Hemagglutinin stem region (Influenza A and B viruses) (HA stem)

The hemagglutinin (HA) stem region is a highly conserved domain of the influenza virus surface glycoprotein, serving as a critical target for the development of universal influenza vaccines and broadly neutralizing antibodies (bnAbs) (Ekiert et al., 2009, Science; Corti et al., 2011, Science). While the HA head region frequently mutates via antigenic drift to evade the immune system, the stem region remains relatively invariant across diverse influenza A and B strains (Impagliazzo et al., 2015, Science). This region is essential for viral infectivity, as it undergoes a dramatic pH-triggered conformational change that facilitates the fusion of the viral envelope with the host cell's endosomal membrane (Bullough et al., 1994, Nature). Therapeutic agents targeting the HA stem, including monoclonal antibodies like CR9114 and small molecules like JNJ-63623872, typically function by binding to and stabilizing the pre-fusion state of the protein, effectively blocking the fusion process and preventing viral entry (Dreyfus et al., 2012, Science; van Dongen et al., 2019, Science). Consequently, the HA stem is a focal point for research aimed at providing broad-spectrum, long-lasting protection against both seasonal and pandemic influenza outbreaks (NIAID, 2023).

Other names

Hemagglutinin stalk regionHA stalkHA2 subunitConserved HA stem domainInfluenza hemagglutinin stem

Inhibition of pH-dependent membrane fusion by stabilizing the pre-fusion conformation of the hemagglutinin protein, thereby preventing the release of the viral genome into the host cytoplasm.