Influenza A virus hemagglutinin Group 1 stem region (HA Group 1 stem)

Hemagglutinin (HA) is the primary surface glycoprotein of the influenza virus, mediating both host cell attachment and membrane fusion [NIH, Wikipedia]. It is structurally divided into a highly variable globular head and a relatively conserved stem (or stalk) region [Frontiers in Immunology, Taylor & Francis]. The stem region of Group 1 influenza A viruses—encompassing subtypes such as H1, H2, H5, and H9—is a major focus for the development of universal influenza vaccines and broadly neutralizing antibodies (bnAbs) due to its low rate of antigenic drift [NIH, Science Translational Medicine]. Therapeutic agents targeting this region, such as the monoclonal antibody CR6261 or the small molecule JNJ-4796, primarily act by inhibiting the pH-triggered conformational changes necessary for viral-host membrane fusion [MDPI, European Biotechnology]. Additionally, some stem-binding antibodies can block the proteolytic maturation of the HA0 precursor or interfere with the egress of new viral particles from infected cells [Frontiers in Immunology, Oxford University Press]. Despite its promise, the stem region is considered immuno-recessive compared to the immunodominant head, posing a challenge for vaccine design [Science, PLOS One]. Current research aims to overcome this by using stabilized "headless" HA antigens or nanoparticle-based delivery systems to focus the immune response on these conserved epitopes [NIH, Science Translational Medicine].

Other names

Hemagglutinin stalk regionHA stem domainHA2 subunitGroup 1 HA stalkConserved HA stemHA fusion machinery

Inhibition of pH-dependent membrane fusion, inhibition of HA0 precursor cleavage, inhibition of viral egress, and induction of Fc-mediated effector functions such as antibody-dependent cellular cytotoxicity (ADCC) [NIH, Frontiers in Immunology].