HLA binding vaccine moieties and uses thereof
View Patent ↗The present invention relates to an immunoglobulin derived single-chain fragment variable (scFv) that broadly binds HLA II molecules and uses thereof. In particular, targeting of an antigen to antigen presenting cells with the HLAII-specific targeting unit provided herein find use in enhancing immune responses after vaccination.
1. A nucleic acid comprising a sequence encoding an antibody, a scFv or a Fab fragment comprising light chain complementarity determining region (LCDR) 1 of SEQ ID NO:4; LCDR 2 of SEQ ID NO:5; and LCDR 3 of SEQ ID NO:6; and heavy chain complementarity determining region (HCDR) 1 of SEQ ID NO:7; HCDR 2 of SEQ ID NO:8 and; HDCR 3 of SEQ ID NO:9.
2. The nucleic acid of claim 1 , further comprising a sequence encoding an antigen.
3. The nucleic acid of claim 1 , further comprising a sequence encoding at least two distinct antigens.
4. The nucleic acid of claim 2 , wherein antigen is derived from a pathogenic microorganism.
5. The nucleic acid of claim 4 , wherein said pathogenic microorganism is influenza virus or Ebola virus.
6. The nucleic acid of claim 2 , wherein said nucleic acid further comprises a linker sequence between said sequence encoding an antigen and said nucleic acid comprising a sequence encoding an antibody, a scFv or a Fab fragment.
7. The nucleic acid of claim 6 , wherein said linker comprises a dimerization unit comprising a hinge region from an immunoglobulin and an immunoglobulin constant region.
8. The nucleic acid of claim 7 , wherein said linker is a dimerization unit derived from a natural protein.
9. A pharmaceutical composition, comprising: the nucleic acid of claim 1 and a pharmaceutically acceptable carrier.
10. The composition of claim 9 , wherein said composition further comprises an adjuvant.
11. The nucleic acid of claim 1 , wherein the nucleic acid encodes the polypeptide of SEQ ID NO:1.
12. The nucleic acid of claim 4 , wherein said pathogenic microorganism is selected from the group consisting of orthomyxoviruses, paramyxoviruses, adenoviruses, rhinoviruses, coronaviruses, reoviruses, togaviruses, parvoviruses, poxviruses, enteroviruses, hepatitis viruses, herpesviruses, rotaviruses, Norwalk viruses, hantavirus, arenavirus, rhabdovirus, retroviruses, papovaviruses, polyomaviruses, picornaviruses, Dengue virus, Filoviruses, Hantavirus, Rift Valley virus, HHV-8, Human papillomavirus, Bovine leukemia virus, Influenza virus, Guanarito virus, Lassa virus, Measles virus, Rubella virus, Mumps virus, Chickenpox, Monkey pox, Epstein Bahr virus, Parvovirus B 19, Hantaan virus, Sin Nombre virus, Venezuelan equine encephalitis, Sabia virus, West Nile virus and Yellow Fever virus.