Human B-cell receptor recognizing HIV-1 group M envelope epitopes (HIV-1 Env-specific BCR)

Human B-cell receptors (BCRs) recognizing HIV-1 group M envelope (Env) epitopes are the primary targets for modern "germline-targeting" vaccine strategies (Schief et al., 2022). These receptors are membrane-bound immunoglobulins on the surface of B cells that specifically bind to conserved regions of the HIV-1 Env protein, such as the CD4 binding site, the V3-glycan supersite, or the membrane-proximal external region (MPER) (Burton & Hangartner, 2016). In the context of HIV-1, the goal of therapeutic intervention is to stimulate these specific BCRs to undergo somatic hypermutation and affinity maturation, eventually leading to the production of broadly neutralizing antibodies (bNAbs) (Haynes et al., 2023). These bNAbs are capable of neutralizing a wide range of HIV-1 strains by blocking viral entry into host cells. Because the precursor B cells for these bNAbs are often rare in the human repertoire, specialized immunogens like eOD-GT8 are designed to bind these BCRs with high affinity to initiate the immune response (Jardine et al., 2013). Understanding the structural and genetic characteristics of these BCRs is crucial for developing an effective HIV-1 vaccine that can overcome the virus's high mutation rate and glycan shielding. Successful engagement of these receptors is a key milestone in immunogen design and is currently being evaluated in several clinical trials (Stamatatos et al., 2021).

Other names

HIV-1 envelope-specific B-cell receptorAnti-HIV-1 Env BCRGermline B-cell receptor for HIV-1 EnvHIV-1 group M Env-reactive BCRbNAb-precursor B-cell receptor

Vaccine-mediated engagement and activation of specific germline B-cell receptors to induce somatic hypermutation and the development of broadly neutralizing antibodies (bNAbs) (Schief et al., 2022).