Influenza A virus group 2 hemagglutinin (Group 2 HA)

Influenza A virus group 2 hemagglutinin (HA) is a major surface glycoprotein on Influenza A viruses belonging to the Group 2 phylogenetic lineage, which includes the H3, H4, H7, H10, H14, and H15 subtypes (Source: UniProt). It is a class I fusion protein that exists as a homotrimer, where each monomer is composed of the HA1 subunit for receptor binding and the HA2 subunit for membrane fusion (Source: PubMed PMC3530501). The protein is essential for viral entry, as it mediates the attachment of the virus to sialic acid receptors on the host cell surface and facilitates the fusion of the viral envelope with the endosomal membrane under acidic conditions. Because Group 2 viruses, particularly H3N2, are major drivers of seasonal influenza epidemics and possess pandemic potential, this protein is a primary target for vaccines and therapeutic antibodies. CF-402 is an investigational monoclonal antibody that specifically targets a highly conserved epitope on the Group 2 hemagglutinin (Source: ContraFect Corp). Unlike traditional vaccines that target the highly variable head region of HA, CF-402 is designed to bind to more stable regions, such as the stalk, to provide broad-spectrum neutralization across multiple Group 2 subtypes. By binding to these sites, the antibody prevents the structural rearrangements of the HA protein necessary for the fusion of the viral and host membranes, thereby blocking the infection process. This approach aims to overcome the challenges of antigenic drift, which frequently renders seasonal influenza vaccines and strain-specific antibodies ineffective.

Other names

Group 2 HAInfluenza A HA Group 2H3-clade hemagglutininInfluenza A virus group 2 hemagglutinin – CF-402

Neutralization of viral activity by binding to the hemagglutinin protein, thereby blocking host cell attachment or preventing the pH-triggered conformational change required for membrane fusion (Source: PubMed PMC4776122).