Last Updated: 02/12/2024
A novel strategy for understanding the functional impact of variation in Plasmodium falciparum merozoite vaccine candidates
Objectives
To study the impact of variation in two merozoite antigens and assess their temporal allele frequency and naturally acquired immune response distribution over 20 years in the Kilifi population.
Plasmodium falciparum merozoite proteins are required for the invasion of erythrocytes, an essential step for parasite survival and malaria pathogenesis. These proteins are also targets of naturally acquired immunity, making them potential vaccine targets. However, vaccine trials have shown the host often generates allele-specific responses which are not protective against heterologous non-vaccine alleles. This problem has been attributed to the polymorphisms in these antigens, but the actual functional impact of polymorphism has not been systematically studied. To achieve the objective the study will use antibodies targeting the conserved and polymorphic regions of each antigen to determine the functional impact of polymorphisms on erythrocyte recognition and invasion in vitro. Finally, a recently developed transfection strategy will be used to develop a novel barcoded parallel phenotyping assay. This assay will mimic natural infections, which often contain multiple parasite variants invading erythrocytes in the presence of antibodies, allowing to determine whether variation has an impact on immune evasion. This research will provide a set of assays to study other merozoite antigens in the future.
Jan 2016 — Dec 2021
$926,863
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