Fusion proteins for the diagnosis, prophylaxis and treatment of infectious diseases

Abstract

The present invention relates to the use of phosphotidylserine or pathogenic sugar targeted therapeutics for the management and treatment of microbial infections, including Zika, Dengue, West Nile, Ebola, H1N1, enteroviruses, Leishmaniasis, Malaria and Coronaviruses SARS-COV.

Claims

1. A fusion construct comprising an Ig-Fc domain, a peptide, protein or antibody fragment binding to phosphatidylserine, wherein the peptide, protein or antibody fragment binding to phosphatidylserine is selected from TIM-1 and fragments thereof, a peptide or protein binding to and/or recognizing a PAMP expressed by a microbe, wherein the peptide or protein binding to and/or recognizing a PAMP expressed by a microbe is selected from DC-SIGN and fragments thereof, a first chain comprising a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, and a sequence according to SEQ ID No.: 38, and a second chain comprising a sequence according to SEQ ID No.: 3 or SEQ ID No.: 4, and a sequence according to SEQ ID No.: 40.

2. The fusion construct according to claim 1, wherein the Ig-Fc domain is dimeric and comprises heterodimerization mutations involving positions 405 and/or 409 (EU numbering).

3. The fusion construct according to claim 1, wherein said fusion construct is for use in the treatment of an infection.

4. The fusion construct according to claim 3, wherein said infection is an infection caused by a virus, a parasite, a bacteria, a fungi or a protozoan.

5. The fusion construct according to claim 4, wherein said virus is selected among an arborvirus, Zika virus, Dengue virus, West Nile virus, Ebola virus, influenza virus, influenza virus H1N1, Chikungunya virus, enterovirus, Coronavirus SARS-COV-2 and Coronaviruses SARS-COV.

6. The fusion construct according to claim 4, wherein said bacteria is selected among Mycobacterium tuberculosis and Mycobacterium leprae.

7. The fusion construct according to claim 4, wherein said parasite is selected among Leishmaniasis and Malaria.

8. The fusion construct according to claim 1, wherein said fusion construct allows administration through a route selected among subcutaneous administration, intradermal administration, intramuscular administration, oral administration and/or nasal administration.

Description

FIGURES

(1) FIG. 1 shows TIM1 and CTLD constructs with enhanced ADCC, ADCP and CDC.

(2) FIG. 2 shows TIM1 and CTLD constructs with T cell engager activity.

(3) FIG. 3 shows TIM1 and CTLD constructs with furin inhibitor payload.

(4) FIG. 4 shows TIM1 and CTLD constructs with IgM effector function.

(5) All cited references are incorporated by reference.

(6) The accompanying Figures and Examples are provided to explain rather than limit the present invention. It will be clear to the person skilled in the art that aspects, embodiments, claims and any items of the present invention may be combined.

(7) Unless otherwise mentioned, all percentages are in weight/weight. Unless otherwise mentioned, all measurements are conducted under standard conditions (ambient temperature and pressure). Unless otherwise mentioned, test conditions are according to European Pharmacopoeia 8.0.

EXAMPLES

Example 1: Selection of Recombinant Human TIM1 Fragment

(8) Construct V-TIM1-1 was selected as residues 21-125 of the full length TIM-1 sequence (https://www.uniprot.org/uniprot/Q96D42), and V-TIM1-2 was selected as residues 21-127. V-TIM-2 contains an extra two Pro residues at the C-terminal domain boundary.

(9) TABLE-US-00003 TABLE 1 Sequences of Recombinant human TIM1 fragment Predicted  Construct Sequence Mw pl V-TIM1-1 SVKVGGEAGPSVTLPCHYSGAVTSMCWNRGSCSLFTCQNGIV 11.6 8.26 WTNGTHVTYRKDTRYKLLGDLSRRDVSLTIENTAVSDSGVYCC KDa RVEHRGWFNDMKITVSLEIV SEQ. ID No.: 1 V-TIM1-2 SVKVGGEAGPSVTLPCHYSGAVTSMCWNRGSCSLFTCQNGIV 11.8 8.26 WTNGTHVTYRKDTRYKLLGDLSRRDVSLTIENTAVSDSGVYCC KDa RVEHRGWFNDMKITVSLEIVPP SEQ. ID No.: 2

Example 2: Selection of Recombinant Human C-Type Lectin Domain (CTLD) Fragment of DC-SIGN (Cd209)

(10) Construct V-CTLD-1 was selected as residues 250-385 of the full length DC-SIGN sequence (https://www.uniprot.org/uniprot/Q9NNX6), and V-CTLD-2 was selected as residues 254-383. V-CTLD-1 contains 4 internal disulfide bonds, whereas V-CTLD-2 contains 3 internal disulfide bonds.

(11) TABLE-US-00004 TABLE 2 Sequences of Recombinant human CTLD fragment of DC-SIGN Predicted Construct Sequence MW pl V-CTLD-1 ERLCHPCPWEWTFFQGNCYFMSNSQRNWHDSITACKEVGA 15.7 5.12 QLVVIKSAEEQNFLQLQSSRSNRFTWMGLSDLNQEGTWQW KDa VDGSPLLPSFKQYWNRGEPNNVGEEDCAEFSGNGWNDDKC NLAKFWICKKSAASCS SEQ. ID No.: 3 V-CTLD-2 HPCPWEWTFFQGNCYFMSNSQRNWHDSITACKEVGAQLVV 15.0 5.08 IKSAEEQNFLQLQSSRSNRFTWMGLSDLNQEGTWQWVDGS KDa PLLPSFKQYWNRGEPNNVGEEDCAEFSGNGWNDDKCNLAK FWICKKSAAS SEQ. ID No.: 4

Example 3: Design of TIM-1 and CTLD Constructs with IgG3 Effector Functions

(12) Among all human IgG subclasses, IgG3 has the highest effector functions in terms of ADCC, ADCP and CDC (Ref: https://www.frontiersin.org/articles/10.3389/fimmu.2014.00520/full). IgG3 has not typically been used for therapeutics because of the short serum half-life due to proteolytic cleavage of the prolonged hinge region between the CH1 and CH2 domains. To utilize the strong effector functions of the IgG3 subclass, the V-IGG3 construct was designed where the IgG3 hinge (LKTPLGDTTHTPEPKSCDTPPPCPRCPAP) (SEQ ID NO. 6) was replaced with an IgG4 hinge sequence containing an IgG4 hinge S228P mutation to prevent Fab arm exchange (SKYGPPCPPCPAP) (SEQ ID NO. 8) or an IgG1-like hinge (KTGDTTHTCPRCPAP) (SEQ ID NO. 68).

(13) Heterodimeric V-IGG3 constructs were designed based on including K409R (on one half-antibody) and F405L (on second antibody) mutation in the CH3 domains (Reference https://www.nature.com/articles/nprot.2014.169). Each half antibody is first generated as a single homodimer, then mixed together and allowed to recombine as heterodimers under reducing and oxidizing conditions. The resulting sequences are noted as V-IGG3-A and V-IGG3-B and pair together, or V-IGG3-D and V-IGG3-E that pair together. Sequences are found in Table 3, including truncated version that include a (GGGGS)3 linker (SEQ ID NO. 41) to replace the CH1 domains.

(14) TABLE-US-00005 TABLE 3 Modified IgG3 domains Construct Sequence Notes WT hulgG3 ASTKGPSVFPLAPCSRSTSGGTAALGCLVKDYFPEPVTVSW Hinge region underlined as CH1-CH2-CH3 NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYTC SEQ ID No.: 6 NVNHKPSNTKVDKRVELKTPLGDTTHTPEPKSCDTPPPCPR CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE DPEVQFKWYVDGVEVHNAKTKPREEQYNSTFRVVSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKTKGQPREPQVY TLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESSGQPEN NYNTTPPMLDSDGSFFLYSKLTVDKSRWQQGNIFSCSVM HEALHNRFTQKSLSLSPGK SEQ ID No.: 5 V-IGG3 ASTKGPSVFPLAPCSRSTSGGTAALGCLVKDYFPEPVTVSW Hinge region underlined NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYTC (SEQ ID No.: 8) with IgG4 NVNHKPSNTKVDKRVESKYGPPCPPCPAPELLGGPSVFLFP hinge 5228P mutation in PKPKDTLMISRTPEVTCVVVDVSHEDPEVQFKWYVDGVEV bold HNAKTKPREEQYNSTFRVVSVLTVLHQDWLNGKEYKCKVS NKALPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLT CLVKGFYPSDIAVEWESSGQPENNYNTTPPMLDSDGSFFL YSKLTVDKSRWQQGNIFSCSVMHEALHNRFTQKSLSLSPG K SEQ ID No.: 7 V-IGG3-Fc GGGGSGGGGSGGGGSKYGPPCPPCPAPELLGGPSVFLFPP Same as above, but with KPKDTLMISRTPEVTCVVVDVSHEDPEVQFKWYVDGVEV linker and fc only HNAKTKPREEQYNSTFRVVSVLTVLHQDWLNGKEYKCKVS NKALPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLT CLVKGFYPSDIAVEWESSGQPENNYNTTPPMLDSDGSFFL YSKLTVDKSRWQQGNIFSCSVMHEALHNRFTQKSLSLSPG K SEQ ID No.: 9 V-IGG3-A ASTKGPSVFPLAPCSRSTSGGTAALGCLVKDYFPEPVTVSW K409R NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYTC NVNHKPSNTKVDKRVESKYGPPCPPCPAPELLGGPSVFLFP PKPKDTLMISRTPEVTCVVVDVSHEDPEVQFKWYVDGVEV HNAKTKPREEQYNSTFRVVSVLTVLHQDWLNGKEYKCKVS NKALPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLT CLVKGFYPSDIAVEWESSGQPENNYNTTPPMLDSDGSFFL YSRLTVDKSRWQQGNIFSCSVMHEALHNRFTQKSLSLSPG K SEQ ID No.: 10 V-IGG3-A-Fc GGGGSGGGGSGGGGSKYGPPCPPCPAPELLGGPSVFLFPP Same as above, but with KPKDTLMISRTPEVTCVVVDVSHEDPEVQFKWYVDGVEV linker and fc only HNAKTKPREEQYNSTFRVVSVLTVLHQDWLNGKEYKCKVS NKALPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLT CLVKGFYPSDIAVEWESSGQPENNYNTTPPMLDSDGSFFL YSRLTVDKSRWQQGNIFSCSVMHEALHNRFTQKSLSLSPG K SEQ ID No.: 11 V-IGG3-B ASTKGPSVFPLAPCSRSTSGGTAALGCLVKDYFPEPVTVSW F405L NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYTC NVNHKPSNTKVDKRVESKYGPPCPPCPAPELLGGPSVFLFP PKPKDTLMISRTPEVTCVVVDVSHEDPEVQFKWYVDGVEV HNAKTKPREEQYNSTFRVVSVLTVLHQDWLNGKEYKCKVS NKALPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLT CLVKGFYPSDIAVEWESSGQPENNYNTTPPMLDSDGSFLL YSKLTVDKSRWQQGNIFSCSVMHEALHNRFTQKSLSLSPG K SEQ ID No.: 12 V-IGG3-B-Fc GGGGSGGGGSGGGGSKYGPPCPPCPAPELLGGPSVFLFPP Same as above, but with KPKDTLMISRTPEVTCVVVDVSHEDPEVQFKWYVDGVEV linker and fc only HNAKTKPREEQYNSTFRVVSVLTVLHQDWLNGKEYKCKVS NKALPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLT CLVKGFYPSDIAVEWESSGQPENNYNTTPPMLDSDGSFLL YSKLTVDKSRWQQGNIFSCSVMHEALHNRFTQKSLSLSPG K SEQ ID No.: 13 V-IGG3-C ASTKGPSVFPLAPCSRSTSGGTAALGCLVKDYFPEPVTVSW Utilizes an IgG1-like hinge NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYTC NVNHKPSNTKVDKRVELKTGDTTHTCPRCPAPELLGGPSV FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFKWYVD GVEVHNAKTKPREEQYNSTFRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKTKGQPREPQVYTLPPSREEMTKN QVSLTCLVKGFYPSDIAVEWESSGQPENNYNTTPPMLDSD GSFFLYSKLTVDKSRWQQGNIFSCSVMHEALHNRFTQKSL SLSPGK SEQ ID No.: 42 V-IGG3-C-Fc GGGGSGGGGSGGGGSKTGDTTHTCPRCPAPELLGGPSVF Same as above, but with LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFKWYVDG linker and fc only VEVHNAKTKPREEQYNSTFRVVSVLTVLHQDWLNGKEYKC KVSNKALPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESSGQPENNYNTTPPMLDSDG SFFLYSKLTVDKSRWQQGNIFSCSVMHEALHNRFTQKSLSL SPGK SEQ ID No.: 43 V-IGG3-D ASTKGPSVFPLAPCSRSTSGGTAALGCLVKDYFPEPVTVSW K409R NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYTC NVNHKPSNTKVDKRVELKTGDTTHTCPRCPAPELLGGPSV FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFKWYVD GVEVHNAKTKPREEQYNSTFRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKTKGQPREPQVYTLPPSREEMTKN QVSLTCLVKGFYPSDIAVEWESSGQPENNYNTTPPMLDSD GSFFLYSRLTVDKSRWQQGNIFSCSVMHEALHNRFTQKSL SLSPGK SEQ ID No.: 44 V-IGG3-D-Fc GGGGSGGGGSGGGGSKTGDTTHTCPRCPAPELLGGPSVF Same as above, but with LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFKWYVDG linker and fc only VEVHNAKTKPREEQYNSTFRVVSVLTVLHQDWLNGKEYKC KVSNKALPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESSGQPENNYNTTPPMLDSDG SFFLYSRLTVDKSRWQQGNIFSCSVMHEALHNRFTQKSLSL SPGK SEQ ID No.: 45 V-IGG3-E ASTKGPSVFPLAPCSRSTSGGTAALGCLVKDYFPEPVTVSW F405L NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYTC NVNHKPSNTKVDKRVELKTGDTTHTCPRCPAPELLGGPSV FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFKWYVD GVEVHNAKTKPREEQYNSTFRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKTKGQPREPQVYTLPPSREEMTKN QVSLTCLVKGFYPSDIAVEWESSGQPENNYNTTPPMLDSD GSFLLYSKLTVDKSRWQQGNIFSCSVMHEALHNRFTQKSL SLSPGK SEQ ID No.: 46 V-IGG3-E-Fc GGGGSGGGGSGGGGSKTGDTTHTCPRCPAPELLGGPSVF Same as above, but with LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFKWYVDG linker and fc only VEVHNAKTKPREEQYNSTFRVVSVLTVLHQDWLNGKEYKC KVSNKALPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESSGQPENNYNTTPPMLDSDG SFLLYSKLTVDKSRWQQGNIFSCSVMHEALHNRFTQKSLSL SPGK SEQ ID No.: 47

(15) TIM1 and CTLD fusion proteins were designed with the modified IgG3-Fc domains and are depicted in FIG. 1 and Table 4.

(16) TABLE-US-00006 TABLE 4 Sequences of TIM-1 and CTLD constructs with  enhanced ADCC, ADCP and CDC Con- struct Chain 1 Chain 2 VIT-300 (V-TIM1-1/V-TIM1-2)- Same as Chain 1 V-IGG3-Fc/V-IGG3-C-Fc VIT-301 (V-CTLD-1/V-CTLD-2)- Same as Chain 1 V-IGG3-Fc/V-IGG3-C-Fc VIT-302 (V-TIM1-1/V-TIM1-2)- (V-CTLD-1/V-CTLD-2)- V-IGG3-A-Fc/V-IGG3-D-Fc V-IGG3-B-Fc/V-IGG3- E-Fc

Example 4. Design of TIM-1 and CTLD Constructs with T Cell Engaging Activity

(17) Additional constructs were designed to engage T cell effector functions by fusing the TIM-1 and CTLD with a single anti-CD3 scFv. The designs are shown in FIG. 2 and Table 5.

(18) Table 5. Sequences of TIM-1 and CTLD Constructs with T Cell Engager Activity

(19) TABLE-US-00007 Construct Chain 1 Chain 2 VIT-303 (V-TIM1-1/V-TIM1-2)- (V-TIM1-1/V-TIM1-2)- (V-IGG4-A-Fc/V-IGG2- (V-IGG4-B-Fc/V-IGG2- A-Fc/V-IGG2-D-Fc) B-Fc/V-IGG2-E-Fc)- GGGGSGGGGSGGGGS  (SEQ ID No.: 41)- (anti-CD3 scFv) VIT-304 (V-CTLD-1/V-CTLD-2)- (V-CTLD-1/V-CTLD-2)- (V-IGG4-A-Fc/V-IGG2- (V-IGG4-B-Fc/V-IGG2- A-Fc/V-IGG2-D-Fc) B-Fc/V-IGG2-E-Fc)- GGGGSGGGGSGGGGS  (SEQ ID No.: 41)- (anti-CD3 scFv) VIT-305 (V-TIM1-1/V-TIM1-2)- (V-CTLD-1/V-CTLD-2)- (V-IGG4-A-Fc/V-IGG2- (V-IGG4-B-Fc/V-IGG2- A-Fc/V-IGG2-D-Fc) B-Fc/V-IGG2-E-Fc)- GGGGSGGGGSGGGGS  (SEQ ID No.: 41)- (anti-CD3 scFv) VIT-306 (V-TIM1-1/V-TIM1-2)- (V-CTLD-1/V-CTLD-2)- (V-IGG4-B-Fc/V-IGG2- GGGGSGGGGSGGGGS  B-Fc/V-IGG2-E-Fc)- (SEQ ID No.: 41)- GGGGSGGGGSGGGGS  (V-IGG4-A-Fc/V-IGG2- (SEQ ID No.: 41)- A-Fc/V-IGG2-D-Fc) (anti-CD3 scFv)

(20) Anti-CD3 scFv Sequences are Described Below

(21) TABLE-US-00008 Construct Sequence VCD3- QVQLVQSGGGVVQPGRSLRLSCAASGYTFTRYTMHWVRQAPGKGLEWVGYINPSRGYTNYNDSV H1L1 KGRFTISTDKSKNTAYLQMNSLRAEDTAVYYCARYYDDHYSLDYWGQGTTVTVSSGGGGSGGGGS GGGGSGGGGSGGGGSGGGGS DIQMTQSPSSLSASVGDRVTITCQASSSVSYMNWYQQKPGKAPKRWIYDTSKLASGVPSRFSGSGS GTDYTFTISSLQPEDIATYYCQQWSSNPFTFGQGTKLEIK(SEQ ID NO: 18) VCD3- QVQLVQSGGGVVQPGRSLRLSCAASGYTFTRYTMHWVRQAPGKCLEWVGYINPSRGYTNYNDSV H1L1-DS KGRFTISTDKSKNTAYLQMNSLRAEDTAVYYCARYYDDHYSLDYWGQGTTVTVSSGGGGSGGGGS GGGGSGGGGSGGGGSGGGGS DIQMTQSPSSLSASVGDRVTITCQASSSVSYMNWYQQKPGKAPKRWIYDTSKLASGVPSRFSGSGS GTDYTFTISSLQPEDIATYYCQQWSSNPFTFGCGTKLEIK(SEQ ID NO: 19) VCD3- QVQLVQSGGGVVQPGRSLRLSCAASGYTFTRYTMHWVRQAPGKGLEWVGYINPSRGYTNYNDSV H1L2 KGRFTISTDKSKNTAYLQMNSLRAEDTAVYYCARYYDDHYSLDYWGQGTTVTVSSGGGGSGGGGS GGGGSGGGGSGGGGSGGGGS EIVLTQSPATLSLSPGERATLSCRASSSVSYMNWYQQKPGQAPRRLIYDTSKRATGIPARFSGSGSGT DYTLTISSLEPEDAAVYYCQQWSSNPFTFGQGTKLEIK(SEQ ID NO: 20) VCD3- QVQLVQSGGGVVQPGRSLRLSCAASGYTFTRYTMHWVRQAPGKCLEWVGYINPSRGYTNYNDSV H1L2-DS KGRFTISTDKSKNTAYLQMNSLRAEDTAVYYCARYYDDHYSLDYWGQGTTVTVSSGGGGSGGGGS GGGGSGGGGSGGGGSGGGGS EIVLTQSPATLSLSPGERATLSCRASSSVSYMNWYQQKPGQAPRRLIYDTSKRATGIPARFSGSGSGT DYTLTISSLEPEDAAVYYCQQWSSNPFTFGCGTKLEIK(SEQ ID NO: 21) VCD3- QVQLVQSGGGVVQPGRSLRLSCAASGYTFTRYTMHWVRQAPGKGLEWVGYINPSRGYTNYNDSV H1L3 KGRFTISTDKSKNTAYLQMNSLRAEDTAVYYCARYYDDHYSLDYWGQGTTVTVSSGGGGSGGGGS GGGGSGGGGSGGGGSGGGGS EIQLTQSPATLSLSPGERATLSCRASSSVSYMNWYQQKPGQAPRRWIYDTSKLATGIPARFSGSGSGT DYTLTISSLEPEDAAVYYCQQWSSNPFTFGQGTKLEIK(SEQ ID NO: 22) VCD3- QVQLVQSGGGVVQPGRSLRLSCAASGYTFTRYTMHWVRQAPGKCLEWVGYINPSRGYTNYNDSV H1L3-DS KGRFTISTDKSKNTAYLQMNSLRAEDTAVYYCARYYDDHYSLDYWGQGTTVTVSSGGGGSGGGGS GGGGSGGGGSGGGGSGGGGS EIQLTQSPATLSLSPGERATLSCRASSSVSYMNWYQQKPGQAPRRWIYDTSKLATGIPARFSGSGSGT DYTLTISSLEPEDAAVYYCQQWSSNPFTFGCGTKLEIK(SEQ ID NO: 23) VCD3- QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYTMHWVRQAPGQGLEWMGYINPSRGYTNYNQKF H2L1 QGRVTMTTDKSTSTAYMELSSLRSEDTAVYYCARYYDDHYSLDYWGQGTTVTVSSGGGGSGGGGS GGGGSGGGGSGGGGSGGGGS DIQMTQSPSSLSASVGDRVTITCQASSSVSYMNWYQQKPGKAPKRWIYDTSKLASGVPSRFSGSGS GTDYTFTISSLQPEDIATYYCQQWSSNPFTFGQGTKLEIK(SEQ ID NO: 24) VCD3- QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYTMHWVRQAPGQCLEWMGYINPSRGYTNYNQKF H2L1-DS QGRVTMTTDKSTSTAYMELSSLRSEDTAVYYCARYYDDHYSLDYWGQGTTVTVSSGGGGSGGGGS GGGGSGGGGSGGGGSGGGGS DIQMTQSPSSLSASVGDRVTITCQASSSVSYMNWYQQKPGKAPKRWIYDTSKLASGVPSRFSGSGS GTDYTFTISSLQPEDIATYYCQQWSSNPFTFGCGTKLEIK(SEQ ID NO: 25) VCD3- QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYTMHWVRQAPGQGLEWMGYINPSRGYTNYNQKF H2L2 QGRVTMTTDKSTSTAYMELSSLRSEDTAVYYCARYYDDHYSLDYWGQGTTVTVSSGGGGSGGGGS GGGGSGGGGSGGGGSGGGGS EIVLTQSPATLSLSPGERATLSCRASSSVSYMNWYQQKPGQAPRRLIYDTSKRATGIPARFSGSGSGT DYTLTISSLEPEDAAVYYCQQWSSNPFTFGQGTKLEIK(SEQ ID NO: 26) VCD3- QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYTMHWVRQAPGQCLEWMGYINPSRGYTNYNQKF H2L2-DS QGRVTMTTDKSTSTAYMELSSLRSEDTAVYYCARYYDDHYSLDYWGQGTTVTVSSGGGGSGGGGS GGGGSGGGGSGGGGSGGGGS EIVLTQSPATLSLSPGERATLSCRASSSVSYMNWYQQKPGQAPRRLIYDTSKRATGIPARFSGSGSGT DYTLTISSLEPEDAAVYYCQQWSSNPFTFGCGTKLEIK(SEQ ID NO: 27) VCD3- QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYTMHWVRQAPGQGLEWMGYINPSRGYTNYNQKF H2L3 QGRVTMTTDKSTSTAYMELSSLRSEDTAVYYCARYYDDHYSLDYWGQGTTVTVSSGGGGSGGGGS GGGGSGGGGSGGGGSGGGGS EIQLTQSPATLSLSPGERATLSCRASSSVSYMNWYQQKPGQAPRRWIYDTSKLATGIPARFSGSGSGT DYTLTISSLEPEDAAVYYCQQWSSNPFTFGQGTKLEIK(SEQ ID NO: 28) VCD3- QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYTMHWVRQAPGQCLEWMGYINPSRGYTNYNQKF H2L3-DS QGRVTMTTDKSTSTAYMELSSLRSEDTAVYYCARYYDDHYSLDYWGQGTTVTVSSGGGGSGGGGS GGGGSGGGGSGGGGSGGGGS EIQLTQSPATLSLSPGERATLSCRASSSVSYMNWYQQKPGQAPRRWIYDTSKLATGIPARFSGSGSGT DYTLTISSLEPEDAAVYYCQQWSSNPFTFGCGTKLEIK(SEQ ID NO: 29) VCD3- QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYTMHWVRQSPGQGLEWMGYINPSRGYTNYNQKF H3L1 QGRVTMTTDKSTSTAYMELSSLRSEDTAVYYCARYYDDHYSLDYWGQGTTVTVSSGGGGSGGGGS GGGGSGGGGSGGGGSGGGGS DIQMTQSPSSLSASVGDRVTITCQASSSVSYMNWYQQKPGKAPKRWIYDTSKLASGVPSRFSGSGS GTDYTFTISSLQPEDIATYYCQQWSSNPFTFGQGTKLEIK(SEQ ID NO: 30) VCD3- QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYTMHWVRQSPGQCLEWMGYINPSRGYTNYNQKF H3L1-DS QGRVTMTTDKSTSTAYMELSSLRSEDTAVYYCARYYDDHYSLDYWGQGTTVTVSSGGGGSGGGGS GGGGSGGGGSGGGGSGGGGS DIQMTQSPSSLSASVGDRVTITCQASSSVSYMNWYQQKPGKAPKRWIYDTSKLASGVPSRFSGSGS GTDYTFTISSLQPEDIATYYCQQWSSNPFTFGCGTKLEIK(SEQ ID NO: 31) VCD3- QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYTMHWVRQSPGQGLEWMGYINPSRGYTNYNQKF H3L2 QGRVTMTTDKSTSTAYMELSSLRSEDTAVYYCARYYDDHYSLDYWGQGTTVTVSSGGGGSGGGGS GGGGSGGGGSGGGGSGGGGS EIVLTQSPATLSLSPGERATLSCRASSSVSYMNWYQQKPGQAPRRLIYDTSKRATGIPARFSGSGSGT DYTLTISSLEPEDAAVYYCQQWSSNPFTFGQGTKLEIK(SEQ ID NO: 32) VCD3- QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYTMHWVRQSPGQCLEWMGYINPSRGYTNYNQKF H3L2-DS QGRVTMTTDKSTSTAYMELSSLRSEDTAVYYCARYYDDHYSLDYWGQGTTVTVSSGGGGSGGGGS GGGGSGGGGSGGGGSGGGGS EIVLTQSPATLSLSPGERATLSCRASSSVSYMNWYQQKPGQAPRRLIYDTSKRATGIPARFSGSGSGT DYTLTISSLEPEDAAVYYCQQWSSNPFTFGCGTKLEIK(SEQ ID NO: 33) VCD3- QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYTMHWVRQSPGQGLEWMGYINPSRGYTNYNQKF H3L3 QGRVTMTTDKSTSTAYMELSSLRSEDTAVYYCARYYDDHYSLDYWGQGTTVTVSSGGGGSGGGGS GGGGSGGGGSGGGGSGGGGS EIQLTQSPATLSLSPGERATLSCRASSSVSYMNWYQQKPGQAPRRWIYDTSKLATGIPARFSGSGSGT DYTLTISSLEPEDAAVYYCQQWSSNPFTFGQGTKLEIK(SEQ ID NO: 34) VCD3- QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYTMHWVRQSPGQCLEWMGYINPSRGYTNYNQKF H3L3-DS QGRVTMTTDKSTSTAYMELSSLRSEDTAVYYCARYYDDHYSLDYWGQGTTVTVSSGGGGSGGGGS GGGGSGGGGSGGGGSGGGGS EIQLTQSPATLSLSPGERATLSCRASSSVSYMNWYQQKPGQAPRRWIYDTSKLATGIPARFSGSGSGT DYTLTISSLEPEDAAVYYCQQWSSNPFTFGCGTKLEIK(SEQ ID NO: 35)

Example 5. Design of TIM-1 and CTLD Constructs with Furin Inhibitor Payload Delivery

(22) Site specific addition of drug payloads to the antibody Fc region was devised by analysis of the co-crystal structure of a human IgG1 Fc with the 3-helix bundle of bacterial protein A (PDB structure 5U4Y https://www.rcsb.org/sequence/5U4Y). Computational modelling revealed that A339C would have a stabilizing effect to the structure and S337C or K340C would have a neutral effect to the stability of the Fc domain. A339C was chosen as the site for site specific conjugation.

(23) TABLE-US-00009 TABLE 5 IgG4 sequences with engineered free cys for site  specific payload conjugation Construct Sequence Notes V-IGG4-ADC-A ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPE S228P PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVV FALA (F234A, L235A) TVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYG K322A PPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTP Naturally contains EVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKT F405 and R409 KPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCA A339C VSNKGLPSSIEKTISKCKGQPREPQVYTLPPSQEE MTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNV FSCSVMHEALHNHYTQKSLSLSLGK SEQ ID No.: 37 V-IGG4-ADC-A-Fc GGGGSGGGGSGGGGSKYGPPCPPCPAPEAAGG Same as above, but PSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDP with linker and fc  EVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV only SVLTVLHQDWLNGKEYKCAVSNKGLPSSIEKTISK CKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYSRLTVDKSRWQEGNVFSCSVMHEALHNHYT QKSLSLSLGK SEQ ID No.: 38 V-IGG4-ADC-B ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPE S228P PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVV FALA (F234A, L235A) TVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYG K322A PPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTP F405L, R409K EVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKT A339C KPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCA VSNKGLPSSIEKTISKCKGQPREPQVYTLPPSQEE MTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFLLYSKLTVDKSRWQEGNVF SCSVMHEALHNHYTQKSLSLSLGK SEQ ID No.: 39 V-IGG4-ADC-B-Fc GGGGSGGGGSGGGGSKYGPPCPPCPAPEAAGG Same as above, but PSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDP with linker and fc  EVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV only SVLTVLHQDWLNGKEYKCAVSNKGLPSSIEKTISK CKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFL LYSKLTVDKSRWQEGNVFSCSVMHEALHNHYT QKSLSLSLGK SEQ ID No.: 40

(24) TIM1 and CTLD fusion proteins with Fc domain with payload conjugation sites were designed and are shown in FIG. 3 and Table 6.

(25) TABLE-US-00010 TABLE 6 Sequences of TIM1 and CTLD therapeutic proteins  with free cys for payload conjugation Construct Chain 1 Chain 2 VIT-307 (V-TIM1-1/V-TIM1-2)- Same as Chain 1 V-IGG4-ADC-A-Fc VIT-308 (V-CTLD-1/V-CTLD-2)- Same as Chain 1 V-IGG4-ADC-A-Fc VIT-309 (V-TIM1-1/V-TIM1-2)- (V-CTLD-1/V-CTLD-2)- V-IGG4-ADC-A-Fc V-IGG4-ADC-B-Fc

Example 6. Furin Linkers

(26) Decanoyl-Arg-Val-Lys-Arg-chloromethylketone (dec-RVKR-cmk) (SEQ ID NO. 81) or hexa-D-arginine (D6R) were linked to TIM-1 and CTLD constructs using cleavable linkers such as acid sensitive N-acyl-hydrazone or enzyme sensitive malemeide-conjugated dipeptides, valine-alanine, valine-citrulline, or phenylalanine-Lysine.

(27) Acid sensitive linkers are cleaved in the lysosome acidic environment after internalization of the construct. This strategy has been used in two approved ADCs, Gemtuzumab ozogamicin and Inotuzumab ozogamicin. Lysosomal protease sensitive dipeptides release the drug after cleavage by proteases such as cathepsin B-lysosomal protease. This type of linker chemistry has been used for FDA approved Brentuximab vedotin.

(28) Linkage to the polypeptide of antibodies is done through the nucleophilic groups of lysine or cysteine by random conjugation, generating a heterogeneous mixture of conjugates, or by site-directed conjugation to engineered cysteines, reducing the heterogeneity of the product to an antibody-drug ratio (ADR) of 1 or 2.

(29) The nucleophilic reactivity of the thiol functionality of a Cys residue to a maleimide group is about 1000 times higher compared to any other amino acid functionality in a protein, such as amino group of lysine residues or the N-terminal amino group. Thiol specific functionality in maleimide reagents may react with amine groups, but higher pH (>9.0) and longer reaction times are required (Garman, 1997, Non-Radioactive Labelling: A Practical Approach, Academic Press, London).

(30) The first FDA approved site-directed ADC through engineered cysteines was vadastuximab talirine (Seattle Genetics).

(31) TABLE-US-00011 TABLE 7 Linker Chemistry Residue Spacer 1 Linker Spacer 2 Drug Cysteine, Maleimidocaproyl VC, VA, PL para-amino hexa-D- engineered (mc), benzyloxycarbonyl arginine, Cysteine maleimidomethyl (PABC) dec-RVKR- cyclohexane-1- cmk carboxylate (comprising SEQ. ID NO. 81) Lysine NA N-acyl- NA hexa-D- hydrozone, N- arginine, succinimidyl-4- dec-RVKR- (2-pyridyldithio) cmk Butanoate- (comprising disulfide (SPDB- SEQ. ID NO. disulfide), 81) maleimidomethyl cyclohexane-1- carboxylate, sulfo-SPDB

(32) Spacer 1: The purpose of the mc spacer is to provide enough room so that the vc group can be recognized by cathepsin B, which cleaves the citrulline-PABC amide bond.

(33) Spacer 2: Self-immolative spacer

Example 7. Fusion Proteins with IgM Constant Regions

(34) IgM molecules have robust Fc effector functions, particularly with CDC. IgM molecules naturally homodimerize and then covalently associate into pentamers or hexamers. IgM do not contain hinge regions like IgG molecules and instead contain an extra CH domain (CH1-CH2-CH3-CH4). The homodimeric heavy chains come together at the CH2 and CH4 domains. Based on visual analyses of the crystal structure of the murine IgM CH2 domain (pdb 4JVU), the crystal structure of the murine IgM CH4 domain (pdb 4JVW), and a sequence alignment of the human IgM CH2 and CH4 sequences with the homologous mouse sequences, mutations were designed to induce IgM heavy chain heterodimerization by inducing charge differences at the homodimerization interfaces.

(35) Sequence of human IgM constant region, numbered residues 1-453 by uniprot (www_uniprot.org/uniprot/P01871):

(36) TABLE-US-00012 SEQ ID No.: 64 GSASAPTLFPLVSCENSPSDTSSVAVGCLAQDFLPDSITFSWKYKNNSD ISSTRGFPSVLRGGKYAATSQVLLPSKDVMQGTDEHVVCKVQHPNGNKE KNVPLPVIAELPPKVSVFVPPRDGFFGNPRKSKLICQATGFSPRQIQVS WLREGKQVGSGVTTDQVQAEAKESGPTTYKVTSTLTIKESDWLGQSMFT CRVDHRGLTFQQNASSMCVPDQDTAIRVFAIPPSFASIFLTKSTKLTCL VTDLTTYDSVTISWTRQNGEAVKTHTNISESHPNATFSAVGEASICEDD WNSGERFTCTVTHTDLPSPLKQTISRPKGVALHRPDVYLLPPAREQLNL RESATITCLVTGFSPADVFVQWMQRGQPLSPEKYVTSAPMPEPQAPGRY FAHSILTVSEEEWNTGETYTCVVAHEALPNRVTERTVDKSTGKPTLYNV SLVMSDTAGTCY 

(37) Sequence of IgM CH2-CH3-CH4 which can used for fusing to antibody fragments (Fab, scFv, VHH, etc) or targeting proteins (TIM-1, CTLD/DC-SIGN) for adding IgM effector functions (residues 105-453):

(38) V-IGM

(39) TABLE-US-00013 SEQ. ID No.: 65  VIAELPPKVSVFVPPRDGFFGNPRKSKLICQATGFSPRQIQVSWLREGK QVGSGVTTDQVQAEAKESGPTTYKVTSTLTIKESDWLGQSMFTCRVDHR GLTFQQNASSMCVPDQDTAIRVFAIPPSFASIFLTKSTKLTCLVTDLTT YDSVTISWTRQNGEAVKTHTNISESHPNATFSAVGEASICEDDWNSGER FTCTVTHTDLPSPLKQTISRPKGVALHRPDVYLLPPAREQLNLRESATI TCLVTGFSPADVFVQWMQRGQPLSPEKYVTSAPMPEPQAPGRYFAHSIL TVSEEEWNTGETYTCVVAHEALPNRVTERTVDKSTGKPTLYNVSLVMSD  TAGTCY

(40) Based on the structural analysis, the underlined residues K131 and Q135 were found to be in close proximity in the CH2:CH2 interface, and residues T354 and E385 were found to be in close proximity in the CH4:CH4 interface. The following mutations were made to alter the charge pattern in V-IGM-A and V-IGM-B to induce heterodimer formation of A:B and repel the formations of A:A or B:B.

(41) TABLE-US-00014 TABLE 8 IgM constant region mutations to induce heavy chain heterodimer formation Wildtype residue Position in V-IGM V-IGM-A V-IGM-B 131 K K/R/H D/E 135 Q K/R/H D/E 354 T D/E K/R/H 385 E D/E K/R/H

(42) TIM1 and CTLD fusion proteins with IgM effector functions were designed and shown in Table 9.

(43) TABLE-US-00015 TABLE 9 Sequences of TIM1 and CTLD therapeutic proteins  with IgM effector functions Construct Chain 1 Chain 2 VIT-310 (V-TIM1-1/V-TIM1-2)- Same as Chain 1 GGGGSGGGGSGGGGS  (SEQ ID No.: 41)- V-IGM VIT-311 (V-CTLD-1/V-CTLD-2)- Same as Chain 1 GGGGSGGGGSGGGGS  (SEQ ID No.: 41)- V-IGM VIT-312 (V-TIM1-1/V-TIM1-2)- (V-CTLD-1/V-CTLD-2)- GGGGSGGGGSGGGGS  GGGGSGGGGSGGGGS  (SEQ ID No.: 41)- (SEQ ID No.: 41)- V-IGM-A V-IGM-B

(44) The invention is further described by the following items: 1. A fusion construct comprising an Ig-Fc domain or other protein scaffold, such as albumin or an antibody fragment binding to albumin, and a. a peptide, protein or antibody fragment binding to phosphatidylserine and/or b. a peptide or protein binding to and/or recognizing a PAMP expressed by a microbe. 2. A fusion construct, preferably according to any of the preceding items comprising an IgG-Fc domain or other protein scaffold and a. a recombinant human TIM1 fragment and/or b. a recombinant human CD209 fragment. 3. A fusion construct, preferably according to any of the preceding items comprising an IgG-Fc domain or other protein scaffold and a. a recombinant human TIM1 fragment and/or b. a recombinant human CD209 fragment and wherein said fusion construct provides enhanced ADCC, ADCP and/or CDC. 4. A fusion construct, preferably according to any of the preceding items comprising an IgG-Fc domain or other protein scaffold and a. a recombinant human TIM1 fragment and/or b. a recombinant human CD209 fragment  and wherein said fusion construct additionally comprises the CDR regions according to SEQ ID No.: 54-59. 5. A fusion construct, preferably according to any of the preceding items comprising an IgG-Fc domain or other protein scaffold and a. a recombinant human TIM1 fragment and/or b. a recombinant human CD209 fragment  and wherein said fusion construct further comprises a Furin inhibitor. 6. The fusion construct according to any of the preceding items, wherein said peptide, protein or antibody fragment is capable of binding to and/or stimulating an immune cell. 7. The fusion construct according to any of the preceding items, wherein said TIM1 fragment has a sequence length selected from the group consisting of 40-200 amino acid residues, 50-180 amino acid residues, 60-160 amino acid residues, 70-140 amino acid residues, 80-130 amino acid residues, 90-120 amino acid residues, 100-120 amino acid residues and 100-110 amino acid residues. 8. The fusion construct according to any of the preceding items, wherein said CD209 fragment has a sequence length selected from the group consisting of 40-200 amino acid residues, 40-190 amino acid residues, 50-180 amino acid residues, 60-170 amino acid residues, 70-160 amino acid residues, 80-150 amino acid residues, 90-150 amino acid residues, 100-150 amino acid residues, 110-150 amino acid residues, 120-150 amino acid residues and 130-140 amino acid residues. 9. The fusion construct according to any of the preceding items, wherein said TIM1 and/or CD209 fragment has a sequence homology of at least 70%, alternatively 75%, alternatively 80%, alternatively 85%, alternatively 90%, alternatively 95% to wildtype TIM1 or CD209. 10. The fusion construct according to any of the preceding items, wherein said TIM1 and/or CD209 fragment has intact TIM1 and/or CD209 function. 11. The fusion construct according to any of the preceding items, wherein said IgG-Fc domain is an IgG3-Fc domain. 12. The fusion construct according to any of the preceding items, comprising additionally at least one of the following: a) An IgG3, wherein the hinge sequence has been replaced, preferably with an IgG4 or IgG1 hinge sequence; b) CDR regions according to SEQ ID No.: 54-59; and/or c) A furin inhibitor. 13. The fusion construct according to any of the preceding items, wherein said fusion construct comprises a sequence according to SEQ ID No.: 1 and/or SEQ ID No.: 2. 14. The fusion construct according to any of the preceding items, wherein said fusion construct comprises a sequence according to SEQ ID No.: 3 and/or SEQ ID No.: 4. 15. The fusion construct according to any of the preceding items, wherein said fusion construct comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7 or preferably at least 8 disulfide bonds. 16. The fusion construct according to any of the preceding items, wherein said fusion construct is capable of binding to a target, and wherein said target is a mannan, a high-mannose containing structure, a fucan, a phospholipid phosphatidylserine and/or CD3. 17. The fusion construct according to any of the preceding items, wherein said fusion construct comprises: a. A first chain comprising i. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2 and ii. a sequence according to SEQ ID No.: 9 or a sequence according to SEQ ID No.: 43, and b. A second chain comprising iii. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, and iv. a sequence according to SEQ ID No.: 9 or a sequence according to SEQ ID No.: 43. 18. The fusion construct according to any of the preceding items, wherein said fusion construct comprises: a. A first chain comprising i. a sequence according to SEQ ID No.: 3 or SEQ ID No.: 4, and ii. a sequence according to SEQ ID No.: 9 or a sequence according to SEQ ID No.: 43, and b. A second chain comprising iii. a sequence according to SEQ ID SEQ ID No.: 3 or SEQ ID No.: 4, and iv. a sequence according to SEQ ID No.: 9 or a sequence according to SEQ ID No.: 43. 19. The fusion construct according to any of the preceding items, wherein said fusion construct comprises: a. A first chain comprising i. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, and ii. a sequence according to SEQ ID No.: 11 or a sequence according to SEQ ID No.: 45, and b. A second chain comprising iii. a sequence according to SEQ ID No.: 3 or SEQ ID No.: 4, and iv. a sequence according to SEQ ID No.: 13 or a sequence according to SEQ ID No.: 47. 20. The fusion construct according to any of the preceding items, wherein said fusion construct comprises: a. A first chain comprising i. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, and ii. a sequence according to SEQ ID No.: 14 or 15, or SEQ ID No.: 66, and b. A second chain comprising iii. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, and iv. a sequence according to SEQ ID No.: 16 or 17, or SEQ ID No.: 67 and v. a linker sequence, preferably according to SEQ ID No.: 41, and vi. a sequence according to any of the sequences selected among SEQ ID No.: 18-35. 21. The fusion construct according to any of the preceding items, wherein said fusion construct comprises: a. A first chain comprising i. a sequence according to SEQ ID No.: 3 or SEQ ID No.: 4, and ii. a sequence according to SEQ ID No.: 14 or 15, or SEQ ID No.: 66, and b. A second chain comprising iii. a sequence according to SEQ ID No.: 3 and/or SEQ ID No.: 4, and iv. a sequence according to SEQ ID No.: 16 or 17, or SEQ ID No.: 67 and v. a linker sequence preferably according to SEQ ID No.: 41, and vi. a sequence according to any of the sequences selected among SEQ ID No.: 18-35. 22. The fusion construct according to any of the preceding items, wherein said fusion construct comprises: a. A first chain comprising i. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, and ii. a sequence according to SEQ ID No.: 14 or 15, or SEQ ID No.: 66, and b. A second chain comprising iii. a sequence according to SEQ ID No.: 3 or SEQ ID No.: 4, and iv. a sequence according to SEQ ID No.: 16 or 17, or SEQ ID No.: 67, and v. a linker sequence preferably according to SEQ ID No.: 41, and vi. a sequence according to any of the sequences selected among SEQ ID No.: 18-35. 23. The fusion construct according to any of the preceding items, wherein said fusion construct comprises a. A first chain comprising i. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, and ii. a sequence according to SEQ ID No.: 16 or 17, or SEQ ID No.: 67, and iii. a linker sequence preferably according to SEQ ID No.: 41, and iv. a sequence according to any of the sequences selected among SEQ ID No.: 18-35, and b. A second chain comprising v. a sequence according to SEQ ID No.: 3 or SEQ ID No.: 4, vi. a linker sequence preferably according to SEQ ID No.: 41, and vii. a sequence according SEQ ID No.: 14 or 15, or SEQ ID No.: 66. 24. The fusion construct according to any of the preceding items, wherein said fusion construct comprises a linker. 25. The fusion construct according to any of the preceding items, wherein said linker is selected among a (GGGGS)3 linker (SEQ ID NO. 41), a (GGGGS)4 linker (SEQ ID NO. 70), a (GGGGS)5 linker (SEQ ID NO. 71) and a (GGGGS)6 linker (SEQ ID NO. 72). 26. The fusion construct according to any of the preceding items, wherein said fusion construct comprises at least one free cysteine residue, at least two free cysteine residues, at least three free cysteine residues, at least four free cysteine residues, at least five free cysteine residues or preferably at least six free cysteine residues. 27. The fusion construct according to any of the preceding items, wherein said free cysteine allows interaction with a drug and/or a payload. 28. The fusion construct according to any of the preceding items, wherein said payload is a furin inhibitor. 29. The fusion construct according to any of the preceding items, wherein said fusion construct comprises a A339C mutation, a S337C mutation and/or a K340C mutation. 30. The fusion construct according to any of the preceding items, wherein said fusion construct comprises a sequence selected among any of the sequences SEQ ID No.: 36, 37, SEQ ID No.: 38, 39, 40, 42, 44 or 46. 31. The fusion construct according to any of the preceding items, wherein said fusion construct is an IgG1, IgG2, IgG3 or an IgG4. 32. The fusion construct according to any of the preceding items, wherein said fusion construct is an IgG, IgM, IgA, IgD or an IgE. 33. The fusion construct according to any of the preceding items, wherein said fusion construct comprises a null fc. 34. The fusion construct according to any of the preceding items, wherein said null fc comprises an Ala substitution at position 234 and/or Ala substitution at 235, and/or N297A, and/or a K322A mutation. 35. The fusion construct according to any of the preceding items, wherein said fusion construct comprises a heterodimerization domain. 36. The fusion construct according to any of the preceding items, wherein said heterodimerization domain comprises a sequence according to SEQ ID No.: 48, 49 or 50. 37. The fusion construct according to any of the preceding items, wherein said fusion construct comprises a heterodimerization mutation. 38. The fusion construct according to any of the preceding items, wherein said heterodimerization mutation is an F405L, R409K and/or K409R mutation. 39. The fusion construct according to any of the preceding items, wherein said fusion construct comprises: a. A first chain comprising i. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, and ii. a sequence according to SEQ ID No.: 38, and b. A second chain comprising iii. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, and iv. a sequence according to SEQ ID No.: 38. 40. The fusion construct according to any of the preceding items, wherein said fusion construct comprises: a. A first chain comprising i. a sequence according to SEQ ID No.: 3 or SEQ ID No.: 4, and ii. a sequence according to SEQ ID No.: 38, and b. A second chain comprising iii. a sequence according to SEQ ID No.: 3 or SEQ ID No.: 4, and iv. a sequence according to SEQ ID No.: 38. 41. The fusion construct according to any of the preceding items, wherein said fusion construct comprises: a. A first chain comprising i. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, and ii. a sequence according to SEQ ID No.: 38, and b. A second chain comprising iii. a sequence according to SEQ ID No.: 3 or SEQ ID No.: 4, and iv. a sequence according to SEQ ID No.: 40. 42. The fusion construct according to any of the preceding items, wherein said fusion construct comprises: c. A first chain comprising i. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, and ii. a linker sequence according to SEQ ID No.: 41, and iii. a sequence according to SEQ ID No.: 65 d. A second chain comprising iv. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, and v. a linker sequence according to SEQ ID No.: 41, and vi. a sequence according to SEQ ID No.: 65 43. The fusion construct according to any of the preceding items, wherein said fusion construct comprises: a. A first chain comprising i. a sequence according to SEQ ID No.: 3 or SEQ ID No.:, and ii. a linker sequence according to SEQ ID No.: 41, and iii. a sequence according to SEQ ID No.: 65 b. A second chain comprising iv. a sequence according to SEQ ID No.: 3 or SEQ ID No.: 4, and v. a linker sequence according to SEQ ID No.: 41, and vi. a sequence according to SEQ ID No.: 65 44. The fusion construct according to any of the preceding items, wherein said fusion construct comprises: a. A first chain comprising i. a sequence according to SEQ ID No.: 1 or SEQ ID No.: 2, and ii. a linker sequence according to SEQ ID No.: 41, and iii. a sequence according to SEQ ID No.: 65, wherein said sequence ID No.: 65 comprises one or more of the mutations of table 8 b. A second chain comprising iv. a sequence according to SEQ ID No.: 3 or SEQ ID No.: 4 and v. a linker sequence according to SEQ ID No.: 41, and vi. a sequence according to SEQ ID No.: 65, wherein said sequence ID No.: 65 comprises one or more of the mutations of table 8. 45. The fusion construct according to any of the preceding items, wherein the ratio of fusion construct to said drug and/or payload is selected among 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. 46. The fusion construct according to any of the preceding items, wherein said fusion construct comprises a kappa light chain according to SEQ ID No.: 51 or a lambda light chain according to SEQ ID No.: 52 or 53. 47. A fusion construct, preferably according to any of the preceding items, wherein said fusion construct is an IgG3 construct, and wherein said IgG3 construct comprises a hinge region, wherein said hinge region has been modified. 48. The fusion construct according to any of the preceding items, wherein said hinge region comprises a sequence having a total of at least 10% identity, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% identity to the sequence according to SEQ ID No.: 6 or SEQ ID No.: 8. 49. The fusion construct according to any of the preceding items, wherein said fusion construct comprises the sequence according to SEQ ID No.: 5, 7, 9, 10, 11, 12 and/or 13. 50. The fusion construct according to any of the preceding items, wherein said hinge region comprises at least one free cysteine residue, at least two free cysteine residues or preferably at least three free cysteine residues. 51. The fusion construct according to any of the preceding items, wherein said hinge region comprises a S228P mutation. 52. The fusion construct according to any of the preceding items, wherein said hinge region comprises a sequence according to SEQ ID No.: 6 and/or SEQ ID No.: 8 and/or SEQ ID No.: 68 53. The fusion construct according to any of the preceding items, wherein said fusion construct is used to detect phosphatidylserine. 54. The fusion construct according to any of the preceding items, wherein said fusion construct is used to detect phosphatidylserine in the blood of a subject. 55. The fusion construct according to item 53, wherein said fusion construct comprises a sequence according to SEQ ID No.: 1, and/or a sequence according to SEQ ID No.: 2. 56. The fusion construct according to any of the preceding items, wherein said fusion construct is used to detect C-type lectin binding mannan or fucan moieties. 57. The fusion construct according to any of the preceding items, wherein said fusion construct is used to detect C-type lectin binding mannan or fucan moieties in the blood of a subject. 58. The fusion construct according to item 56, wherein said fusion construct comprises a sequence according to SEQ ID No.: 3 and/or a sequence according to SEQ ID No.: 4. 59. A fusion construct, a fusion protein or an antibody comprising the constant region(s) of IgG3 and a hinge, wherein said hinge preferably is selected among an IgG1 or IgG4 hinge. 60. The fusion construct, fusion protein or antibody according to any of the preceding items, comprising one or more heterodimerization mutations. 61. The fusion construct, fusion protein or antibody according to any of the preceding items, comprising heterodimerization mutations involve positions 405 and/or 409 (EU numbering). 62. IgG3 homodimer comprising a hinge region, wherein said hinge region comprises a sequence selected among SEQ ID No.: 6, 8 and 68. 63. IgG3 heterodimer comprising a hinge region, wherein said hinge region comprises a sequence selected among SEQ ID No.: 6, 8 and 68. 64. IgG3 according to any of the preceding items, wherein said IgG3 comprises a mutation at position 405 and/or position 409. 65. IgM heterodimers obtainable by changing the charge pairs of the CH2 and/or CH4 domains. 66. IgM heterodimers according to any of the preceding items, comprising one or more of the mutations of Table 8. 67. The IgM according to any of the preceding items, wherein said IgM comprises a sequence according to SEQ ID No.: 64 and/or 65. 68. A fusion construct, preferably according to any of the preceding items, wherein said fusion construct comprises an IgG3 homodimer, an IgG3 heterodimer and/or an IgM heterodimer according to any of the preceding items. 69. The fusion construct according to any of the preceding items, wherein said fusion construct is for use in the treatment of an infection. 70. The fusion construct according to any of the preceding items, wherein said infection is an infection caused by a virus, a parasite, a bacteria, a fungi or a protozoan. 71. The fusion construct according to any of the preceding items, wherein said virus is selected among an arborvirus, Zika virus, Dengue virus, West Nile virus, Ebola virus, influenza virus, influenza virus H1N1, Chikungunya virus, enterovirus and Coronaviruses SARS-COV. 72. The fusion construct according to any of the preceding items, wherein said bacteria is selected among Mycobacterium tuberculosis and Mycobacterium leprae. 73. The fusion construct according to any of the preceding items, wherein said parasite is selected among Leishmaniasis and Malaria. 74. Use of a fusion construct according to any of the preceding items for the treatment of an infection. 75. Use according to any of the preceding items, wherein said infections are selected among viral, bacterial and protozoan infections. 76. Use according to any of the preceding items, wherein the treatment comprising administration of the fusion construct with an administration form selected among subcutaneous, intradermal, intramuscular, oral and nasal. 77. Use of IgG4 or a part of IgG4 for payload delivery, wherein said IgG4 has been modified to comprise no Fc or wherein the activity of the Fc of said IgG4 has been nullified or diminished by one or more mutations. 78. The use according to any of the preceding items, wherein said IgG4 comprises one or more heterodimerization mutations. 79. The use according to any of the preceding items, wherein said IgG4 comprises one or more Cys mutations, preferably thereby allowing site specific conjugation. 80. The use according to any of the preceding items, wherein said IgG4 comprises a Cys at position 339 (EU numbering). 81. A vaccine comprising a fusion construct according to any of the preceding items. 82. A vaccine comprising a mannan, a high-mannose containing structure, a fucan and/or a phospholipid phosphatidylserine (PS). 83. The vaccine according to any of the preceding items further comprising β-glucan. 84. The vaccine according to any of the preceding items, for the prevention and/or treatment of an infection. 85. The vaccine according to any of the preceding items, wherein said infection is coursed by a virus, preferably according to item 71, a parasite, preferably according to item 73, a bacteria, preferably according to item 72, a fungi or a protozoan. 86. The fusion construct and/or vaccine according to any of the preceding items, wherein said fusion construct and/or vaccine allows administration through a route selected among subcutaneous administration, intradermal administration, intramuscular administration, oral administration and/or nasal administration. 87. A composition comprising a fusion construct according to any of the preceding items, optionally comprising one or more excipients such as diluents, binders or carriers. 88. A method of treating and/or preventing an infection in a subject, comprising a step of administration of a fusion construct and/or a vaccine and/or a composition according to any of the preceding item. 89. A method of screening and/or monitoring progression of a disease in a subject, wherein said method comprises the following steps: i. Providing a blood sample from said subject. ii. Contacting said blood sample with a fusion construct according to any of the preceding items. 90. An isolated nucleic acid molecule encoding a fusion construct according to any of the precedent items. 91. A recombinant vector comprising the nucleic acid molecule of item 90. 92. A host cell comprising the recombinant vector of item 91. 93. A method for the production of a fusion construct according to any of the precedent items comprising a step of culturing the host cell according to item 92 in a culture medium under conditions allowing the expression of the fusion construct and separating the fusion construct from the culture medium.