Hemagglutinin polypeptides, and reagents and methods relating thereto

Abstract

The present invention provides a system for analyzing interactions between glycans and interaction partners that bind to them. The present invention also provides HA polypeptides that bind to umbrella-topology glycans, and reagents and methods relating thereto.

1 .- 20 . (canceled) 
     
     
         21 . A method of inhibiting binding of a H5 influenza virus to a hemagglutinin receptor having an umbrella topology, in a subject, or minimizing the risk of infection of a subject by an influenza virus which binds a hemagglutinin receptor having an umbrella topology, or treating a subject, the method comprising:
 identifying a subject susceptible to or suffering from infection by an influenza virus,   selecting a binding agent that competes a glycan HA polypeptide interaction between an umbrella topology glycan and an HA polypeptide; and   
       administering an effective amount of the binding agent so that binding by the virus to hemagglutinin receptors having umbrella topology glycans is reduced, the risk is minimized, or the patient is treated. 
     
     
         22 . The method of  claim 21 , wherein the binding agent comprises an H5 HA polypeptide sequence from a reference H5 HA polypeptide sequence at one or more of residues selected from the group consisting of residues 130, 131, 132, 133, 135, 137, 155, 188, 192, 193, 221, 226, 227, 228, and combinations thereof. 
     
     
         23 . The method of  claim 21 , wherein the step of selecting includes selecting a binding agent on the basis of the binding agent being able to bind a hemagglutinin receptor having umbrella topology glycans. 
     
     
         24 . The method of  claim 21 , wherein the binding agent is an LSBA. 
     
     
         25 . The method of  claim 21 , wherein the binding agent is a UTBA. 
     
     
         26 . The method of  claim 21 , wherein the binding agent is a UTSBA. 
     
     
         27 . The method of  claim 26 , wherein the UTSBA is administered to the subject prior to exposure to the virus. 
     
     
         28 . The method of  claim 26 , wherein the UTSBA is administered to the subject after exposure to the virus. 
     
     
         29 . The method of  claim 21 , wherein amount administered is sufficient to saturate the subject's HA receptors containing umbrella topology glycans. 
     
     
         30 . The method of  claim 26 , wherein the UTSBA is administered by inhalation. 
     
     
         31 . The method of  claim 26 , wherein the UTSBA is selected from the group consisting of antibodies, lectins, aptamers, and non-HA polypeptides. 
     
     
         32 . The method of  claim 26 , wherein said UTSBA is administered in combination with administration of a second therapeutic. 
     
     
         33 . The method of  claim 32 , wherein the second therapeutic is an anti-viral agent.