Human monoclonal antibodies to a new universal influenza A hemagglutinin head domain epitope
The present disclosure is directed to antibodies binding previously undefined epitopes on influenza A virus hemagglutinin and methods for use thereof.
1. A method of treating a subject infected with influenza A virus or reducing the likelihood of infection of a subject at risk of contracting influenza A virus, comprising administering to said subject an antibody or antibody fragment having heavy chain CDR1-3 sequences and light chain CDR1-3 sequences of SEQ ID NOS: 17-19 and SEQ ID NOS: 29-31, respectively, or administering an RNA or DNA sequence or vector encoding the antibody or antibody fragment.
2. The method of claim 1 , the antibody or antibody fragment is encoded by light and heavy chain variable sequences of SEQ ID NOS: 2 and 1, respectively.
3. The method of claim 1 , the antibody or antibody fragment is encoded by light and heavy chain variable sequences having 95% identity to SEQ ID NOS: 2 and 1, respectively.
4. The method of claim 1 , wherein said antibody or antibody fragment is encoded by light and heavy chain variable sequences having 70%, 80%, or 90% identity to SEQ ID NOS: 2 and 1, respectively.
5. The method of claim 1 , wherein said antibody or antibody fragment comprises light and heavy chain variable sequences according to sequences of SEQ ID NOS: 10 and 9, respectively.
6. The method of claim 1 , wherein said antibody or antibody fragment comprises light and heavy chain variable sequences having 70%, 80% or 90% identity to SEQ ID NOS: 10 and 9, respectively.
7. The method of claim 1 , wherein said antibody or antibody fragment comprises light and heavy chain variable sequences having 95% identity to SEQ ID NOS: 10 and 9, respectively.
8. The method of claim 1 , wherein the antibody fragment is a recombinant scFv (single chain fragment variable) antibody, Fab fragment, F(ab′) 2 fragment, or Fv fragment.
9. The method of claim 1 , wherein said antibody is an IgG, or a recombinant IgG antibody or antibody fragment that comprises an Fc portion mutated to eliminate or enhance FcR interactions, to increase half-life and/or increase therapeutic efficacy, or comprises a glycan modification to eliminate or enhance FcR interactions.
10. The method of claim 1 , wherein said antibody is a chimeric antibody or a bispecific antibody.
11. The method of claim 1 , wherein said antibody or antibody fragment is administered prior to infection or after infection.
12. The method of claim 1 , wherein said subject is a pregnant female, a sexually active female, or a female undergoing fertility treatments.
13. The method of claim 1 , wherein delivering comprises antibody or antibody fragment administration, or genetic delivery with an RNA or DNA sequence or vector encoding the antibody or antibody fragment.
14. The method of claim 1 , wherein said antibody or antibody fragment has an antiviral molecule attached thereto.
15. The method of claim 9 , wherein the mutation to eliminate or enhance FcR interactions, to increase half-life and/or increase therapeutic efficacy is a LALA, N297, GASD/ALIE, YTE or LS mutation.
16. The method of claim 9 , wherein said glycan modification is a result of enzymatic or chemical addition or removal of glycans, or expression in a cell line engineered with a defined glycosylating pattern.