B-cell receptor specific for HIV-1 envelope glycoprotein gp120 (anti-gp120 BCR)

The B-cell receptor (BCR) specific for the HIV-1 envelope glycoprotein gp120 is a primary target for modern HIV vaccine design, particularly in germline-targeting strategies [Jardine et al., 2013, Science]. These receptors are membrane-bound immunoglobulins on the surface of B cells that recognize specific epitopes on the gp120 subunit, such as the CD4 binding site (CD4bs) or the V3 loop [Burton and Hangartner, 2016, Annu Rev Immunol]. In the context of HIV infection or vaccination, these BCRs are engaged by viral antigens or synthetic immunogens to initiate B-cell activation, clonal expansion, and somatic hypermutation [Schief et al., 2021, Science]. The ultimate goal of targeting these receptors is to elicit the production of secreted anti-gp120 antibodies, especially broadly neutralizing antibodies (bNAbs) that can protect against a wide range of HIV-1 variants [Haynes et al., 2012, NEJM]. Pre-existing anti-gp120 antibodies in the serum can also influence the immune response by masking epitopes or forming immune complexes that modulate further BCR engagement [Bonsignori et al., 2017, Sci Transl Med]. Understanding the interaction between immunogens and these specific BCRs is essential for developing vaccines that can overcome the high mutational escape of HIV-1. This target is central to the reverse vaccinology approach, where the desired antibody is used to design the immunogen that will trigger the corresponding BCR.

Other names

gp120-reactive B-cell receptorHIV-1 envelope-specific BCRanti-gp120 antibodiesVRC01-class germline B-cell receptorB-cell receptor / pre-existing or vaccine-induced anti-gp120 antibodies

Vaccine-induced activation of specific B-cell lineages through B-cell receptor engagement to elicit neutralizing antibodies against the HIV-1 gp120 protein.