Influenza treatment and/or characterization, human-adapted ha polypeptides; vaccines

Abstract

The present invention provides, among other things, methods, reagents, and systems for the treatment, detection, analysis, and/or characterization of influenza infections.

1 - 29 . (canceled) 
     
     
         30 . A method of treating influenza infection by administering a composition comprising an engineered HA polypeptide that possesses at least 90% overall sequence identity with a reference HA polypeptide of SEQ ID NO:1, which engineered HA polypeptide characterized in that its amino acid sequence includes:
 an amino acid residue (“Residue 137”) at a position corresponding to position 137 of SEQ ID NO:1 that is selected from the group consisting of arginine, lysine, glutamine, methionine and histidine; and   an amino acid residue (“Residue 193”) at a position corresponding to position 193 of SEQ ID NO:1 that is selected from the group consisting of alanine, aspartic acid, glutamic acid, leucine, isoleucine, methionine, serine, threonine, cysteine, and valine; and   an amino acid residue (“Residue 226”) at a position corresponding to position 226 of SEQ ID NO:1 that is selected from the group consisting of alanine, cysteine, glycine, isoleucine, leucine, methionine, phenylalanine, proline, tryptophan and valine; and   an amino acid residue (“Residue 228”) at a position corresponding to position 228 of SEQ ID NO:1 that is selected from the group consisting of arginine, asparagine, aspartic acid, glutamic acid, glutamine, histidine, lysine, serine, glycine, threonine, and tyrosine.   
     
     
         31 . A vaccine composition comprising an engineered HA polypeptide of  claim 30 . 
     
     
         32 . The vaccine composition of  claim 31 , wherein the vaccine composition comprises a live attenuated virus. 
     
     
         33 . The vaccine composition of  claim 31 , wherein the vaccine composition comprises virus-like particles. 
     
     
         34 . The vaccine composition of  claim 31 , wherein the vaccine composition is a subunit vaccine. 
     
     
         35 . The vaccine composition of  claim 31 , further comprising an adjuvant. 
     
     
         36 . A method comprising administering the vaccine composition of  claim 31  to an individual suffering from or susceptible to influenza virus infection. 
     
     
         37 . A method of identifying or characterizing binding agents, the method comprising contacting the binding agents with an HA polypeptide that possesses at least 90% overall sequence identity with a reference HA polypeptide of SEQ ID NO:1, which engineered HA polypeptide characterized in that its amino acid sequence includes:
 an amino acid residue (“residue 137”) at a position corresponding to position 137 of SEQ ID NO:1 that is selected from the group consisting of arginine, lysine, glutamine, methionine and histidine; and   an amino acid residue (“residue 193”) at a position corresponding to position 193 of SEQ ID NO:1 that is selected from the group consisting of alanine, aspartic acid, glutamic acid, leucine, isoleucine, methionine, serine, threonine, cysteine, and valine; and   an amino acid residue (“residue 226”) at a position corresponding to position 226 of SEQ ID NO:1 that is selected from the group consisting of alanine, cysteine, glycine, isoleucine, leucine, methionine, phenylalanine, proline, tryptophan and valine; and   an amino acid residue (“residue 228”) at a position corresponding to position 228 of SEQ ID NO:1 that is selected from the group consisting of arginine, asparagine, aspartic acid, glutamic acid, glutamine, histidine, lysine, serine, glycine, threonine, and tyrosine; and   assessing binding therebetween.