Akshay Tiwari

Biophysical model explains the diversity of antibody responses to multivalent antigens

Designing vaccines that generate potent antibody responses is often a challenge, especially against rapidly evolving pathogens like HIV. In recent studies, the use of vaccines carrying ‘multivalent’ antigen have shown promise in eliciting broadly reactive antibody responses.
These antibody responses are mounted by B cells after getting primed in germinal centres—priming involves antigen presentation, intracellular signaling, followed by antigen extraction. Thus, B cells with high affinity to the antigen are preferentially selected and consequently dominate the responses. While antigens of low valency trigger the selection of high-affinity B cells, emerging evidences suggest that antigens of high valency elicit diverse B cell responses. The mechanisms underlying the dependence of the diversity of responses on antigen valency however remain poorly understood.
We have developed a biophysical model of B cell selection in germinal centres, accounting for the presentation and extraction of multivalent antigen. This model revealed that high valency antigens allow low-affinity B cells to receive signal and extract the antigens at levels comparable to those observed in high-affinity B cells. This finding opens up new avenues for research and potentially informs the development of more effective vaccines and immunotherapeutics.