X AAO88201.1 54 1945 EEIKTTNPVATEQY X AAO88201.1 55 1946 ENSKRWNPEIQYTS X AAO88201.1 56 1947 ESVPDPQPIGEPPA X AAO88201.1 57 1948 EYQLPYVLGSAHQG X AAO88201.1 58 1949 FQERLQEDTSFGGN X AAO88201.1 59 1950 GDSESVPDPQPIGE X AAO88201.1 60 1951 HSQSLDRLMNPLID X AAO88201.1 61 1952 KGEPVNAADAAALE X AAO88201.1 62 1953 KNTPVPADPPTTFS X AAO88201.1 63 1954 LPYVLGSAHQGCLP X AAO88201.1 64 1955 LQQQNAAPIVGAVN X AAO88201.1 65 1956 NAADAAALEHDKAY X AAO88201.1 66 1957 NPGVAMATHKDDEE X AAO88201.1 67 1958 PGAPKPKANQQKQD X AAO88201.1 68 1959 PPQILIKNTPVPAD X AAO88201.1 69 1960 PRDWQRLINNNWGF X AAO88201.1 70 1961 PWGYFDFNRFHCHF X AAO88201.1 71 1962 QLPYVLGSAHQGCL X AAO88201.1 72 1963 QQRVSTTLSQNNNS X AAO88201.1 73 1964 SEPRPIGTRYLTRN X AAO88201.1 74 1965 SGGSTNDNTYFGYS X AAO88201.1 75 1966 SQSLDRLMNPLIDQ X AAO88201.1 76 1967 TGDSESVPDPQPIG X AAO88201.1 77 1968 TIANNLTSTIQVFT X AAO88201.1 78 1969 TQYSTGQVSVEIEW X AAO88201.1 79 1970 VTQNEGTKTIANNL X AAO88201.1 80 1971 WLEDNLSEGIREWW X AAO88201.1 81 1972 YFGYSTPWGYFDFN X AAO88201.1 82 1973 LSRTQSTGGTQGTQ X AAS99285.1 83 1974 TQGTQQLLFSQAGP X AAS99285.1 84 1975 DAEFQERLKEDTSF X AAVLK03.L1251 85 1976 DDEEKFFPMHGNLI X AAVLK03.L1251 86 1977 DGHFHPSPLMGGFG X AAVLK03.L1251 87 1978 DSESVPDPQPLGEP X AAVLK03.L1251 88 1979 EEEIRTTNPVATEQ X AAVLK03.L1251 89 1980 EEIRTTNPVATEQY X AAVLK03.L1251 90 1981 FQERLKEDTSFGGN X AAVLK03.L1251 91 1982 GADGVGNSSGNWHC X AAVLK03.L1251 92 1983 GDSESVPDPQPLGE X AAVLK03.L1251 93 1984 GNGLDKGEPVNAAD X AAVLK03.L1251 94 1985 KKRPVDQSPQEPDS X AAVLK03.L1251 95 1986 KRPVDQSPQEPDSS X AAVLK03.L1251 96 1987 KSVNVDFTVDTNGV X AAVLK03.L1251 97 1988 LSKTANDNNNSNFP X AAVLK03.L1251 98 1989 MASHKDDEEKFFPM X AAVLK03.L1251 99 1990 NNFQFSYTFEDVPF X AAVLK03.L1251 100 1991 PVDQSPQEPDSSSG X AAVLK03.L1251 101 1992 PVPANPPTTFSPAK X AAVLK03.L1251 102 1993 QQRLSKTANDNNNS X AAVLK03.L1251 103 1994 QSSNTAPTTRTVND X AAVLK03.L1251 104 1995 SKTANDNNNSNFPW X AAVLK03.L125I 105 1996 SNYNKSVNVDFTVD X AAVLK03.L1251 106 1997 TTSGTTNQSRLLFS X AAVLK03.L1251 107 1998 VMITDEEEIRTTNP X AAVLK03.L1251 108 1999 APGKKRPVEHSPVE X AAV2i8 109 2000 FFPQSGVLIFGKQG X AAV2i8 110 2001 FGKQGSEKTNVDIE X AAV2i8 111 2002 HKDDEEKFFPQSGV X AAV2i8 112 2003 KGEPVNEADAAALE X AAV2i8 113 2004 NEADAAALEHDKAY X AAV2i8 114 2005 NPVATEQYGSVSTN X AAV2i8 115 2006 PQILIKNTPVPANP X AAV2i8 116 2007 QQRVSKTSADNNNS X AAV2i8 117 2008 QTGDADSVPDPQPL X AAV2i8 118 2009 ADPPTTFNQAKLAS X AAV-Rh74 119 2010 AGDNVDYSSVMLTS X AAV-Rh74 120 2011 KNTPVPADPPTTFN X AAV-Rh74 121 2012 KRVLEPLGLVESPV X AAV-Rh74 122 2013 PYLRYHADAEFQER X AAV-Rh74 123 2014 EEEIKTTNPVATES X ALU85156.1 124 2015 EFAWPGASSWALNG X ALU85156.1 125 2016 KSNNVEFAVNTEGV X ALU85156.1 126 2017 MNPGPAMASHKEGE X ALU85156.1 127 2018 PVPADPPTAFNKDK X ALU85156.1 128 2019 TVQVFTDSDYQLPY X ALU85156.1 129 2020 NLQAANLALGETTR X AOD99656.1 130 2021 GGQMATNNQSLALG X AOD99659.1 131 2022 MATNNQSLALGETT X AOD99659.1 132 2023 KKRILEPLGLVEEA X AAB95452.1 133 2024 ADPPTTFNQSKLNS X 3J1Q 134 2025 KSTSVDFAVNTEGV X 3J1Q 135 2026 LQRGNRQAATADVN X 3J1Q 136 2027 PVPADPPTTFNQSK X 3J1Q 137 2028 DDDDRFFPMHGNLI X QLI60567.1 138 2029 PEPADVFMIPQYGY X AAO88201.1 139 2030 DIYYQGPIWAKVPH X A9RAI0 140 2031 FEKVPFHSMYAHSQ X A9RAI0 141 2032 FSAARINSFLTQYS X A9RAI0 142 2033 HSQSLDRMMNPLLD X A9RAI0 143 2034 KKRILEPLGLVEEG X A9RAI0 144 2035 MVPQYGYCGVVTGK X A9RAI0 145 2036 NQTDRNAFYCLEYF X A9RAI0 146 2037 RDTDMFGQIADNNQ X A9RAI0 147 2038 RDWQRLINNNWGLR X A9RAI0 148 2039 TVQIFADSTYELPY X A9RAI0 149 2040 DIYYQGPIWAKIPH X 041855 150 2041 QIFADSSYELPYVM X 041855 151 2042 THSTLDGRWSALTP X 041855 152 2043 TVQIFADSSYELPY X 041855 153 2044 DKFFPMSGVMIFGK X 056137 154 2045 EEEIKATNPVATER X 056137 155 2046 EGADGVGNASGNWH X 056137 156 2047 LFNIQVKEVTTNDG X 056137 157 2048 QVKEVTTNDGVTTI X 056137 158 2049 RVSKTKTDNNNSNF X 056137 159 2050 SDSEYQLPYVLGSA X 056137 160 2051 HSQSLDRLMNPLLD X Q5Y9B2 161 2052 IEMRAAPGGNAVDA X Q5Y9B2 162 2053 KRLNFEEDTGAGDG X Q5Y9B2 163 2054 SQSLDRLMNPLLDQ X Q5Y9B2 164 2055 STGQVAVQIEWEIE X Q5Y9B2 165 2056 TTSANNLLFTSEEE X Q5Y9B2 166 2057 TTSGETLNQGNAAT X Q5Y9B2 167 2058 GESESVPDPQPIGE X Q5Y9B4 168 2059 GQTGESESVPDPQP X Q5Y9B4 169 2060 ANPGIAMATHKDDE X Q8JQF8 170 2061 EGASYQVPPQPNGM X Q9YIJ1 171 2062 EYRTTRPIGTRYLT X Q9YIJ1 172 2063 YNLQEIVPGSVWME X Q9YIJ1

Example 20: Further Screen for Anti-AAV Antibodies in Human Sera

[0433] By using a cumulative gliding average signal of all sera tested over 4 consecutively aligned peptide signals along the corresponding AAV sequences, 1948 linear peptides were derived from AAV vectors AAV1, AAV2, AAV5, AAV6, AAV8, AAV9 and AAVrh.10.

[0434] Detailed results are shown in Table 3 below. 63 top candidates with the strongest signals were assigned to group I corresponding to 3.2 % of all AAV peptides analyzed by gliding average signal along the AAV VP1 sequence. The peptides of group I as well as the 135 peptides with second strongest signals were assigned to group II corresponding to 10.1 % of all AAV peptides analyzed. Additional 82 peptides (assigned to group III) were derived from the top 200 ranked peptide signals of the present screen not covered by group I and II. In summary, groups I, II and III thus contain 280 linear peptides suitable (as basis for SADCs) to remove or to detect anti AAV antibodies, in particular antibodies directed against the AAV1, AAV2, AAV5, AAV6, AAV8, AAV9 and AAVrh.10 VP1 proteins.

Table 3

[0435] This table provides a separate compilation of suitable peptides covering stretches along the VP1 sequence of widely used AAV vectors including AAV1, AAV2, AAV5, AAV6, AAV8, AAV9 and AAVrh.10. Source given is either UniProt ID, GenBank ID, PDB ID or AAV strain name. The asterisk (*) indicates peptide sequences for which a SEQ ID NO has already been assigned in Table 1 above.

TABLE-US-00016 peptide # SEQ ID NO peptide group I group II group III source 1 ∗ ADPPTAFNKDKLNSF X X Q6JC40 2 2064 ADTMSAGGGGPLGDN X X Q9YIJ1 3 ∗ AEFQERLKEDTSFGG X X spP03135 4 2065 AKTAPGKKRPVEPSP X X Q8JQF8 5 ∗ APTGKRIDDHFPKRK X X Q9YIJ1 6 ∗ DKLNSFITQYSTGQV X X Q6JC40 7 2066 DVYLQGPIWAKIPET X X Q9YIJ1 8 ∗ EEEIKTTNPVATEEY X X Q8JQF8 9 ∗ EEEIKTTNPVATEQY X X AAO88201.1 10 ∗ EEEIRTTNPVATEQY X X spP03135 11 ∗ EEIKTTNPVATEQYG X X AAO88201.1 12 ∗ EIKTTNPVATEEYGI X X Q8JQF8 13 ∗ EIRTTNPVATEQYGS X X spP03135 14 ∗ ELKKENSKRWNPEIQ X X Q9YIJ1 15 ∗ EMEWELKKENSKRWN X X Q9YIJ1 16 ∗ ERDVYLQGPIWAKIP X X Q9YIJ1 17 ∗ ERLKEDTSFGGNLGR X X spP03135 18 ∗ EWELKKENSKRWNPE X X Q9YIJ1 19 ∗ FITQYSTGQVSVEIE X X spP03135 20 ∗ FITQYSTGQVTVEME X X Q9YIJ1 21 ∗ FQERLKEDTSFGGNL X X spP03135 22 2067 GAKTAPTGKRIDDHF X X Q9YIJ1 23 2068 GQVATNHQSAQAQAQ X X Q6JC40 24 ∗ IKTTNPVATEQYGVV X X AAO88201.1 25 ∗ IQYTSNYNKSVNVDF X X spP03135 26 ∗ KKENSKRWNPEIQYT X X Q9YIJ1 27 ∗ KLNSFITQYSTGQVS X X Q6JC40 28 2069 KTAPTGKRIDDHFPK X X Q9YIJ1 29 ∗ KTTNPVATEEYGIVA X X Q8JQF8 30 ∗ LKEDTSFGGNLGRAV X X spP03135 31 ∗ LNSFITQYSTGQVSV X X Q6JC40 32 2070 MNPLIDQYLYYLSKT X X Q6JC40 33 2071 NHQYREIKSGSVDGS X X Q9YIJ1 34 ∗ NSFITQYSTGQVSVE X X Q6JC40 35 ∗ NTEGVYSEPRPIGTR X X Q6JC40 36 ∗ PADPPTAFNKDKLNS X X Q6JC40 37 ∗ PEIQYTSNYNKSVNV X X spP03135 38 ∗ PLIDQYLYYLSKTIN X X Q6JC40 39 2072 PTTFNQSKLNSFITQ X X Q8JQF8 40 ∗ PVPADPPTAFNKDKL X X Q6JC40 41 ∗ QGPIWAKIPETGAHF X X Q9YIJ1 42 2073 QYREIKSGSVDGSNA X X Q9YIJ1 43 ∗ REIKSGSVDGSNANA X X Q9YIJ1 44 ∗ RTTNPVATEQYGSVS X X spP03135 45 ∗ SEEEIKTTNPVATEQ X X AAO88201.1 46 ∗ SFITQYSTGQVSVEI X X spP03135 47 ∗ SSFITQYSTGQVTVE X X Q9YIJ1 48 ∗ SSVMLTSEEEIKTTN X X AAO88201.1 49 ∗ SSYAHSQSLDRLMNP X X spP03135 50 ∗ SVMLTSEEEIKTTNP X X AAO88201.1 51 2074 SYAHSQSLDRLMNPL X X spP03135 52 ∗ TMSAGGGGPLGDNNQ X X Q9YIJ1 53 ∗ TNPVATEEYGIVADN X X Q8JQF8 54 ∗ TNPVATEQYGSVSTN X X spP03135 55 ∗ TQTTGGTANTQTLGF X X Q8JQF8 56 ∗ TTNPVATEQYGVVAD X X AAO88201.1 57 ∗ VPADPPTAFNKDKLN X X Q6JC40 58 2075 VYSEPRPIGTRYLTR X X spP03135 59 ∗ WNPEIQYTSNYNKSV X X spP03135 60 2076 YLQGPIWAKIPETGA X X Q9YIJ1 61 ∗ YNNHQYREIKSGSVD X X Q9YIJ1 62 ∗ YSSVMLTSEEEIKTT X X AAO88201.1 63 ∗ YTSNYNKSVNVDFTV X X spP03135 64 ∗ ADAEFQERLKEDTSF X spP03135 65 ∗ AGPPKPKPNQQHQDQ X Q9YIJ1 66 ∗ AGPSGLGSGTMAAGG X AAO88201.1 67 ∗ ANNLTSTVQVFTDDD X Q9YIJ1 68 ∗ CYRQQRVSTTTGQNN X Q8JQF8 69 ∗ DPPTTFNQSKLNSFI X Q8JQF8 70 2077 DSSSGTGKAGQQPAR X spP03135 71 ∗ DSTTTIANNLTSTVQ X Q9YIJ1 72 ∗ EDTSFGGNLGRAVFQ X spP03135 73 ∗ EEGAKTAPGKKRPVE X Q8JQF8 74 ∗ EEGAKTAPTGKRIDD X Q9YIJ1 75 ∗ EEIKTTNPVATESYG X Q6JC40 76 ∗ EFENVPFHSSYAHSQ X Q6JC40 77 ∗ EGAKTAPGKKRPVEP X Q8JQF8 78 ∗ EGLREFLGLEAGPPK X Q9YIJ1 79 ∗ EIQYTSNYYKSTNVD X AAO88201.1 80 ∗ EKTNVDIEKVMITDE X spP03135 81 ∗ ELQKENSKRWNPEIQ X spP03135 82 ∗ ENSKRWNPEIQYTNN X Q9YIJ1 83 ∗ ENVPFHSSYAHSQSL X Q6JC40 84 ∗ EPDSSSGTGKAGQQP X spP03135 85 ∗ EQLEAGDNPYLKYNH X Q9YIJ1 86 ∗ EWELQKENSKRWNPE X spP03135 87 ∗ GAKTAPGKKRPVEPS X Q8JQF8 88 ∗ GEPPAGPSGLGSGTM X AAO88201.1 89 ∗ GGTANTQTLGFSQGG X Q8JQF8 90 ∗ GSEKTNVDIEKVMIT X spP03135 91 2078 GVVADNLQQQNAAPI X AAO88201.1 92 ∗ GVYSEPRPIGTRYLT X spP03135 93 2079 HSSFAPSQNLFKLAN X Q9YIJ1 94 ∗ HSSYAHSQSLDRLMN X spP03135 95 ∗ IKNTPVPADPPTAFN X Q6JC40 96 ∗ IKTTNPVATESYGQV X Q6JC40 97 ∗ ILIKNTPVPADPPTA X Q6JC40 98 ∗ IQYTSNYYKSNNVEF X Q6JC40 99 ∗ IQYTSNYYKSTNVDF X AAO88201.1 100 ∗ ITNEEEIKTTNPVAT X Q6JC40 101 ∗ ITQYSTGQVSVEIEW X spP03135 102 2080 KDKLNSFITQYSTGQ X Q6JC40 103 ∗ KNTPVPADPPTAFNK X Q6JC40 104 ∗ KRWNPEIQYTSNYNK X spP03135 105 2081 KRWNPEIQYTSNYYK X Q6JC40 106 2082 LEAGDNPYLKYNHAD X Q9YIJ1 107 ∗ LEAGPPKPKPNQQHQ X Q9YIJ1 108 ∗ LGADTMSAGGGGPLG X Q9YIJ1 109 ∗ LGLEAGPPKPKPNQQ X Q9YIJ1 110 ∗ LIKNTPVPADPPTAF X Q6JC40 111 2083 LKYNHADAEFQEKLA X Q9YIJ1 112 ∗ LQKENSKRWNPEIQY X spP03135 113 ∗ LREFLGLEAGPPKPK X Q9YIJ1 114 ∗ LYYLSRTNTPSGTTT X spP03135 115 ∗ NEEEIKTTNPVATES X Q6JC40 116 ∗ NKDKLNSFITQYSTG X Q6JC40 117 ∗ NNSNFAWTAGTKYHL X Q8JQF8 118 ∗ NPVATEQYGVVADNL X AAO88201.1 119 ∗ NPVATESYGQVATNH X Q6JC40 120 2084 NSQGALPGMVWQNRD X Q8JQF8 121 ∗ NTPVPADPPTAFNKD X Q6JC40 122 ∗ NTPVPADPPTTFNQS X Q8JQF8 123 2085 PADPPTTFNQSKLNS X Q8JQF8 124 ∗ PFHSSFAPSQNLFKL X Q9YIJ1 125 ∗ PIGEPPAGPSGLGSG X AAO88201.1 126 2086 PPAGPSGLGSGTMAA X AAO88201.1 127 ∗ PQILIKNTPVPADPP X Q6JC40 128 ∗ PQYGYATLNRDNTEN X Q9YIJ1 129 ∗ PSTSSDAEAGPSGSQ X Q9YIJ1 130 ∗ PVATEQYGSVSTNLQ X spP03135 131 ∗ PVEPDSSSGTGKAGQ X spP03135 132 ∗ PVPADPPTTFNQSKL X Q8JQF8 133 ∗ PVPGNITSFSDVPVS X Q9YIJ1 134 2087 PYLKYNHADAEFQEK X Q9YIJ1 135 ∗ QILIKNTPVPADPPT X Q6JC40 136 ∗ QRVSTTTGQNNNSNF X Q8JQF8 137 2088 QSGASNDNHYFGYST X spP03135 138 2089 QSTGGTAGTQQLLFS X AAO88201.1 139 ∗ QVTVEMEWELKKENS X Q9YIJ1 140 2090 QYGVVADNLQQQNAA X AAO88201.1 141 ∗ QYTSNYYKSNNVEFA X Q6JC40 142 ∗ RQQRVSTTTGQNNNS X Q8JQF8 143 2091 RWNPEIQYTSNYYKS X Q6JC40 144 2092 SFAPSQNLFKLANPL X Q9YIJ1 145 ∗ SGNWHCDSTWLGDRV X Q8JQF8 146 2093 SKRWNPEIQYTSNYY X Q6JC40 147 ∗ SNYNKSVNVDFTVDT X spP03135 148 2094 SQSGASNDNHYFGYS X spP03135 149 2095 SRTNTPSGTTTQSRL X spP03135 150 ∗ SSGNWHCDSTWLGDR X Q8JQF8 151 ∗ SSGTGKAGQQPARKR X spP03135 152 ∗ SSLGADTMSAGGGGP X Q9YIJ1 153 ∗ SSQSGASNDNHYFGY X spP03135 154 ∗ SSSGNWHCDSTWLGD X Q8JQF8 155 ∗ STGGTAGTQQLLFSQ X AAO88201.1 156 ∗ STTLSQNNNSNFAWT X AAO88201.1 157 2096 SYGQVATNHQSAQAQ X Q6JC40 158 2097 TANTQTLGFSQGGPN X Q8JQF8 159 ∗ TEGVYSEPRPIGTRY X Q6JC40 160 2098 TEQYGVVADNLQQQN X AAO88201.1 161 ∗ TESYGQVATNHQSAQ X Q6JC40 162 ∗ TGGTAGTQQLLFSQA X AAO88201.1 163 2099 TGQNNNSNFAWTAGT X Q8JQF8 164 ∗ TLNRDNTENPTERSS X Q9YIJ1 165 ∗ TLSQNNNSNFAWTGA X AAO88201.1 166 ∗ TNGVYSEPRPIGTRY X spP03135 167 ∗ TNTPSGTTTQSRLQF X spP03135 168 ∗ TNVDIEKVMITDEEE X spP03135 169 ∗ TQSTGGTAGTQQLLF X AAO88201.1 170 ∗ TQYSTGQVSVEIEWE X spP03135 171 ∗ TQYSTGQVTVEMEWE X Q9YIJ1 172 ∗ TSNYYKSNNVEFAVN X Q6JC40 173 ∗ TSSDAEAGPSGSQQL X Q9YIJ1 174 ∗ TTGGTANTQTLGFSQ X Q8JQF8 175 ∗ TTLSQNNNSNFAWTG X AAO88201.1 176 2100 TTNPVATESYGQVAT X Q6JC40 177 ∗ TTTGQNNNSNFAWTA X Q8JQF8 178 ∗ TVEMEWELKKENSKR X Q9YIJ1 179 ∗ VATEQYGWADNLQQ X AAO88201.1 180 ∗ VATESYGQVATNHQS X Q6JC40 181 ∗ VATNHQSAQAQAQTG X Q6JC40 182 ∗ VDIEKVMITDEEEIR X spP03135 183 ∗ VDTNGVYSEPRPIGT X spP03135 184 ∗ VEIEWELQKENSKRW X spP03135 185 ∗ VNTEGVYSEPRPIGT X Q6JC40 186 ∗ VQDSTTTIANNLTST X Q9YIJ1 187 ∗ VSTTLSQNNNSNFAW X AAO88201.1 188 ∗ VSTTTGQNNNSNFAW X Q8JQF8 189 ∗ VTVQDSTTTIANNLT X Q9YIJ1 190 2101 WTGATKYHLNGRDSL X spP03135 191 2102 YAHSQSLDRLMNPLI X spP03135 192 ∗ YATLNRDNTENPTER X Q9YIJ1 193 * YGYATLNRDNTENPT X Q9YIJ1 194 ∗ YLSRTNTPSGTTTQS X spP03135 195 ∗ YNKSVNVDFTVDTNG X spP03135 196 ∗ YNNHLYKQISNGTSG X Q8JQF8 197 ∗ YSTGQVTVEMEWELK X Q9YIJ1 198 2103 YTSNYYKSNNVEFAV X Q6JC40 199 ∗ ASHKDDEEKFFPQSG X spP03135 200 ∗ ASNDNHYFGYSTPWG X spP03135 201 ∗ ATERFGTVAVNLQSS X 056137 202 ∗ AVNLQSSSTDPATGD X 056137 203 ∗ DAAALEHDKAYDQQL X Q6JC40 204 ∗ DAEFQERLQEDTSFG X Q8JQF8 205 ∗ DDEEKFFPQSGVLIF X spP03135 206 ∗ EDSKPSTSSDAEAGP X Q9YIJ1 207 ∗ EDVPFHSSYAHSQSL X spP03135 208 ∗ EEEIKATNPVATERF X Q9WBP8 209 ∗ EEVGEGLREFLGLEA X Q9YIJ1 210 ∗ EEYGIVADNLQQQNT X Q8JQF8 211 ∗ EFLGLEAGPPKPKPN X Q9YIJ1 212 ∗ EHDKAYDQQLKAGDN X Q6JC40 213 ∗ EHDKAYDRQLDSGDN X spP03135 214 ∗ EIKATNPVATERFGT X Q9WBP8 215 ∗ EPDSSAGIGKSGAQP X Q6JC40 216 ∗ EPVNAADAAALEHDK X Q6JC40 217 ∗ EPVNEADAAALEHDK X spP03135 218 ∗ ERHKDDSRGLVLPGY X spP03135 219 ∗ ESVPDPQPIGEPPAA X Q6JC40 220 ∗ EVPFHSSFAPSQNLF X Q9YIJ1 221 ∗ FHSSYAHSQSLDRLM X spP03135 222 ∗ FNGLDKGEPVNAADA X Q8JQF8 223 ∗ FNGLDKGEPVNEADA X spP03135 224 ∗ GEPVNAADAAALEHD X Q6JC40 225 ∗ GEPVNEADAAALEHD X spP03135 226 ∗ GNGLDKGEPVNAADA X Q6JC40 227 ∗ GSAHQGCLPPFPADV X spP03135 228 ∗ GSSSGNWHCDSTWLG X Q8JQF8 229 ∗ IGTVNSQGALPGMVW X Q8JQF8 230 ∗ IQVKEVTTNDGVTTI X Q9WBP8 231 ∗ LIKNTPVPADPPTTF X Q8JQF8 232 ∗ LRTGNNFEFSYQFED X AAO88201.1 233 ∗ NEADAAALEHDKAYD X spP03135 234 ∗ NNNSEFAWPGASSWA X Q6JC40 235 ∗ NNSEYSWTGATKYHL X spP03135 236 ∗ NVGGQMATNNQSSTT X Q9YIJ1 237 ∗ NYNDPQFVDFAPDST X Q9YIJ1 238 ∗ PLGEPPATPAAVGPT X Q9WBP8 239 ∗ PQPLGEPPATPAAVG X Q9WBP8 240 ∗ PSKMLRTGNNFEFTY X Q9YIJ1 241 ∗ PVATEEYGIVADNLQ X Q8JQF8 242 ∗ PVEPSPQRSPDSSTG X Q8JQF8 243 ∗ PVEQSPQEPDSSSGI X Q9WBP8 244 ∗ PVNEADAAALEHDKA X spP03135 245 ∗ PVPANPPAEFSATKF X Q9WBP8 246 ∗ QQRVSTTLSQNNNSN X AAO88201.1 247 ∗ QRVSKTKTDNNNSNF X Q9WBP8 248 ∗ QRVSTTLSQNNNSNF X AAO88201.1 249 ∗ QSSSTDPATGDVHVM X 056137 250 ∗ QYTNNYNDPQFVDFA X Q9YIJ1 251 ∗ RVSTTLSQNNNSNFA X AAO88201.1 252 ∗ SDSEYQLPYVLGSAH X Q9WBP8 253 ∗ SESVPDPQPIGEPPA X AAO88201.1 254 ∗ SESVPDPQPLGEPPA X Q8JQF8 255 ∗ SFVDHPPDWLEEVGE X Q9YIJ1 256 ∗ SSNDNAYFGYSTPWG X Q6JC40 257 ∗ SSSGIGKTGQQPAKK X Q9WBP8 258 ∗ STTVTQNNNSEFAWP X Q6JC40 259 ∗ SVPDPQPLGEPPAAP X Q8JQF8 260 ∗ SVPDPQPLGEPPATP X Q9WBP8 261 ∗ SYEFENVPFHSSYAH X Q6JC40 262 ∗ SYTFEDVPFHSSYAH X spP03135 263 ∗ TDEEEIKATNPVATE X Q9WBP8 264 ∗ TDEEEIRTTNPVATE X spP03135 265 ∗ TGNNFEFSYQFEDVP X AAO88201.1 266 ∗ TMATGSGAPMADNNE X spP03135 267 ∗ TNNYNDPQFVDFAPD X Q9YIJ1 268 ∗ TNTMATGSGAPMADN X spP03135 269 ∗ TPVPADPPTAFNKDK X Q6JC40 270 ∗ TPVPADPPTTFSQAK X AAO88201.1 271 ∗ TSTVQVFTDSEYQLP X spP03135 272 ∗ TSVDFAVNTEGVYSE X Q8JQF8 273 ∗ TVAVNLQSSSTDPAT X 056137 274 ∗ VDFAVNTEGVYSEPR X Q8JQF8 275 ∗ VEFAVNTEGVYSEPR X Q6JC40 276 ∗ VLEPLGLVEEGAKTA X Q8JQF8 277 ∗ VNVDFTVDTNGVYSE X spP03135 278 ∗ VSVEIEWELQKENSK X spP03135 279 ∗ WLEDNLSEGIREWWD X Q9WBP8 280 ∗ YNEQLEAGDNPYLKY X Q9YIJ1

Example 21: Further Screen for Anti-Vector Antibodies in Human Sera

[0436] Out of the 3285 cyclic peptides derived from Ad5 Hexon, fiber and penton proteins P04133, P11818 and P12538, respectively, and AAV VP1 sequences P03135, Q6JC40, Q8JQF8, Q9WBP8, Q9YIJ1, 056137, AAO88201.1, 041855, O56139 and Q8JQG0, the peptides with the top 5% maximal IgG signal strength over the microarray screens were obtained, yielding a total of 164 peptides with top signals from the vector protein sequences screened. The details are shown in Table 4 below.

Table 4

[0437] This table provides another compilation of viral peptide sequences suitable as a basis for the present invention. Source given is either UniProt ID or GenBank ID. The asterisk (*) indicates peptide sequences for which a SEQ ID NO has already been assigned in Table 2 above.

TABLE-US-00017 peptide # SEQ ID NO peptide source 1 2104 AAEAAAPAAQPEVE P12538 2 2105 AAAPAAQPEVEKPQ P12538 3 2106 DASEYLSPGLVQFA P04133 4 2107 DGLEFGSPNAPNTN P11818 5 2108 APVAAALGSPFDAP P12538 6 2109 NLEEEDDDNEDEVD P04133 7 2110 EEDDDNEDEVDEQA P04133 8 2111 DDNEDEVDEQAEQQ P04133 9 2112 VLQSSLGNDLRVDG P04133 10 2113 PSEDTFNPVYPYDT P11818 11 2114 FPVVGAELLPVHSK P12538 12 2115 EEIRPTNPVATEEY Q8JQG0 13 2116 SGSGAEENSNAAAA P12538 14 2117 YEEGPPPSYESVVS P12538 15 2118 NAAAAAMQPVEDMN P12538 16 2119 AAALGSPFDAPLDP P12538 17 2120 NGVLESDIGVKFDT P12538 18 2121 AAAMQPVEDMNDHA P12538 19 2122 PAQPASSLGADTMS Q9YIJ1 20 2123 TVQVFTDDDYQLPY Q9YIJ1 21 2124 PVPGNITSFSDVPV Q9YIJ1 22 2125 TQYSTGQVTVEMEW Q9YIJ1 23 2126 YLGPGNGLDRGEPV Q9YIJ1 24 2127 TSESETQPVNRVAY Q9YIJ1 25 2128 RARPSEDTFNPVYP P11818 26 2129 ATALEINLEEEDDD P04133 27 2130 ENSNAAAAAMQPVE P12538 28 2131 YLGPFNGLDKGEPV P03135 29 2132 NNFEFSYSFEDVPF Q8JQG0 30 2133 SFITQYSTGQVTVE Q9YIJ1 31 2134 YNKSVNVDFTVDTN P03135 32 2135 LGSPFDAPLDPPFV P12538 33 2136 PAAQPEVEKPQKKP P12538 34 2137 ENSKRWNPEIQYTN Q9YIJ1 35 2138 YLVDNKSTDVASLN P12538 36 2139 PPMMLIKNTPVPGN Q9YIJ1 37 2140 PVPADPPTTFSQAK AAO88201.1 38 2141 DTFNPVYPYDTETG P11818 39 2142 ITQYSTGQVTVEME Q9YIJ1 40 2143 AGNLTSQNVTTVSP P11818 41 2144 NNFTFSYTFEDVPF P03135 42 2145 WVLPSYNNHQYREI Q9YIJ1 43 2146 YLGPGNGLDKGEPV Q6JC40 44 2147 FLYSNIALYLPDKL P04133 45 2148 NSTGNMGVLAGQAS P04133 46 2149 YLKYNHADAEFQER P03135 47 2150 LAPKGAPNPCEWDE P04133 48 2151 IQYTNNYNDPQFVD Q9YIJ1 49 2152 SHGKTAKSNIVSQV P11818 50 2153 VSAAPVAAALGSPF P12538 51 2154 GNDRLLTPNEFEIK P04133 52 2155 LEINLEEEDDDNED P04133 53 2156 YLRYNHADAEFQER Q8JQF8 54 2157 AAGGAAVEGGQGAD 041855 55 2158 VKEVTTSNGETTVA 041855 56 2159 EAMLRNDTNDQSFN P04133 57 2160 DGHFHPSPLIGGFG 041855 58 2161 NMTKDWFLVQMLAN P04133 59 2162 VGSGTVAAGGGAPM Q8JQG0 60 2163 EQYGTVANNLQSSN 056139 61 2164 CLEYFPSKMLRTGN Q9YIJ1 62 2165 AHALDMTFEVDPMD P04133 63 2166 TMANQAKNWLPGPC Q8JQF8 64 2167 KRPVEQSPQEPDSS Q6JC40 65 2168 KTANDNNNSNFPWT 056139 66 2169 TQNNNSEFAWPGAS Q6JC40 67 2170 KNTPVPADPPTAFN Q6JC40 68 2171 TVQVFSDSEYQLPY Q9WBP8 69 2172 LDKGEPVNAADAAA Q6JC40 70 2173 VLEPLGLVEEPVKT P03135 71 2174 KLFNIQVKEVTTND Q9WBP8 72 2175 LQSSNTAPTTRTVN 056139 73 2176 SPPLKKTKSNINLE P11818 74 2177 LDKGEPVNEADAAA P03135 75 2178 MLRTGNNFQFSYEF Q6JC40 76 2179 ARKRLNFGQTGDAD P03135 77 2180 NTYNGFSTPWGYFD 041855 78 2181 QYGTVANNLQSSNT 056139 79 2182 LARPPAPTITTVSE P12538 80 2183 FPADVFMIPQYGYL Q6JC40 81 2184 STGQVSVEIEWELQ P03135 82 2185 LRNDTNDQSFNDYL P04133 83 2186 NFQFSYEFENVPFH Q6JC40 84 2187 FITQYSTGQVTVEM Q9YIJ1 85 2188 QQPARKRLNFGQTG P03135 86 2189 HDSKLSIATQGPLT P11818 87 2190 NTYFGYSTPWGYFD Q8JQF8 88 * ANNLTSTVQIFADS 041855 89 * GNTSQQQTDRNAFY 041855 90 * DTNGVYSEPRPIGT P03135 91 * KIFNIQVKEVTTSN 041855 92 * LIKNTPVPADPPTT Q8JQF8 93 * DEEEIRTTNPVATE P03135 94 * DKAYDRQLDSGDNP P03135 95 * DKDKFFPMSGVMIF 056137 96 * LQQQNTAPQIGTVN Q8JQF8 97 * GTNTMATGSGAPMA P03135 98 * IFNIQVKEVTTSNG 041855 99 * DKAYDQQLQAGDNP Q8JQF8 100 * DSQWLGDRVITTST Q6JC40 101 * DEEEIKATNPVATE Q9WBP8 102 * SFITQYSTGQVSVE P03135 103 * PLVDQYLYRFVSTN Q9YIJ1 104 * GKKRPVDQSPQEPD 056139 105 * NPVATEQYGSVSTN P03135 106 * DKAYDQQLKAGDNP Q6JC40 107 * TAPGKKRPVDQSPQ 056139 108 * VMITDEEEIRTTNP P03135 109 * FGKQGSEKTNVDIE P03135 110 * LQRGNRQAATADVN P03135 111 * KTAPGKKRPVDQSP 056139 112 * SESVPDPQPIGEPP AAO88201.1 113 * LEDNLSEGIREWWD Q9WBP8 114 * PEIQYTSNYNKSVN P03135 115 * DKFFPMSGVMIFGK Q9WBP8 116 * APGKKRPVDQSPQE 056139 117 * NNFQFSYTFEDVPF 056139 118 * EFAWPGASSWALNG Q6JC40 119 * QSSNTAPTTRTVND 056139 120 * PVPADPPTTFNQSK Q8JQF8 121 * TQYSTGQVSVEIEW P03135 122 * SKTANDNNNSNFPW 056139 123 * TVQIFADSSYELPY 041855 124 * SESVPDPQPLGEPP Q8JQF8 125 * TESVPDPQPIGEPP Q6JC40 126 * KNTPVPADPPTTFS AAO88201.1 127 * PVPADPPTAFNKDK Q6JC40 128 * KKRPVDQSPQEPDS 056139 129 * KNTPVPADPPTTFN Q8JQF8 130 * PRDWQRLINNNWGF P03135 131 * LFNIQVKEVTTNDG Q9WBP8 132 * TTSGTTNQSRLLFS 056139 133 * LSKTANDNNNSNFP 056139 134 * ENSKRWNPEIQYTS P03135 135 * DIYYQGPIWAKIPH 041855 136 * DDEDKFFPMSGVMI Q9WBP8 137 * THSTLDGRWSALTP 041855 138 * GADGVGNSSGNWHC P03135 139 * TIANNLTSTIQVFT Q8JQF8 140 * PQILIKNTPVPADP Q6JC40 141 * QLKAGDNPYLRYNH Q9WBP8 142 * NYNKSVNVDFTVDT P03135 143 * EEEIKTTNPVATEE Q8JQF8 144 * KGEPVNEADAAALE P03135 145 * KGEPVNAADAAALE Q6JC40 146 * DGHFHPSPLMGGFG P03135 147 * HYFGYSTPWGYFDF P03135 148 * EEIKTTNPVATEQY AAO88201.1 149 * FNIQVKEVTTNDGV Q9WBP8 150 * PWGYFDFNRFHCHF P03135 151 * LQQQNAAPIVGAVN AAO88201.1 152 * DWLEDNLSEGIREW Q6JC40 153 * WLEDNLSEGIREWW Q6JC40 154 * DSESVPDPQPIGEP AAO88201.1 155 * KRPVDQSPQEPDSS 056139 156 * HSQSLDRLMNPLID P03135 157 * FEKVPFHSMYAHSQ 041855 158 * YDQQLKAGDNPYLK Q6JC40 159 * EDNLSEGIREWWDL Q9WBP8 160 * QVKEVTTNDGVTTI Q9WBP8 161 * PQYGYLTLNNGSQA P03135 162 * EEEIKTTNPVATES Q6JC40 163 * EGADGVGNASGNWH Q9WBP8 164 * DSESVPDPQPLGEP Q8JQF8

NON-PATENT REFERENCES

[0438] Balakrishnan, Balaji, and Ernest David. “Biopolymers augment viral vectors based gene delivery.” Journal of biosciences 44.4 (2019): 1-8.

[0439] Bennett, Antonette, et al. “Structure comparison of the chimeric AAV2. 7m8 vector with parental AAV2.” Journal of structural biology 209.2 (2020): 107433.

[0440] Bertin, Berangere, et al. “Capsid-specific removal of circulating antibodies to adeno-associated virus vectors.” Scientific reports 10.1 (2020): 1-11.

[0441] Börner, Kathleen, et al. “Pre-arrayed pan-AAV peptide display libraries for rapid single-round screening.” Molecular Therapy 28.4 (2020): 1016-1032.

[0442] Carter, John Mark, and Larry Loomis-Price. “B cell epitope mapping using synthetic peptides.” Current protocols in immunology 60.1 (2004): 9-4.

[0443] Cearley, Cassia N., et al. “Expanded repertoire of AAV vector serotypes mediate unique patterns of transduction in mouse brain.” Molecular therapy 16.10 (2008): 1710-1718.

[0444] Colella, Pasqualina, Giuseppe Ronzitti, and Federico Mingozzi. “Emerging issues in AAV-mediated in vivo gene therapy.” Molecular Therapy-Methods & Clinical Development 8 (2018): 87-104.

[0445] Dijkstra, C. D., et al. “The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in rat recognized by monoclonal antibodies ED1, ED2 and ED3.” Microenvironments in the Lymphoid System. Springer, Boston, MA, 1985. 409-419.

[0446] Domenger, Claire, and Dirk Grimm. “Next-generation AAV vectors-do not judge a virus (only) by its cover.” Human molecular genetics 28.R1 (2019): R3-R14.

[0447] Elliott, Serra E., et al. “A pre-eclampsia-associated Epstein-Barr virus antibody cross-reacts with placental GPR50.” Clinical Immunology 168 (2016): 64-71.

[0448] Erlandsson, Ann, et al. “In vivo clearing of idiotypic antibodies with antiidiotypic antibodies and their derivatives.” Molecular immunology 43.6 (2006): 599-606.

[0449] Etzerodt, Anders, et al. “Efficient intracellular drug-targeting of macrophages using stealth liposomes directed to the hemoglobin scavenger receptor CD163.” Journal of controlled release 160.1 (2012): 72-80.

[0450] Fabriek, Babs O., et al. “The macrophage scavenger receptor CD163 functions as an innate immune sensor for bacteria.” Blood 113.4 (2009): 887-892.

[0451] Fausther-Bovendo, Hugues, and Gary P. Kobinger. “Preexisting immunity against Ad vectors: humoral, cellular, and innate response, what’s important?.” Human vaccines & immunotherapeutics 10.10 (2014): 2875-2884.

[0452] Garces, Jorge Carlos, et al. “Antibody-mediated rejection: a review.” The Ochsner Journal 17.1 (2017): 46.

[0453] Gazarian, Karlen, et al. “Mimotope peptides selected from phage display combinatorial library by serum antibodies of pigs experimentally infected with Taenia solium as leads to developing diagnostic antigens for human neurocysticercosis.” Peptides 38.2 (2012): 381-388.

[0454] Gfeller, David, et al. “Current tools for predicting cancer-specific T cell immunity.” Oncoimmunology 5.7 (2016): e1177691.

[0455] Granfeldt, Asger, et al. “Targeting dexamethasone to macrophages in a porcine endotoxemic model.” Critical Care Medicine 41.11 (2013): e309-e318.

[0456] Graversen, Jonas H., et al. “Targeting the hemoglobin scavenger receptor CD163 in macrophages highly increases the anti-inflammatory potency of dexamethasone.” Molecular Therapy 20.8 (2012): 1550-1558.

[0457] Gurda, Brittney L., et al. “Mapping a neutralizing epitope onto the capsid of adeno-associated virus serotype 8.” Journal of virology 86.15 (2012): 7739-7751.

[0458] Hansen, Lajla Bruntse, Soren Buus, and Claus Schafer-Nielsen. “Identification and mapping of linear antibody epitopes in human serum albumin using high-density peptide arrays.” PLoS One 8.7 (2013): e68902.

[0459] Homma, Masayuki, et al. “A Novel Fusion Protein, AChR-Fc, Ameliorates Myasthenia Gravis by Neutralizing Antiacetylcholine Receptor Antibodies and Suppressing Acetylcholine Receptor-Reactive B Cells.” Neurotherapeutics 14.1 (2017): 191-198.

[0460] Howard Jr, James F. “Myasthenia gravis: the role of complement at the neuromuscular junction.” Annals of the New York Academy of Sciences 1412.1 (2018): 113-128.

[0461] Howarth, M., & Brune, K. D. (2018). New routes and opportunities for modular construction of particulate vaccines: stick, click and glue. Frontiers in immunology, 9, 1432.

[0462] Jansson, Liselotte, et al. “Immunotherapy With Apitopes Blocks the Immune Response to TSH Receptor in HLA-DR Transgenic Mice.” Endocrinology 159.9 (2018): 3446-3457.

[0463] Jensen, Kamilla Kjærgaard, et al. “Improved methods for predicting peptide binding affinity to MHC class II molecules.” Immunology 154.3 (2018): 394-406.

[0464] Jurtz, Vanessa, et al. “NetMHCpan-4.0: improved peptide-MHC class I interaction predictions integrating eluted ligand and peptide binding affinity data.” The Journal of Immunology 199.9 (2017): 3360-3368.

[0465] Kainulainen, Markus H., et al. “High-throughput quantitation of SARS-CoV-2 antibodies in a single-dilution homogeneous assay.” Scientific reports 11.1 (2021): 1-9.

[0466] Koşaloğlu-Yalçin, Zeynep, et al. “Predicting T cell recognition of MHC class I restricted neoepitopes.” Oncoimmunology 7.11 (2018): e1492508.

[0467] Krasnykh, Victor, et al. “Characterization of an adenovirus vector containing a heterologous peptide epitope in the HI loop of the fiber knob.” Journal of virology 72.3 (1998): 1844-1852.

[0468] Kruzik, Anita, et al. “Prevalence of anti-adeno-associated virus immune responses in international cohorts of healthy donors.” Molecular Therapy-Methods & Clinical Development 14 (2019): 126-133.

[0469] Lazaridis, Konstantinos, et al. “Specific removal of autoantibodies by extracorporeal immunoadsorption ameliorates experimental autoimmune myasthenia gravis.” Journal of neuroimmunology 312 (2017): 24-30.

[0470] Leung, Nicki YH, et al. “Screening and identification of mimotopes of the major shrimp allergen tropomyosin using onebead-one-compound peptide libraries.” Cellular & molecular immunology 14.3 (2017): 308-318.

[0471] Li, Chengwen, and R. Jude Samulski. “Engineering adeno-associated virus vectors for gene therapy.” Nature Reviews Genetics 21.4 (2020): 255-272.

[0472] Li, Peipei, Li Wang, and Li-jun Di. “Applications of protein fragment complementation assays for analyzing biomolecular interactions and biochemical networks in living cells.” Journal of proteome research 18.8 (2019): 2987-2998.

[0473] Lim, Sung In, and Inchan Kwon. “Bioconjugation of therapeutic proteins and enzymes using the expanded set of genetically encoded amino acids.” Critical reviews in biotechnology 36.5 (2016): 803-815.

[0474] Lin, Chia-Hao, et al. “Identification of a major epitope by anti-interferon-γ autoantibodies in patients with mycobacterial disease.” Nature medicine 22.9 (2016): 994.

[0475] Lorentz, Kristen M., et al. “Engineered binding to erythrocytes induces immunological tolerance to E. coli asparaginase.” Science advances 1.6 (2015): e1500112.

[0476] Luo, Jie, et al. “Main immunogenic region structure promotes binding of conformation-dependent myasthenia gravis autoantibodies, nicotinic acetylcholine receptor conformation maturation, and agonist sensitivity.” Journal of Neuroscience 29.44 (2009): 13898-13908.

[0477] Luo, Jie, and Jon Lindstrom. “AChR-specific immunosuppressive therapy of myasthenia gravis.” Biochemical pharmacology 97.4 (2015): 609-619.

[0478] Madsen, Mette, et al. “Molecular Characterization of the Haptoglobin.Math. Hemoglobin Receptor CD163 ligand binding properties of the scavenger receptor cysteine-rich domain region.” Journal of Biological Chemistry 279.49 (2004): 51561-51567.

[0479] Majowicz, Anna, et al. “Seroprevalence of pre-existing NABs against AAV1, 2, 5, 6 and 8 in the South African Hemophilia B patient population.” (2019): 3353-3353.

[0480] Manno, Catherine S., et al. “Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response.” Nature medicine 12.3 (2006): 342-347.

[0481] Mazor, Ronit, et al. “Tolerogenic nanoparticles restore the antitumor activity of recombinant immunotoxins by mitigating immunogenicity.” Proceedings of the National Academy of Sciences 115.4 (2018): E733-E742.

[0482] Meister, Daniel, S. Maryamdokht Taimoory, and John F. Trant. “Unnatural amino acids improve affinity and modulate immunogenicity: Developing peptides to treat MHC type II autoimmune disorders.” Peptide Science 111.1 (2019): e24058.

[0483] Mietzsch, Mario, et al. “OneBac: platform for scalable and high-titer production of adeno-associated virus serotype 1-12 vectors for gene therapy.” Human gene therapy 25.3 (2014): 212-222.

[0484] Mimuro, Jun, et al. “Minimizing the inhibitory effect of neutralizing antibody for efficient gene expression in the liver with adeno-associated virus 8 vectors.” Molecular Therapy 21.2 (2013): 318-323.

[0485] Mingozzi, Federico, et al. “Overcoming preexisting humoral immunity to AAV using capsid decoys.” Science translational medicine 5.194 (2013): 194ra92-194ra92.

[0486] Mingozzi, Federico, and Katherine A. High. “Overcoming the host immune response to adeno-associated virus gene delivery vectors: the race between clearance, tolerance, neutralization, and escape.” Annual review of virology 4 (2017): 511-534.

[0487] Mok, Darren ZL, and Kuan Rong Chan. “The effects of preexisting antibodies on live-attenuated viral vaccines.” Viruses 12.5 (2020): 520.

[0488] Monahan, Paul E., et al. “Emerging Immunogenicity and Genotoxicity Considerations of Adeno-Associated Virus Vector Gene Therapy for Hemophilia.” Journal of Clinical Medicine 10.11 (2021): 2471.

[0489] Morimoto et. al., Bioconjugate Chemistry 25 (8) (2014): 1479-1491

[0490] Moussa, Ehab M., et al. “Immunogenicity of therapeutic protein aggregates.” Journal of pharmaceutical sciences 105.2 (2016): 417-430.

[0491] Müller, Manuel M. “Post-translational modifications of protein backbones: unique functions, mechanisms, and challenges.” Biochemistry 57.2 (2017): 177-185.

[0492] Siang Ong, Yong, et al. “Recent advances in synthesis and identification of cyclic peptides for bioapplications.” Current topics in medicinal chemistry 17.20 (2017): 2302-2318.

[0493] Peters, Bjoern, et al. “A community resource benchmarking predictions of peptide binding to MHC-I molecules.” PLoS computational biology 2.6 (2006): e65.

[0494] Pishesha, Novalia, et al. “Engineered erythrocytes covalently linked to antigenic peptides can protect against autoimmune disease.” Proceedings of the National Academy of Sciences (2017): 201701746.

[0495] Rey et al., Clinical Immunology 96 (3) (2000): 269-279

[0496] Rice, Peter, Ian Longden, and Alan Bleasby. “EMBOSS: the European molecular biology open software suite.” Trends in genetics 16.6 (2000): 276-277.

[0497] Roberts, Diane M., et al. “Hexon-chimaeric adenovirus serotype 5 vectors circumvent pre-existing anti-vector immunity.” Nature 441.7090 (2006): 239-243.

[0498] Ronzitti, Giuseppe, David-Alexandre Gross, and Federico Mingozzi. “Human immune responses to adeno-associated virus (AAV) vectors.” Frontiers in immunology 11 (2020): 670.

[0499] Ruff, Robert L., and Robert P. Lisak. “Nature and action of antibodies in myasthenia gravis.” Neurologic clinics 36.2 (2018): 275-291.

[0500] Rummler, Silke, et al. “Current techniques for AB0-incompatible living donor liver transplantation.” World journal of transplantation 6.3 (2016): 548.

[0501] Runcie, Karie, et al. “Bi-specific and tri-specific antibodies-the next big thing in solid tumor therapeutics.” Molecular Medicine 24.1 (2018): 50.

[0502] Ryan, Brent J., Ahuva Nissim, and Paul G. Winyard. “Oxidative post-translational modifications and their involvement in the pathogenesis of autoimmune diseases.” Redox biology 2 (2014): 715-724.

[0503] Salganik, Max, Matthew L. Hirsch, and Richard Jude Samulski. “Adeno-associated virus as a mammalian DNA vector.” Mobile DNA III (2015): 827-849.

[0504] Shanmugam, Arulkumaran, et al. “Identification of PSA peptide mimotopes using phage display peptide library.” Peptides 32.6 (2011): 1097-1102.

[0505] Skytthe, Maria K., Jonas Heilskov Graversen, and Søren K. Moestrup. “Targeting of CD163+ Macrophages in Inflammatory and Malignant Diseases.” International Journal of Molecular Sciences 21.15 (2020): 5497.

[0506] Sonntag, F., et al. “The assembly-activating protein promotes capsid assembly of different adeno-associated virus serotypes.” Journal of virology 85.23 (2011): 12686-12697.

[0507] Sørensen, Karen Kristine, et al. “Liver sinusoidal endothelial cells.” Comprehensive Physiology 5.4 (2011): 1751-1774.

[0508] Spiess, Christoph, Qianting Zhai, and Paul J. Carter. “Alternative molecular formats and therapeutic applications for bispecific antibodies.” Molecular immunology 67.2 (2015): 95-106.

[0509] Sunasee, Rajesh, and Ravin Narain. “Covalent and noncovalent bioconjugation strategies.” Chemistry of Bioconjugates: Synthesis, Characterization, and Biomedical Applications (2014): 1-75.

[0510] Taddeo, Adriano, et al. “Selection and depletion of plasma cells based on the specificity of the secreted antibody.” European journal of immunology 45.1 (2015): 317-319.

[0511] Teschner, Sven, et al. “ABO-incompatible kidney transplantation using regenerative selective immunoglobulin adsorption.” Journal of clinical apheresis 27.2 (2012): 51-60.

[0512] Tetala, Kishore KR, et al. “Selective depletion of neuropathy-related antibodies from human serum by monolithic affinity columns containing ganglioside mimics.” Journal of medicinal chemistry 54.10 (2011): 3500-3505.

[0513] Tian, Xingui, et al. “Broadly neutralizing monoclonal antibodies against human adenovirus types 55, 14p, 7, and 11 generated with recombinant type 11 fiber knob.” Emerging microbes & infections 7.1 (2018): 1-12.

[0514] Tseng, Yu-Shan, and Mavis Agbandje-McKenna. “Mapping the AAV capsid host antibody response toward the development of second generation gene delivery vectors.” Frontiers in immunology 5 (2014): 9.

[0515] Varghese, Robin, et al. “Postentry neutralization of adenovirus type 5 by an antihexon antibody.” Journal of virology 78.22 (2004): 12320-12332.

[0516] Verdera, Helena Costa, Klaudia Kuranda, and Federico Mingozzi. “AAV vector immunogenicity in humans: a long journey to successful gene transfer.” Molecular Therapy 28.3 (2020): 723-746.

[0517] Vincent, Angela, et al. “Serological and experimental studies in different forms of myasthenia gravis.” Annals of the New York Academy of Sciences 1413.1 (2018): 143-153.

[0518] Wallukat, Gerd, et al. “Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT 1 receptor.” The Journal of clinical investigation 103.7 (1999): 945-952.

[0519] Wang, Rong, et al. “A Murine Monoclonal Antibody With Potent Neutralization Ability Against Human Adenovirus 7.” Frontiers in cellular and infection microbiology 9 (2019): 417.

[0520] Zhou, Cissy C., et al. “Angiotensin receptor agonistic autoantibodies induce pre-eclampsia in pregnant mice.” Nature medicine 14.8 (2008): 855.

[0521] Zhu, Feng-Cai, et al. “Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial.” The Lancet 395.10240 (2020): 1845-1854.