Influenza A hemagglutinin stem epitope (HA stem epitope)

The Influenza A hemagglutinin (HA) stem epitope is a highly conserved region located on the stalk of the HA protein, the primary surface glycoprotein of the influenza virus (Nature, 2022). While the globular head of HA undergoes frequent antigenic drift, the stem region remains relatively stable across diverse influenza subtypes, making it a critical target for universal vaccine design (PNAS, 2022). Antibody 31.a.83 is a broadly neutralizing human antibody that targets a "supersite of vulnerability" within this stem, specifically involving the conserved helix A (Cell, 2016). Binding of 31.a.83 to this epitope prevents the pH-triggered conformational changes required for the fusion of the viral envelope with the host endosomal membrane, thereby neutralizing the virus (J. Virol, 2019). This epitope is accessible in both Group 1 and Group 2 influenza A viruses, allowing antibodies like 31.a.83 to provide heterosubtypic protection (Science, 2018). Therapeutic targeting of this site aims to overcome the limitations of current strain-specific vaccines by eliciting or providing antibodies that can neutralize a wide range of seasonal and potential pandemic strains (Frontiers in Immunology, 2020). Research into this target often involves chimeric hemagglutinins (cHAs) designed to focus the immune response away from the immunodominant head and toward the conserved stem (PNAS, 2022).

Other names

HA stemHA stalkCentral stem epitopeHemagglutinin stem supersiteHelix A epitopeHA stem supersite of vulnerability

Neutralization of viral infection by binding to the conserved stem region of hemagglutinin, thereby preventing the pH-induced conformational changes required for membrane fusion between the viral envelope and the host endosomal membrane.