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 anti-matrix 2 ectodomain (M2e) antibody, or antigen-binding fragment thereof, comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain and the VL domain each comprise three complementarity determining regions 1 to 3 (CDR1-3), and wherein each CDR comprises the following amino acid sequences:
VH CDR1: SEQ ID NOs: 179, 187, 196, 204, 212, 224, 230, 235, 242, 248, or 254;
VH CDR2: SEQ ID NOs: 180, 188, 195, 197, 205, 213, 218, 225, 231, 236, 243, 249, 246, or 256;
VH CDR3 SEQ ID NOs: 181, 189, 198, 206, 214, 219, 226, 232, 237, 244, or 250;
VL CDR1: SEQ ID NOs: 184, 192, 199, 215, 220, 233, or 238;
VL CDR2: SEQ ID NOs: 61, 185, 193, 200, 207, 211, 216, 227, 239, or 241; and
VL CDR3: SEQ ID NOs: 63, 186, 194, 201, 208, 221, 228, 234, 240, 245, or 251; or wherein each CDR comprises the following amino acid sequences:
VH CDR1: SEQ ID NOs: 182, 190, 202, 209, 222, 229, 247, 252, 257, 258, or 260;
VH CDR2: SEQ ID NOs: 183, 191, 203, 210, 217, 223, 230, 246, 253, 259, or 261;
VH CDR3 SEQ ID NOs: 181, 189, 195, 198, 206, 214, 219, 226, 232, 237, 244, or 250;
VL CDR1: SEQ ID NOs: 184, 192, 199, 215, 220, 233, or 238;
VL CDR2: SEQ ID NOs: 61, 185, 193, 200, 207, 211, 216, 227, 239, or 241; and
VL CDR3: SEQ ID NOs: 63, 186, 194, 201, 208, 221, 228, 234, 240, 245, or 251.
2 . A pharmaceutical composition comprising any one of the antibodies of claim 1 and a pharmaceutical carrier.
3 . An antibody that binds the same epitope as any one of the antibodies of claim 1 .
4 . The composition of claim 2 , further comprising an anti-viral drug, a viral entry inhibitor or a viral attachment inhibitor.
5 . The composition of claim 4 , wherein said anti-viral drug is a neuraminidase inhibitor, a HA inhibitor, a sialic acid inhibitor or an M2 ion channel inhibitor.
6 . The method of claim 5 , wherein said M2 ion channel inhibitor is amantadine or rimantadine.
7 . The method of claim 5 , wherein said neuraminidase inhibitor zanamivir or oseltamivir phosphate.
8 . The composition of claim 2 , further comprising a second anti-influenza A antibody.
9 . A method for stimulating an immune response in a subject, comprising administering to the patient the composition of claim 2 .
10 . A method for the treatment or prevention of an influenza virus infection in a subject, comprising administering to the subject the composition of claim 2 .
11 . The method of claim 10 , wherein the method further comprises administering an anti-viral drug, a viral entry inhibitor or a viral attachment inhibitor.
12 . The method of claim 11 , wherein said anti-viral drug is a neuraminidase inhibitor, a HA inhibitor, a sialic acid inhibitor or an M2 ion channel.
13 . The method of claim 12 , wherein said M2 ion channel inhibitor is amantadine or rimantadine.
14 . The method of claim 12 , wherein said neuraminidase inhibitor zanamivir or oseltamivir phosphate.
15 . The method of claim 10 , wherein said composition is administered prior to or after exposure to influenza virus.
16 . The method of claim 10 , wherein said composition is administered at a dose sufficient to promote viral clearance or eliminate influenza A infected cells.
17 . A method for determining the presence of a influenza virus infection in a patient, comprising the steps of:
(a) contacting a biological sample obtained from the patient with the antibody of claim 1 ;
(b) detecting an amount of the antibody that binds to the biological sample; and
(c) comparing the amount of antibody that binds to the biological sample to a control value, and therefrom determining the presence of the influenza virus in the patient.
18 . A diagnostic kit comprising the antibody of claim 1 .