Influenza A virus hemagglutinin stem (HA stem) (HA stem)

The Influenza A virus hemagglutinin (HA) stem is a highly conserved region of the virus's primary surface glycoprotein, serving as a critical component of the viral entry machinery (Nature, 2009, 458(7238):597-601). While the globular head of the HA protein undergoes frequent antigenic drift, the stem region—comprised of the HA2 subunit and the proximal portion of HA1—remains largely unchanged across diverse influenza subtypes (Science, 2011, 333(6044):850-856). This conservation makes the HA stem a primary target for "universal" influenza vaccines and broadly neutralizing monoclonal antibodies (bnAbs) that aim to provide protection against multiple seasonal and pandemic strains (Frontiers in Immunology, 2018, 9:2645). Mechanistically, the stem mediates the fusion of the viral envelope with the host endosomal membrane through a pH-triggered conformational change (Journal of Virology, 2013, 87(17):9742-9754). Therapeutic agents, such as the monoclonal antibodies CR6261 and MEDI8852, bind to this epitope to stabilize the pre-fusion structure, thereby preventing the release of the viral genome into the host cytoplasm (Cell, 2016, 166(3):596-608). Despite its potential, the HA stem is characterized by low immunodominance, presenting a challenge for vaccine design that requires specialized strategies to redirect the immune response away from the head (NPJ Vaccines, 2019, 4:17).

Other names

Hemagglutinin stalkHA stalkHA2 subunitConserved HA stem regionHemagglutinin stem epitope

Binding to the conserved stem region to inhibit the pH-induced conformational change required for viral-host membrane fusion, thereby blocking viral entry (Nature, 2009; Science, 2011).