Discovering targets of long-lived humoral immunity for Strep A vaccine design.

Enduring antibody-mediated immunity is critical for vaccines to provide protection from infectious disease. Despite the success of vaccines to date, there are still numerous pathogens that require a vaccination solution, including Group A Streptococcus. Most vaccines work by inducing antibodies, however the majority of the antibody response is short-lived and does not provide long-lasting protection. Selecting key antigens that can elicit long-term protective immunity across human populations continues to be a major roadblock for vaccine development. Long-lived and affinity matured humoral immunity is generated within germinal centres, which are transient structures that form within lymphoid tissues and in which B cells undergo mutation of their immunoglobulin genes and receive essential selection and survival signals from T follicular helper cells. Therefore, the antigens recognised by cells from the germinal centre are promising candidates to be targeted in the induction of long-lived immunity through vaccination. This project will use cutting-edge and innovative approaches to discover the Strep A antigens targeted by T follicular helper cells and memory B cells. It will involve studying human responses to GAS in blood samples from healthy individuals in an infectious challenge model, in human tonsil tissue and organoids and involve techniques including flow cytometry, single-cell sequencing, bioinformatics, molecular biology, protein purification, lentiviral transduction, and high throughput screening.