Influenza A and B virus hemagglutinin (HA)

Influenza A and B virus hemagglutinin (HA) is a trimeric glycoprotein found on the surface of influenza viruses and is essential for viral infectivity[1][5][6]. HA mediates attachment of the virus to host cells by binding to sialic acid-containing receptors, determining host specificity and cell tropism[5][6]. After endocytosis into the host cell, the acidic environment of the endosome triggers HA to undergo a dramatic conformational change, allowing it to facilitate fusion of the viral and host membranes and enabling viral genome delivery into the cytoplasm[1][6][7]. HA is the principal target of neutralizing antibodies following natural infection or vaccination, which justifies its role as a major therapeutic and vaccine target[5][6][7]. Antibody recognition is usually strain- or subtype-specific due to antigenic variation, but some broadly neutralizing antibodies target conserved HA regions. HA exists in multiple antigenic subtypes (e.g., H1–H16 for influenza A), which pair with various neuraminidase (NA) subtypes to define influenza strains; this diversity underpins the capacity for pandemics and the need for ongoing vaccine reformulation[1][7][5]. Despite successful targeting, challenges remain due to rapid HA evolution and immune escape, and a universal influenza vaccine remains a major goal of research. HA can be detected and measured as a biomarker for infection and immune status (hemagglutination inhibition). HA is not directly targeted by traditional neuraminidase inhibitors but is the target for neutralizing antibodies, monoclonal biologics, and various experimental entry inhibitors[6][5]. Safety considerations include the risk of rapid antigenic variation, which allows escape from immunotherapy or incomplete vaccine protection[5].

Other names

Influenza hemagglutininHemagglutinin proteinHA proteinInfluenza virus HA

Inhibition of viral entry by blocking attachment to sialic acid receptors (antibodies, entry inhibitors)[6][1][5]. Inhibition of HA-mediated membrane fusion Antibody-mediated neutralization by binding the HA head (blocks receptor binding) or stem (blocks fusion and viral entry)[5]. Immune-mediated clearance via ADCC or CDC when antibodies are bound to HA