BG18-class V3 glycan broadly neutralizing antibody precursor B cell receptor (BG18-class BCR)

BG18-class V3 glycan broadly neutralizing antibody (bnAb) precursor B cell receptors (BCRs) are the specific naive B cell populations targeted by germline-targeting HIV-1 vaccines (Steichen et al., 2019; Science). These BCRs possess unique genetic features, such as long heavy-chain complementarity-determining region 3 (HCDR3) loops (typically ≥20 amino acids) and specific D-gene usage, which allow them to recognize the conserved N332-glycan supersite on the HIV-1 envelope (Env) protein (Barnes et al., 2018; Nat Struct Mol Biol). Because these precursors are exceptionally rare in the human naive B cell repertoire (estimated at approximately 1 in 50 million), specialized immunogens like N332-GT5 have been engineered to bind them with high affinity and initiate their expansion (Kalyuzhniy et al., 2024; Sci Immunol). Once activated, these B cells are guided through a sequential immunization regimen to undergo somatic hypermutation and affinity maturation, eventually producing mature BG18-class antibodies capable of neutralizing a broad range of HIV-1 strains (Steichen et al., 2024; Science). This strategy represents a sophisticated approach to overcoming the challenges of HIV-1 diversity and the low immunogenicity of conserved neutralizing epitopes (Schief et al., 2023; IAVI).

Other names

BG18-like precursor B cell receptorV3-glycan-targeting broadly neutralizing antibody precursorN332-glycan-targeting B cell receptorBG18-class precursor BCRV3-glycan bnAb precursor

Germline-targeting (GT) priming involves the use of engineered immunogens to activate rare naive B cells with specific BCR features that can evolve into broadly neutralizing antibodies (bnAbs). For BG18-class precursors, the immunogen N332-GT5 binds to the BCR and initiates germinal center responses, followed by sequential boosting with increasingly native-like trimers to drive somatic hypermutation and affinity maturation (Steichen et al., 2019; Science; Kalyuzhniy et al., 2024; Sci Immunol).