Naive B-cell receptors of V3-glycan broadly neutralizing antibody lineages

Naive B-cell receptors (BCRs) of V3-glycan broadly neutralizing antibody (bNAb) lineages are the specific germline-encoded receptors on precursor B cells that have the potential to develop into antibodies targeting the V3-glycan supersite of the HIV-1 envelope (Env) protein [Steichen et al., 2016]. These receptors are the primary focus of "germline-targeting" vaccine strategies, which aim to overcome the low affinity of native HIV-1 Env for naive B cells [Sok et al., 2016]. The V3-glycan supersite, centered around the N332 glycan, is a major target for potent bNAbs like PGT121, 10-1074, and DH270 [Saunders et al., 2019]. By using engineered immunogens designed to bind these specific naive BCRs, researchers hope to initiate the complex process of somatic hypermutation required to achieve broad neutralization [Bonsignori et al., 2017]. This target is critical for the development of a preventative HIV-1 vaccine, as it represents the starting point for the induction of protective antibody responses [Dosenovic et al., 2015]. Successful engagement of these BCRs is the first step in a multi-stage vaccination protocol designed to guide the immune system toward producing antibodies that can neutralize a wide range of HIV-1 variants [Escolano et al., 2016].

Other names

Germline V3-glycan bNAb precursorsV3-glycan-targeting naive B-cell receptorsN332-glycan bNAb precursorsV3-glycan bNAb germline-encoded receptors

Germline-targeting immunogens bind to and activate specific naive B-cell receptors to initiate somatic hypermutation and affinity maturation toward broadly neutralizing antibody phenotypes.