Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza hemagglutinin

Abstract

The invention features a novel influenza antibody that specifically binds to influenza hemagglutinin and reduces or inhibits hemagglutinin binding to sialic acid. The invention also provides methods, compositions, and kits featuring the novel antibody and its use in preventing or treating influenza infection.

1 .- 33 . (canceled) 
     
     
         34 . A method of treating or preventing an influenza virus infection in a subject in need thereof, wherein the method comprises administering to the subject an effective amount of i) an anti-influenza antibody or antibody fragment that specifically binds influenza hemagglutinin (HA) at residues 136, 137 and 226 of the HA polypeptide sequence and thereby reduces or inhibits influenza hemagglutinin binding to sialic acid, wherein the anti-influenza antibody or antibody fragment comprises at least one sequence selected from the group consisting of:
 a variable heavy (V H ) chain sequence SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, or one or more heavy chain CDR regions present in a variable heavy (V H ) chain amino acid sequence of SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, or SEQ ID NO: 12; and   a variable light (V L ) chain sequence SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, or one or more light chain CDR regions present in a variable light (V L ) chain amino acid sequence of SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, or SEQ ID NO: 16   
       or ii) a pharmaceutical composition comprising said anti-influenza antibody or antibody fragment, thereby treating or preventing influenza virus infection in the subject. 
     
     
         35 .- 38 . (canceled) 
     
     
         39 . The method of  claim 34 , wherein the influenza is H1N1, H2N2, H3N2, or a human adapted H5 strain. 
     
     
         40 . The method of  claim 34 , wherein the subject has or is at risk of developing an influenza infection. 
     
     
         41 . The method of  claim 40 , wherein the subject is a mammal. 
     
     
         42 . The method of  claim 41 , wherein the subject is human. 
     
     
         43 . The method of  claim 40 , wherein the subject is susceptible to viral infection. 
     
     
         44 . The method of  claim 43 , wherein the subject is a pregnant female. 
     
     
         45 . The method of  claim 43 , wherein the subject is a young subject or an infant subject. 
     
     
         46 . The method of  claim 43 , wherein the subject is an elderly subject. 
     
     
         47 . The method of  claim 34 , wherein i) the anti-influenza antibody or antibody fragment, or ii) the pharmaceutical composition is administered by intramuscular injection, intravenous injection, subcutaneous injection, or inhalation. 
     
     
         48 .- 58 . (canceled) 
     
     
         59 . An anti-influenza Fab that specifically binds influenza hemagglutinin (HA) at residues 136, 137 and 226 of the HA polypeptide sequence and thereby reduces or inhibits influenza hemagglutinin binding to sialic acid. 
     
     
         60 . The anti-influenza Fab of  claim 59 , wherein the HA polypeptide sequence is selected from the group consisting of SEQ ID NOS: 17-44. 
     
     
         61 . The anti-influenza Fab of  claim 59 , wherein the HA is selected from the group consisting of H1 HA, H2 HA, H3 HA, or H5 HA. 
     
     
         62 . The anti-influenza Fab of  claim 61 , wherein the Fab further binds HA at one or more HA residues selected from the group consisting of: HA residues 158-160; HA residues 190-195; HA residues 222, 225, and 227; and A/Solomon Islands/3/2006 HA residues 187 and 189. 
     
     
         63 . The anti-influenza Fab of  claim 62 , wherein the Fab further contacts an HA residue selected from the group consisting of HA residues 190-195. 
     
     
         64 . The anti-influenza Fab of  claim 61 , wherein the antibody complementary determining region (CDR) H1 region contacts HA residue 158; the CDR H2 region contacts HA residues 158-160; the CDR H3 region contacts HA residues 135-136, 190-194 and 226; the CDR L1 region contacts HA residues 222, 225 and 227; or the CDR L3 region contacts HA residues 187 and 198.