R21 AI151459-01A1

Duration

01/04/2020 - 31/03/2022

Coordinator

C Valim. University of Boston, USA

Funded by

National Institutes of Health_NIAID NIH-R21

Malaria continues to cause substantial childhood mortality in Africa, despite intensive control efforts. The development of an effective malaria vaccine is hindered by gaps in knowledge about both naturally acquired and vaccine-induced immunity. Current vaccine candidates generate antibodies against specific antigens, but the relationship between antibody functions and the level and duration of protection remains unclear. Subgroups of “hypo-responders” may also contribute to the moderate efficacy observed in clinical trials and may be individuals who struggle to mount effective natural immune responses.

Previous studies of naturally acquired antibody immunity have typically focused on quantifying antibody levels to individual proteins at a single time point, or infrequently (e.g. every six months or annually). However, as an individual’s immune profile is dynamic and shaped by repeated exposure to infection, such cross-sectional snapshots often fail to capture meaningful immune dynamics. Additionally, most studies have only measured antibody magnitude rather than the breadth and function of responses, with little data available on the longitudinal behaviour of key functional antibodies.

Our research leverages a unique dataset from a longitudinal cohort study in which children and adults were monitored monthly for two years. This detailed follow-up allows us to compare individuals who were frequently re-infected with those who remained free of infection or illness, and to analyse the durability and boosting of functional antibodies to merozoite and sporozoite antigens over time.

This study will be the first to longitudinally assess antibody isotypes, subclasses, and affinity to multiple antigens, alongside three key functional antibody activities—phagocytosis, cellular toxicity, and Fc-gamma receptor binding—measured monthly over a two-year period. By aligning subject-specific antibody breadth and functionality, we aim to identify the immune profiles associated with protection or susceptibility. These data will inform strategies to extend vaccine-induced protection, identify hypo-responders, and define correlates of protection that can serve as endpoints in future vaccine trials.

Ultimately, our findings will support the design of larger, prospective studies that are hypothesis-driven and better equipped to advance malaria vaccine development.

Total Funding

276.326 €