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HEIndividual fellowship2024–2025

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

Horizon Europe — Marie Skłodowska-Curie Actions

Duration
2024-01-01 → 2025-12-31
EU contribution
€165,313
Participants
1
Scheme
HORIZON-TMA-MSCA-PF-EF

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Results in brief

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

Malaria is a major global health concern, jeopardizing the future of childhood, equity and economic development of endemic countries, particularly in the African continent. Hence, the progress towards an effective vaccine is a global priority to protect vulnerable populations and achieve elimination goals. Although RTS,S/AS01 (RTS,S) is the first malaria vaccine approved for use in African children, its efficacy during phase 3 clinical trials was partial and its duration modest. Understanding the factors behind limited vaccine efficacy and identifying the determinants of protective immunity is required to support improved next-generation vaccines aiming to provide maximum coverage. We previously reported that high antibody levels to the circumsporozoite (CSP) RTS,S immunogen are associated with vaccine efficacy. However, the molecular features supporting optimal or suboptimal antibody responses have not been fully deciphered in pediatric populations. To fill these knowledge gaps, this project envisions to perform an in-depth humoral immunoprofiling of RTS,S vaccine-induced responses in African young children. By combining high-throughput technologies including methods to directly clone and characterize large antibody collections from single antigen-specific B cells, immunophenotyping of lymphocyte populations and functional and biophysical characterization, we will elucidate the hallmarks of potent long-lasting antibody responses, and identify the mechanisms compromising them. The main goal is to generate basic scientific knowledge by studying a vulnerable group previously unexplored, to aid future development of vaccines and immunotherapeutics, and improve human health using next-generation antibody science.

Data: CORDIS, © European Union

Project objective

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.

Original text from CORDIS.

Participants

  • FUNDACION PRIVADA INSTITUTO DE SALUD GLOBAL BARCELONA · BarcelonaCoordinatorSpain

Links

Data: CORDIS, © European Union