Human B-cell receptor recognizing HIV-1 envelope germline-targeting epitope (HIV-1 Env germline-targeting BCR)

Human B-cell receptors (BCRs) recognizing HIV-1 envelope (Env) germline-targeting epitopes are the primary targets of a novel vaccine strategy designed to elicit broadly neutralizing antibodies (bnAbs). These receptors are found on rare naive B cells that possess specific genetic features, such as the VH1-2*02 gene segment in the case of VRC01-class antibodies, which allow them to potentially evolve into potent neutralizers of diverse HIV-1 strains [1, 4]. Because native HIV-1 Env glycoproteins typically do not bind these germline-reverted receptors, researchers use structure-based design to create 'germline-targeting' immunogens, such as eOD-GT8, that can specifically engage and activate these precursor B cells [3, 10]. Once activated, these B cells migrate to germinal centers where they undergo rounds of somatic hypermutation and affinity maturation, guided by sequential boosting with different immunogens [2, 13]. This process is intended to 'shepherd' the B-cell lineage toward the development of high-affinity bnAbs that can overcome the extreme genetic diversity of HIV-1 [7, 18]. Successful priming of these receptors has been demonstrated in human clinical trials (e.g., IAVI G001), marking a significant milestone in rational vaccine design for infectious diseases [1, 11].

Other names

Broadly neutralizing antibody precursor B-cell receptorbnAb precursor BCRVRC01-class B-cell receptorNaive B-cell receptor for HIV-1 EnvGermline-reverted B-cell receptor10E8-class precursor BCRBG18-class precursor BCR

Activation of rare naive B-cell precursors through specific binding of engineered immunogens to initiate affinity maturation and somatic hypermutation toward broadly neutralizing antibodies.