Compositions and methods for the therapy and diagnosis of influenza
The present invention provides novel human anti-influenza antibodies and related compositions and methods. These antibodies are used in the diagnosis and treatment of influenza infection.
1. An isolated fully human monoclonal antibody, wherein said monoclonal antibody has the following characteristics
a) binds to an epitope in the extracellular domain of the matrix 2 ectodomain (M2e) polypeptide of an influenza A virus;
b) binds to influenza A infected cells; and
c) binds to influenza A virus, and wherein said antibody comprises a V H CDR1 comprising the amino acid sequence of SNYMS (SEQ ID NO: 103); a V H CDR2 region comprising amino acid sequence of VIYSGGSTYYADSVK (SEQ ID NO: 105), a V H CDR3 region comprising the amino acid sequence of CLSRMRGYGLDV (SEQ ID NO: 107); a V L CDR1 region comprising the amino acid sequence of RTSQSISSYLN (SEQ ID NO: 92); a V L CDR2 region comprising the amino acid sequence of AASSLQSGVPSRF (SEQ ID NO: 94); and a V L CDR3 region comprising the amino acid sequence of QQSYSMPA (SEQ ID NO: 96).
2. An isolated anti-matrix 2 ectodomain (M2e) antibody, wherein said antibody comprises a V H CDR1 region comprising the amino acid sequence of SNYMS (SEQ ID NO: 103); a V H CDR2 region comprising the amino acid sequence of VIYSGGSTYYADSVK (SEQ ID NO: 105), a V H CDR3 region comprising the amino acid sequence of CLSRMRGYGLDV (SEQ ID NO: 107); a V L CDR1 region comprising the amino acid sequence of RTSQSISSYLN (SEQ ID NO: 92); a V L CDR2 region comprising the amino acid sequence of AASSLQSGVPSRF (SEQ ID NO: 94); and a V L CDR3 region comprising the amino acid sequence of QQSYSMPA (SEQ ID NO: 96); wherein the M2e is of an influenza A virus.
3. An isolated fully human monoclonal anti-matrix 2 ectodomain (M2e) antibody comprising
a heavy chain sequence comprising the amino acid sequence of SEQ ID NO: 50 and a light chain sequence comprising the amino acid sequence SEQ ID NO: 52; wherein the M2e is of an influenza A virus.
4. A composition comprising the antibody of claim 1 .
5. The composition of claim 4 , further comprising an anti-viral drug, a viral entry inhibitor or a viral attachment inhibitor.
6. The composition of claim 5 , wherein said anti-viral drug is a neuraminidase inhibitor, a HA inhibitor, a sialic acid inhibitor or an M2 ion channel inhibitor.
7. The composition of claim 6 , wherein said neuraminidase inhibitor is zanamivir, or oseltamivir phosphate.
8. The composition of claim 4 , further comprising a second anti-influenza A antibody.
9. The antibody of claim 1 , wherein said antibody is operably-linked to a therapeutic agent or a detectable label.
10. A diagnostic kit comprising the antibody according to claim 1 .