B-cell receptor recognizing HIV-1 envelope epitopes (BCR)

B-cell receptors (BCRs) recognizing HIV-1 envelope (Env) epitopes are the primary targets for next-generation HIV-1 vaccine strategies, particularly those employing germline targeting (Jardine et al., Science 2013). These receptors exist in two main states: the germline or unmutated common ancestor (UCA) forms found on naive B cells, and the mature forms that have undergone somatic hypermutation to achieve high affinity and broad neutralization (Wu et al., Science 2010). The goal of targeting these receptors is to initiate the development of broadly neutralizing antibodies (bnAbs) by binding to specific germline BCRs and guiding their maturation through sequential immunization (Haynes et al., Nature Biotechnology 2023). This process aims to overcome the high diversity of HIV-1 by focusing the immune response on conserved epitopes such as the CD4 binding site or the V3-glycan supersite (Sok & Burton, Nature Reviews Immunology 2018). In clinical trials, engineered immunogens like eOD-GT8 60mer have successfully activated these specific germline B-cell precursors in humans (Leggat et al., Science 2022). Understanding the structural and genetic characteristics of these BCRs is crucial for designing vaccines that can reliably elicit protective immunity against HIV-1 (IAVI, 2023).

Other names

HIV-1 Env-specific B-cell receptorGermline-encoded B-cell receptorMature B-cell receptorbnAb precursor BCRVRC01-class B-cell receptorUnmutated common ancestor (UCA) BCR

Germline-targeting immunogens bind to specific naive B-cell receptors to initiate the development of broadly neutralizing antibody lineages through directed affinity maturation (Leggat et al., Science 2022).