Influenza A virus group 2 haemagglutinin stem region (HA stem (Group 2))

The haemagglutinin (HA) stem region of group 2 influenza A viruses is a highly conserved structural domain located on the surface of the influenza virus. While the globular head of the HA protein frequently mutates to evade the host immune system, the stem region remains relatively stable across different Group 2 subtypes, including H3, H4, H7, H10, H14, and H15 (Ekiert et al., Science, 2011). This conservation makes it a premier target for the development of universal influenza vaccines and broadly neutralizing monoclonal antibodies (bnAbs). Biologically, the HA stem is a Class I fusion protein that mediates the critical step of merging the viral envelope with the host endosomal membrane (Harrison, Nature Reviews Microbiology, 2008). This process is triggered by the acidic environment of the endosome, which induces a massive conformational change in the stem. Therapeutic agents targeting this region, such as the antibody CR8020, bind to the stem and lock it in its pre-fusion state, thereby preventing viral entry and infection (Throsby et al., PLOS ONE, 2008). Consequently, targeting the Group 2 HA stem offers a strategy to protect against a wide range of seasonal and potentially pandemic influenza strains.

Other names

Group 2 HA stalkInfluenza A virus haemagglutinin stalk region (Group 2)H3-like haemagglutinin stemHA2 subunit (stem portion)

The mechanism of action involves binding to the conserved stem region of the haemagglutinin (HA) protein, which prevents the pH-induced conformational change required for membrane fusion. By stabilizing the pre-fusion state of the HA trimer, these agents block the release of the viral genome into the host cell cytoplasm, effectively neutralizing the virus (Ekiert et al., Science, 2011; Corti et al., Science, 2011).