Malaria is one of the major infectious diseases that causes high disease burden worldwide. According to World malaria Report 2024, 263 million cases and 597,000 deaths are related to malaria in 2023. Most of the disease incidences are observed in low- and middle-income countries (LMICs) in sub-Saharan Africa, South America and Southeast Asia. Importantly, the deaths related to malaria disease are observed mainly in children. In the last two decades, two malaria vaccines have been approved by WHO and implemented in several countries in Africa. Even with low protective efficacy, the vaccines is making major differences in the vaccinees. Howeve, the disease is not eradicated and vaccine-induced protective efficacy wanes, highlighting the need to develop highly efficacious malaria vaccines.
In this project, I proposed to perform an in-depth immunological analysis of B cell response to malaria, making use of the unique clinical trial samples from controlled human malaria infection studies. To that end, I characterized cellular and humoral immunity against two distinct genetically attenuated parasite exposures in malaria-naive individuals. This thorough analysis revealed a broad convergence between the two arms of adaptive immunity to the parasites. Furthermore, this study also uncovered malaria antigens targeted by the antibody response, that are unique to late- but not early-liver stage arresting parasites. Additionally, from the samples, I isolated B cells and characterized the evolution of their response over repeated parasite exposure.
Collectively, this work advanced our understanding on different components of adaptive immunity that contribute to protection against malaria and thereby help develop efficacious vaccines.
