Human immunodeficiency virus 1 envelope-specific B cell receptor (HIV-1 Env-specific BCR)

The Human immunodeficiency virus 1 envelope-specific B cell receptor (HIV-1 Env-specific BCR) is a membrane-bound immunoglobulin expressed on the surface of naïve or primed B cells that recognizes the HIV-1 envelope glycoprotein (Env) (Jardine et al., Science, 2013). These receptors are the primary targets for germline-targeting vaccine strategies, which aim to initiate the development of broadly neutralizing antibodies (bnAbs) capable of neutralizing diverse HIV-1 strains (Schief et al., Science, 2022). Because the precursors for these bnAbs are often rare in the human naïve B cell repertoire, specialized immunogens like eOD-GT8 60mer are designed to bind these specific BCRs with high affinity to trigger B cell activation and maturation (IAVI, 2021). In the context of HIV-1 infection, the natural evolution of these BCRs into bnAbs is often slow and inefficient, occurring in only a minority of infected individuals after years of exposure (Haynes et al., Nature Biotechnology, 2023). Therapeutic and prophylactic interventions focus on using engineered proteins or mRNA-encoded antigens to prime these BCRs and guide their evolution through sequential immunization (Moderna/IAVI, 2022). Successful targeting of these receptors is considered a critical step toward an effective HIV-1 vaccine.

Other names

HIV-1 envelope-specific BCRbnAb precursor B cell receptorGermline-encoded HIV-1 reactive BCRVRC01-class precursor BCRHIV-1 Env-reactive B-cell receptor

Germline-targeting immunogens bind specifically to rare naïve B cell receptors that have the potential to evolve into broadly neutralizing antibodies (bnAbs). This interaction triggers B cell activation, proliferation, and entry into germinal centers for somatic hypermutation and affinity maturation (Leggat et al., Science, 2022).