PI24/00049

Duration

01/01/2025 - 31/12/2027

Coordinator

Carlota Dobaño

Funded by

Instituto de Salud Carlos III

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 WHO strategic goals for a world free of malaria, there is a strong need of highly efficacious vaccines. Although the RTS,S/AS01 vaccine was approved for use in African children and has recently started to be implemented, it demonstrated a modest efficacy during the phase 3 clinical trial.

Hence, a better understanding of the determinants of long-lasting immunity induced by the RTS,S is urgent to support next-generation vaccines aiming to provide the maximum coverage to target populations and a significant global impact. Our previous data demonstrated that high antibody levels and avidity are associated with RTS,S vaccine efficacy. However, the antigen-specific B cell and T follicular helper (Tfh) cells supporting such potent antibody responses have not been fully deciphered.

To fill these knowledge gaps, this project aims to develop an in-depth immunoprofiling and analysis of clonal evolution and TCR specificity of the Tfh compartment of young African children participating in the largest multicenter RTS,S phase 3 clinical trial ever performed, with systematic clinical data collection and samples already available.

By combining immunophenotyping of B and Tlymphocyte populations, TCR sequencing and functional characterisation of the protective antibodies after primary and booster immunisation, and the impact of baseline responses, we will elucidate hallmarks of long-lasting antibody responses and vaccine efficacy.

This work represents a unique opportunity to understand the immune correlates of protection and further define antigènic epitopes by studying a strictly defined population, and paving the way to future translational research involving isolation of monoclonal antibodies for public health interventions.

Total Funding

177.500€