Antibodies useful in passive influenza immunization, and compositions, combinations and methods for use thereof
Antibodies, compositions and methods are provided for treatment and prophylaxis of influenza virus. Antibodies and antigen-binding fragments are provided that bind near the HA 0 maturation cleavage site consensus sequence of influenza hemagglutinin A. Antibody compositions, combinations and methods for effective passive immunization across influenza A and B strains are also provided.
1. An isolated human antibody, or antigen-binding fragment thereof that exhibits a binding affinity (KD) of 10 nM or tighter, or 3 nM or tighter, to one or more strains of each of influenza B Yamagata and influenza B Victoria clades, the antibody or fragment comprising (a) a heavy chain complementarity determining region 1 (HCDR1), (b) a heavy chain complementarity determining region 2 (HCDR2); and (c) a heavy chain complementarity determining region 3 (HCDR3), HCDR1/HCDR2/HCDR3, having SEQ ID NO: 241/242/243; and (d) a light chain complementarity determining region 1 (LCDR1), (e) a light chain complementarity determining region 2 (LCDR2), and (f) a light chain complementarity determining region 3 (LCDR3), LCDR1/LCDR2/LCDR3, having SEQ ID NO: 244/245/246, said antibody or fragment having the property of binding to and/or inhibiting influenza virus.
2. An isolated human antibody or antigen binding-fragment thereof that specifically binds to one or more strains of each of both influenza B Yamagata and influenza B Victoria clades and comprises a heavy chain variable region (HCVR)/light chain variable region (LCVR) sequence pair having SEQ ID NO: 249/250, said antibody or fragment having the property of binding to and/or inhibiting influenza virus.
3. An isolated human antibody or antigen binding-fragment thereof that specifically binds to one or more strains of each of influenza B Yamagata and influenza B Victoria clades and comprises an HC/LC sequence pair having SEQ ID NO: 247/248, said antibody or fragment having the property of binding to and/or inhibiting influenza virus.
4. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 1 and a pharmaceutically acceptable carrier.
5. The pharmaceutical composition according to claim 4 , wherein said antibody or fragment exhibits a first melting temperature (Tm1) as measured in PBS of greater than or equal to 55° C.
6. The pharmaceutical composition according to claim 5 , further comprising one or more human antibodies or antigen-binding fragments thereof with binding specificity to at least one strain of influenza A.
7. The pharmaceutical composition according to claim 6 , wherein the antibody or antigen-binding fragment with specificity to influenza A includes specificity to one or more strains of both Group 1 and Group 2.
8. The antibody or antigen-binding fragment of claim 1 , that is a recombinant antibody or fragment thereof.