Compositions and methods for the therapy and diagnosis of influenza
The present invention provides compositions, vaccines, and methods for diagnosing, treating, and preventing influenza infection using a combination of antibodies raised against the influenza hemagglutinin and the matrix 2 ectodomain polypeptides.
1. A composition comprising:
(a) an isolated human monoclonal antibody that specifically binds to an epitope of the hemagglutinin (HA) glycoprotein of an influenza virus, wherein said antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 435 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 438; and
(b) an isolated human monoclonal antibody that specifically binds to an epitope in the extracellular domain of the matrix 2 ectodomain (M2e) polypeptide of an influenza virus, wherein said antibody comprises a V H CDR1 region comprising the amino acid sequence of NYYWS (SEQ ID NO: 72); a V H CDR2 region comprising the amino acid sequence of FIYYGGNTKYNPSLKS (SEQ ID NO: 74); a V H CDR3 region comprising the amino acid sequence of ASCSGGYCILD (SEQ ID NO: 76); a V L CDR1 region comprising the amino acid sequence of RASQNIYKYLN (SEQ ID NO: 59); a V L CDR2 region comprising the amino acid sequence of AASGLQS (SEQ ID NO: 61); a V L CDR3 region comprising the amino acid sequence of and QQSYSPPLT (SEQ ID NO: 63), and wherein said epitope of the M2e polypeptide is a discontinuous epitope.
2. The composition of claim 1 , wherein said epitope of the HA glycoprotein is GVTNKVNSIIDK (SEQ ID NO: 198).
3. The composition of claim 1 , wherein said epitope of the M2e polypeptide includes the amino acid at positions 2, 5, and 6 of MSLLTEVETPTRNEWGCRCNDSSD (SEQ ID NO: 1).
4. A passive immunization composition comprising the composition of claim 1 .
5. A pharmaceutical composition comprising the composition of claim 1 and a pharmaceutical carrier.
6. A method for the treatment of an influenza virus infection in a subject in need thereof, comprising administering to the composition of claim 5 .
7. The method of claim 6 , wherein the subject has been exposed to an influenza virus.
8. The method of claim 6 , wherein the method further comprises administering an anti-viral drug, a viral entry inhibitor or a viral attachment inhibitor.
9. The method of claim 8 , wherein said anti-viral drug is a neuraminidase inhibitor, a HA inhibitor, a sialic acid inhibitor or an M2 ion channel.
10. The method of claim 9 , wherein said M2 ion channel inhibitor is amantadine or rimantadine.
11. The method of claim 9 , wherein said neuraminidase inhibitor is zanamivir or oseltamivir phosphate.
12. The method of claim 6 , further comprising administering a third anti-Influenza A antibody.
13. A diagnostic kit comprising the composition of claim 1 .
14. A prophylactic kit comprising the composition according to claim 4 .