HIV-1 envelope gp120 CD4 binding site-specific B-cell receptor (CH505 lineage) (CD4bs BCR (CH505))

The target consists of naïve and early-intermediate B-cell receptors (BCRs) that are precursors to broadly neutralizing antibodies (bNAbs) targeting the CD4 binding site (CD4bs) of the HIV-1 envelope glycoprotein gp120. These specific BCRs belong to the CH505 lineage, which was identified in an HIV-infected individual and shown to evolve broad neutralization over time (Saunders et al., 2019, Science). The target is defined by its ability to bind the CH505M5 outer-domain immunogen, a stabilized version of the gp120 outer domain designed to engage germline B cells. This immunogen is presented on the Pr-NP1 nanoparticle, a multivalent platform that enhances BCR signaling and B-cell activation through avidity effects (Haynes et al., 2023, Nature Reviews Immunology). In the context of HIV-1 infection, these BCRs represent the starting point for an immune response that can potentially overcome the virus's high mutational rate. By specifically targeting these precursors, researchers aim to guide the immune system through a defined pathway of affinity maturation to produce bNAbs. The interaction with the CH505M5-Pr-NP1 nanoparticle is intended to prime these rare B cells, making them the primary focus of subsequent booster immunizations (Bonsignori et al., 2016, Cell). This strategy addresses the challenge of HIV-1's structural diversity by focusing on highly conserved epitopes like the CD4bs.

Other names

CH505 lineage B-cell receptorsCD4bs-specific germline BCRsHIV-1 Env-specific B-cell receptorsCH505-specific B-cell precursorsNaïve and early-intermediate CH505 BCRs

Germline-targeting immunogen binding to naïve B-cell receptors to initiate affinity maturation of broadly neutralizing antibody precursors.