Identifying molecular features of potent antibody and memory B-cell responses associated with RTS,S malaria vaccine efficacy

Malaria is the most important parasitic disease being a leading cause of death among young children, particularly in sub-Saharan Africa.

In the context of the World Health Organization (WHO) strategic goals for a world free of malaria, there is a strong need of highly efficacious vaccines.

Despite the RTS,S/AS01 (RTS) vaccine candidate was recently approved for use in African children, it demonstrated a modest efficacy during phase 3 clinical trials.

Hence, a better understanding of the determinants of long-lasting immunity induced by the RTS,S is required to support improved next-generation vaccines aiming to provide the maximum coverage to target populations.

In this regard, previous serological analyses demonstrated that high antibody levels and avidity are associated with vaccine efficacy in African children recipients.

However, the molecular mechanisms and the cellular immune phenotypes supporting such potent antibody responses have not been fully deciphered.

To fill these knowledge gaps, we propose to develop an in-depth humoral immunoprofiling within the large multicenter RTS,S phase 3 clinical trial, using already collected samples from African children participants.

By generating a collection of antigen-specific monoclonal antibodies, I will investigate the molecular features of the RTS,S-induced memory B-cell response and the most relevant target epitopes.

In parallel, I will identify the lymphocyte populations mobilized upon highly responding serological profiles, to subsequently develop a multivariable analysis integrating clinical-epidemiological, serological and cellular datasets to elucidate hallmarks of potent antibody responses and vaccine efficacy.