Influenza hemagglutinin stalk region (HA stalk)

The Influenza hemagglutinin stalk region is a highly conserved structural component of the hemagglutinin (HA) glycoprotein, the primary surface antigen of the influenza virus. While the HA head domain undergoes frequent antigenic drift to evade the immune system, the stalk region—comprising the HA2 subunit and portions of HA1—remains relatively invariant across diverse influenza subtypes (Corti & Lanzavecchia, 2013). This high level of conservation makes the stalk a premier target for the development of universal influenza vaccines and broadly neutralizing antibodies (bnAbs) intended to provide protection against seasonal and pandemic strains (Krammer & Palese, 2013). Biologically, the stalk region mediates the critical step of membrane fusion between the viral envelope and the host cell endosome, a process triggered by the acidic environment of the endocytic pathway (Impagliazzo et al., 2015). Therapeutic agents, including monoclonal antibodies like MEDI8852 and small molecules like JNJ-4796, function by binding to this region and stabilizing the pre-fusion state of the protein (van Dongen et al., 2019). By physically blocking the conformational rearrangements necessary for fusion, these inhibitors prevent the release of the viral genome into the host cell, effectively neutralizing the virus across multiple lineages.

Other names

Hemagglutinin stem domainHA stemHA2 subunitConserved stalk regionHemagglutinin fusion domain

Binding to the conserved stalk region prevents the pH-triggered conformational change of hemagglutinin, thereby inhibiting the fusion of the viral envelope with the host endosomal membrane and blocking viral genome release into the cytoplasm.