Human binding molecules capable of binding to and neutralizing influenza b viruses and uses thereof

Abstract

Described are binding molecules, such as human monoclonal antibodies, that bind to hemagglutinin of influenza B viruses, and have a broad neutralizing activity against such influenza viruses. These binding molecules do not bind to hemagglutinin of influenza A viruses. Further provided are nucleic acid molecules encoding the binding molecules, and compositions comprising the binding molecules. The binding molecules can be used in the diagnosis of, prophylaxis against, and/or treatment of influenza B virus infections.

1 . A binding molecule able to:
 specifically bind to hemagglutinin (HA) of influenza B virus strains of the B/Yamagata and B/Victoria lineage, and   neutralize the influenza B virus strains of the B/Yamagata and/or B/Victoria lineage,   wherein the binding molecule does not bind to HA of influenza A viruses.   
     
     
         2 . The binding molecule of  claim 1 , which binds to the head region of HA of influenza B virus. 
     
     
         3 . The binding molecule of  claim 2 , wherein the binding molecule comprises a heavy chain variable region comprising SEQ ID NO:71 or a peptide having at least about 80% sequence identity thereto. 
     
     
         4 . The binding molecule of  claim 3 , wherein the binding molecule comprises a light chain variable region comprising SEQ ID NO:73, or a peptide having at least about 80% sequence identity thereto. 
     
     
         5 . The binding molecule of  claim 4 , wherein the binding molecule comprises a heavy chain variable region comprising SEQ ID NO:71 and a light chain variable region comprising SEQ ID NO:73. 
     
     
         6 . The binding molecule of  claim 2 , wherein the binding molecule comprises a heavy chain variable region comprising SEQ ID NO:75, or a peptide having at least or at least about 80% sequence identity thereto. 
     
     
         7 . The binding molecule of  claim 6 , wherein the binding molecule comprises a light chain variable region comprising SEQ ID NO:77, or a peptide having at least about 80% sequence identity thereto. 
     
     
         8 . The binding molecule of  claim 7 , wherein the binding molecule comprises:
 a heavy chain variable region comprising SEQ ID NO:75, and   a light chain variable region comprising SEQ ID NO:77.   
     
     
         9 . The binding molecule of  claim 7 , wherein the binding molecule comprises:
 a heavy chain variable region consisting of SEQ ID NO:78, and   a light chain variable region consisting of SEQ ID NO:79.   
     
     
         10 . The binding molecule of  claim 2 , wherein the binding molecule comprises a heavy chain variable region comprising SEQ ID NO:113 or a peptide having at least about 80% sequence identity thereto. 
     
     
         11 . The binding molecule of  claim 10 , wherein the binding molecule comprises a light chain variable region comprising SEQ ID NO:115, or a peptide having at least about 80% sequence identity thereto. 
     
     
         12 . The binding molecule of  claim 11 , wherein the binding molecule comprises:
 a heavy chain variable region comprising SEQ ID NO:113, and   a light chain variable region comprising SEQ ID NO:115.   
     
     
         13 . A binding molecule that immunospecifically competes for binding to an epitope on an influenza B virus HA protein with the binding molecule of  claim 1 . 
     
     
         14 . The binding molecule of  claim 1 , wherein the binding molecule inhibits egress of influenza B virus from a cell infected therewith. 
     
     
         15 . The binding molecule of  claim 1 , wherein the binding molecule is isolated, monoclonal, a human monoclonal antibody, and/or an antigen-binding fragment of a human monoclonal antibody. 
     
     
         16 . An immunoconjugate comprising:
 at least one binding molecule of  claim 1 , and   at least one tag.   
     
     
         17 . A polynucleotide encoding the binding molecule of  claim 1 . 
     
     
         18 . A pharmaceutical composition comprising:
 the binding molecule of  claim 1 , and   a pharmaceutically acceptable carrier or excipient.   
     
     
         19 . A pharmaceutical composition comprising:
 the immunoconjugate of  claim 16 , and   a pharmaceutically acceptable carrier or excipient.   
     
     
         20 . A pharmaceutical composition comprising:
 the polynucleotide of  claim 17 , and   a pharmaceutically acceptable carrier or excipient.   
     
     
         21 . A method of detecting an influenza B virus infection in a subject, the method comprising:
 assaying the level of influenza B virus antigen in a biological sample of the subject utilizing the binding molecule of  claim 1 ; and   comparing the assayed level of influenza B virus antigen in the biological sample with a control level, wherein an increase in the assayed level of influenza B virus antigen compared to the control level of the influenza B virus antigen is indicative of an influenza B virus infection in the subject.   
     
     
         22 . The method according to  claim 21 , wherein when the assayed level indicates influenza B infection, the subject is treated for influenza B infection. 
     
     
         23 . The binding molecule of  claim 2 , which binds to the head region of HA1 of an influenza B virus. 
     
     
         24 . A method of diagnosing, prophylaxing against, and/or treating an influenza infection caused by influenza B virus in a subject, the method comprising:
 utilizing the pharmaceutical composition of  claim 18  to diagnose, prophylax against, and/or treat the influenza infection in the subject.