B-cell receptor specific for HIV-1 envelope glycoprotein (BCR-HIV-Env) (BCR-HIV-Env)

B-cell receptors (BCRs) specific for HIV-1 envelope (Env) epitopes are the primary targets in germline-targeting vaccine strategies, which aim to induce broadly neutralizing antibodies (bNAbs) (Schief et al., 2015, Science). These receptors include both unmutated germline precursors (uBCRs) found on naive B cells and mature BCRs that have undergone somatic hypermutation (Jardine et al., 2013, Science). The biological function of these receptors is to recognize conserved epitopes on the HIV-1 Env protein, such as the CD4 binding site, and initiate B-cell activation and differentiation (Zhou et al., 2010, Science). In the context of HIV-1 infection, these BCRs are critical for the eventual development of broad immunity, although this process is typically slow and rare in natural infection. Therapeutic immunogens, such as eOD-GT8 60mer, are designed to bind specifically to these germline BCRs to prime the immune system and guide the maturation process toward bNAb production (Leggat et al., 2022, Science). This approach represents a shift in vaccinology, focusing on the precise manipulation of B-cell ontogeny to overcome the structural challenges posed by the HIV-1 envelope (Kulp et al., 2016, Science).

Other names

HIV-1 Env-specific B-cell receptorGermline B-cell receptorMature B-cell receptorBroadly neutralizing antibody precursoruBCRVRC01-class precursor

Targeted activation of specific germline B-cell precursors by engineered immunogens to initiate a directed affinity maturation pathway toward broadly neutralizing antibody production.