B-cell receptor (BCR) recognizing HIV-1 Envelope (Env) epitopes (BCR-HIV-Env)

The B-cell receptor (BCR) recognizing HIV-1 Envelope (Env) epitopes is a primary target for next-generation HIV-1 vaccine design, specifically those aiming to induce broadly neutralizing antibodies (bNAbs) (Schief et al., 2015, Science). These receptors are membrane-bound immunoglobulins that recognize conserved regions of the HIV-1 Env trimer, such as the CD4 binding site (CD4bs), the V3-glycan patch, or the membrane-proximal external region (MPER) (Burton & Hangartner, 2016, Annu Rev Immunol). In HIV-1 infection, most BCRs target variable or non-neutralizing epitopes, but a small subset can evolve into bNAbs capable of neutralizing diverse viral strains (Kwong & Mascola, 2018, Immunity). Therapeutic strategies like "germline-targeting" involve using engineered immunogens, such as eOD-GT8 60mer, to specifically bind and activate naive B cells expressing BCRs with the genetic potential to become bNAbs (Jardine et al., 2016, Science). This interaction triggers B-cell activation and initiates the affinity maturation process required to achieve the high levels of somatic hypermutation seen in mature bNAbs (Dosenovic et al., 2015, Cell). Monitoring these BCRs through high-throughput sequencing is a key biomarker for evaluating vaccine efficacy in clinical trials (IAVI, 2021). Challenges include the rarity of these precursor B cells in the human repertoire and the immunodominance of distracting, non-protective epitopes (Stamatatos et al., 2021, Science). Successful engagement of these BCRs is considered the first step in a multi-stage vaccination protocol to elicit protective immunity against HIV-1.

Other names

HIV-1 Env-specific B-cell receptorAnti-HIV BCRbNAb-precursor B-cell receptorHIV-1 Envelope-specific BCRVRC01-class BCR

Activation of germline B-cell receptors to initiate the development and affinity maturation of broadly neutralizing antibodies (bNAbs) against conserved HIV-1 Envelope epitopes (Jardine et al., 2013, Science).