Vaccine Research Center 01-class germline B cell receptor (VRC01-class gBCR) (VRC01-class gBCR)

Vaccine Research Center 01-class (VRC01-class) germline B cell receptors (BCRs) are the unmutated precursors to a potent family of broadly neutralizing antibodies (bNAbs) that target the conserved CD4 binding site (CD4bs) of the HIV-1 envelope glycoprotein (Env) (Zhou et al., Science, 2010). These receptors are structurally defined by their use of the IGHV1-2 germline gene and specific constraints, such as a five-amino-acid light-chain complementarity-determining region 3 (CDRL3), which are necessary to avoid steric clashes with the viral glycan shield (Wu et al., Science, 2011). In modern HIV vaccine design, these BCRs are the primary targets for germline-targeting immunogens, such as eOD-GT8 60mer, which are engineered to bind these rare naive B cells with high affinity (Jardine et al., Science, 2013). The goal of targeting these receptors is to trigger the initial step of a multi-stage vaccination strategy that guides the immune system through a specific evolutionary pathway of somatic hypermutation (Leggat et al., Science, 2022). Successfully activating these germline BCRs is considered a critical milestone in developing a vaccine capable of eliciting protective immunity against the diverse global strains of HIV-1 (IAVI, 2021).

Other names

IGHV1-2*02 germline B cell receptorVRC01-precursor B cell receptorCD4-binding site germline B cell receptorVRC01-class naive B cell receptor

Germline-targeting immunogens act as agonists that bind to and activate specific naive B cells expressing VRC01-class germline receptors, initiating somatic hypermutation and affinity maturation toward a broadly neutralizing phenotype (Schief et al., Science, 2013).