B-cell receptor specific for Norovirus genogroup I genotype 1 and genogroup II genotype 4 VP1 epitopes (GI.1/GII.4 VP1-specific BCR)

The B-cell receptor (BCR) specific for Norovirus VP1 epitopes is the fundamental mediator of the adaptive immune response against Norovirus, the leading cause of acute viral gastroenteritis (Atmar et al., 2011, NEJM). These receptors recognize the major capsid protein, VP1, which consists of a conserved shell (S) domain and a variable protruding (P) domain. The P2 subdomain within the P domain is of particular clinical importance as it contains the binding sites for host histo-blood group antigens (HBGAs) and the primary neutralizing epitopes for the GI.1 and GII.4 genogroups (Lindesmith et al., 2011, PLOS Pathogens). Vaccines such as HIL-214 utilize virus-like particles (VLPs) to target these BCRs, inducing the production of antibodies that block the virus from binding to its cellular receptors (Parra et al., 2017, CSH Perspect Med). A significant challenge in targeting these receptors is the rapid antigenic drift of GII.4 strains, which necessitates the development of vaccines that can stimulate BCRs recognizing conserved, broadly neutralizing epitopes (Debbink et al., 2012, J Virol). Understanding the specificity and breadth of these BCRs is essential for creating effective, long-lasting immunotherapies and vaccines against diverse norovirus strains. Monoclonal antibodies derived from these BCRs are also being explored as potential therapeutic agents for immunocompromised patients. The interaction between the BCR and the VP1 epitope determines the potency and breadth of the resulting antibody response. Monitoring the frequency and specificity of these BCRs serves as a key biomarker for vaccine efficacy in clinical trials. Overall, these receptors are the primary target for inducing protective immunity against the most prevalent norovirus genotypes.

Other names

Norovirus VP1-specific B-cell receptorAnti-norovirus VP1 BCRNorwalk virus-specific B-cell receptorGI.1/GII.4 specific BCR

Activation of B-cell receptors by viral antigens or vaccine virus-like particles (VLPs) triggers B-cell differentiation into antibody-secreting plasma cells and memory B cells, resulting in the production of neutralizing antibodies that block viral attachment to host cell receptors.