PI25/00363

Duration

2026-2029

Coordinator

Luis Manuel Molinos Albert

Funded by

Instituto de Salud Carlos III

Malaria is the most important parasitic disease and one of the leading causes of death among African children. Among the World Health Organization’s strategic goals to achieve a malaria-free world is the need for highly effective vaccines.

Understanding durable humoral immunity against malaria

Although the RTS,S/AS01 vaccine (RTS,S) was approved for use in African children, its efficacy in phase III clinical trials was modest. For this reason, there is an urgent need to improve our understanding of the correlates of efficient and long-lasting immunity, in order to guide the development of next-generation vaccines and provide optimal coverage to target populations, with a significant global impact.

Our previous data have shown that high antibody levels and high antibody avidity are associated with vaccine efficacy. However, the molecular and functional features that underpin strong humoral immune responses have not yet been fully elucidated.

Study design and methodological approach

To address these knowledge gaps, this project aims to carry out an in-depth evaluation of the humoral immune response in children who participated in the multicentre phase III clinical trial of the RTS,S vaccine, using previously collected samples.

By combining high-throughput techniques for B-cell isolation, monoclonal antibody cloning, immunophenotyping and functional characterisation, we will elucidate the distinctive signature of efficient and durable humoral immunity.

Implications for vaccine development and immunotherapy

This work represents a unique opportunity to understand correlates of protection and vaccine efficacy through the study of a well-defined population, supported by systematic clinical data collection and the availability of samples from the largest clinical trial conducted to date in African children.

From a translational perspective, our findings may be applied to the improvement of vaccine candidates and to the development of monoclonal antibody-based immunotherapies for passive immunisation.

Total funding

183.500 €

Funded by the Instituto de Salud Carlos III