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Kibwana, Elizabeth K
(2025).
DOI: https://doi.org/10.21954/ou.ro.00102230
Abstract
Malaria remains a public health concern, and the development of a malaria vaccine remains a priority for reducing the global burden. A second-generation vaccine called R21 has recently been licensed by WHO for use in preventing malaria in children. It is a circumsporozoite protein-based particle vaccine with a higher proportion of CSP compared to the first recommended malaria vaccine RTS, S/AS01. I hypothesize that vaccination with R21/Matrix-M will induce improved CSP responses, leading to better controlled human malaria infection (CHMI) outcomes in semi-immune volunteers. The objective was to characterize immune responses to R21 and identify potential correlates of vaccine-induced protection in Kenyan adults using the CHMI model.
An extensive review provided an overview of CHMI research in Africa, focusing on vaccine efficacy and effects of naturally acquired immunity. I then worked on validating an existing qPCR assay for measuring parasite densities, as an outcome measure, following CHMI. Validation work showed that smaller extraction volumes <500μl, improved assay performance but larger volumes of 1000 μl decreased reproducibility.
I conducted several immunological assays to determine the quantity, quality, and durability of antibody responses. Here I demonstrated high, durable antibody titres to different epitopes indicating broad and diverse responses with complement fixing capabilities potentially enhancing neutralization ability against the parasite. Also, vaccination elicited a variety of antibody isotypes. Indicating a multifaceted immune response that could contribute to enhanced protection from infection.
Cellular responses investigation indicated sustained acquisition of memory B cells to both R21 protein and C-terminus. As well as an association between T follicular helper cells and memory B cells to R21 and a predominant Th2/Th17 population. Lastly, I observed that the route of challenge plays a major role in determining protective outcome following challenge.
The findings highlight comprehensive immunogenicity generated by R21/MM which is crucial in developing effective strategies against malaria.
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)
