VRC01-class broadly neutralizing antibody precursor B cell receptor (VRC01-class BCR precursor)

VRC01-class broadly neutralizing antibody (bnAb) precursor B cell receptors (BCRs) are the germline-encoded receptors on naive B cells that serve as the starting point for the development of VRC01-class antibodies, which target the CD4 binding site (CD4bs) of the HIV-1 envelope (Env) protein (Zhou et al., 2010, Science). These precursors are characterized by their use of the IGHV1-2*02 germline gene and a short (5-amino acid) light chain complementarity-determining region 3 (LCDR3) (Jardine et al., 2016, Science). In the context of HIV-1 vaccine development, these BCRs are considered critical therapeutic targets for germline-targeting immunogens, such as eOD-GT8 60mer, which are designed to overcome the low affinity of natural Env for naive B cells (Jardine et al., 2013, Science). The activation of these specific precursors is the first step in a multi-stage vaccination strategy aimed at inducing somatic hypermutation and affinity maturation toward broad neutralization (Leggat et al., 2022, Science). Successful engagement of these targets has been demonstrated in human clinical trials (IAVI G001), where the eOD-GT8 60mer immunogen induced the expansion of VRC01-class precursor B cells in 97% of vaccinees (Cohen, 2022, Science).

Other names

VRC01-class germline B cell receptorIGHV1-2*02-encoded B cell receptorCD4-binding site antibody precursorVRC01-class naive B cell receptor

Germline-targeting immunogens bind specifically to the VRC01-class precursor B cell receptors on naive B cells, initiating their activation and expansion to begin the process of somatic hypermutation toward mature broadly neutralizing antibodies (Jardine et al., 2013, Science; Leggat et al., 2022, Science).