Influenza A hemagglutinin stem region (HA stem)

The Influenza A hemagglutinin (HA) stem region is a highly conserved domain of the HA glycoprotein, which is the primary surface protein of the influenza virus (NIH, 2024). Unlike the globular head of HA, which undergoes rapid antigenic drift, the stem region remains relatively stable across various subtypes, including Group 1 (e.g., H1, H5) and Group 2 (e.g., H3, H7) (MDPI, 2020; NIH, 2020). This conservation makes it an ideal target for universal influenza vaccines and broadly neutralizing antibodies (bnAbs) (NIH, 2020; ResearchGate, 2024). The stem region plays a critical role in the viral life cycle by mediating the fusion of the viral envelope with the host cell endosomal membrane through a pH-triggered conformational change (NIH, 2020; Semanticscholar, 2016). Therapeutic agents targeting this region, such as the monoclonal antibodies VIR-2482 and MEDI8852, work by stabilizing the pre-fusion state of HA, thereby preventing the release of the viral genome into the host cell (ResearchGate, 2024). Clinical development of these agents aims to provide broad protection against both seasonal and pandemic influenza strains (ResearchGate, 2024).

Other names

Hemagglutinin stalk regionHA stalkHA2 subunitConserved stem epitopeFusogenic region of hemagglutinin

Inhibition of pH-dependent conformational changes in the hemagglutinin stem to block viral-host membrane fusion and prevent viral entry.