VRC01-class B-cell receptor (VRC01-class BCR) (VRC01-class BCR)

VRC01-class B-cell receptors (BCRs) are a specific class of immunoglobulin receptors on B cells that serve as the precursors for broadly neutralizing antibodies (bNAbs) targeting the CD4-binding site (CD4bs) of the HIV-1 envelope glycoprotein (Env) (Zhou et al., 2010, Science). These receptors are defined by specific genetic and structural features, most notably the use of the IGHV1-2 germline gene and a short light-chain complementarity-determining region 3 (LCDR3) (Jardine et al., 2013, Science). This structural configuration allows the BCR to mimic the host CD4 receptor's interaction with the virus, a critical step for neutralizing diverse HIV strains. In modern vaccinology, VRC01-class BCRs are the primary focus of germline-targeting strategies, where engineered immunogens like eOD-GT8 60mer are designed to bind and activate these rare B-cell precursors (Leggat et al., 2022, Science). The therapeutic objective is to initiate a specific lineage of B-cell maturation that, through successive vaccinations, leads to the production of high-affinity bNAbs. This approach addresses the challenge of HIV's extreme diversity by focusing the immune response on highly conserved functional sites of the viral spike. Monitoring the frequency and maturation of these BCRs in clinical trials serves as a key indicator of vaccine efficacy (Dosenovic et al., 2015, Cell). Ultimately, targeting these receptors represents a paradigm shift in vaccine design, moving from empirical methods to precision molecular targeting of the immune repertoire.

Other names

VRC01-like B-cell receptorIGHV1-2-derived B-cell receptorCD4-binding site-directed B-cell receptor

Germline-targeting immunogens bind to and activate specific germline B-cell receptors to initiate the development of broadly neutralizing antibodies through somatic hypermutation.