Impact of Allelic Polymorphisms in Pfama1 on the Induction of T-Cell Responses in Malaria Endemic Communities in Ghana

Show simple item record Ofori, E.A. 2020-10-09T15:57:43Z 2020-10-09T15:57:43Z 2019-07
dc.description MPhil. Molecular Cell Biology of Infectious Diseases en_US
dc.description.abstract The eradication of malaria requires a combined effort involving all available control tools, and these efforts would be complemented by an effective vaccine. An effective malaria vaccine should be capable of inducing protective immune responses against variant forms of the parasite and in a genetically diverse population. Allelic polymorphisms in antigens that are targets of protective immune responses are a major drawback to vaccine development. This study investigated the influence of allelic polymorphisms in Apical Membrane Antigen 1 (AMA1) peptide sequences from three strains of P. falciparum (3D7, 7G8 and FVO) on their function as targets of immunodominant T cell responses. PBMCs were obtained from subjects from Legon (low malaria transmission zone) and Obom (high malaria transmission zone) and tested against 15 synthetic PfAMA1 peptides using ELISpot assay. The peptides were also tested for induction of CD4+ and CD8+ specific T cell IFN-γ responses by ELISpot using PBMCs with depleted T cell subsets. The 15 peptides represent six sets of allelic peptides from the three parasite strains. Data was expressed as the spot forming cells (sfc) per million PBMCS and analysed at two levels; first for positivity for immunodominance based on a set of criteria, and second for statistical differences between sfc/million PBMC data between peptides with any allelic set. None of the unfractionated PBMCs of subjects from Legon made positive response to any of the peptide tested. However, 2 subjects from Obom responded positively to 4 out of the 15 peptides used. Two of the 4 peptides were alleles and belong to the same allelic set (7G8 vs 3D7/FVO respectively) while the remaining two peptides belong to different allelic sets. In assays with CD8+ enriched PBMCs, a single subject from Legon and 3 subjects from Obom made positive response to 4 new peptides in addition to 2 peptides that made positive responses from the unfractionated PBMCs. In similar assays with CD4+ cells, there were no positive responses to any peptide for subjects from Legon. However, subject s made a positive response to 2 peptides belonging to the same allelic set. Overall, majority of the peptides which made either positive response by the set criteria or statistically significant responses had amino acid variability at positions 1 and 4 and most of the substitutions were to a charged amino residue. Also, majority of the specific IFN-γ response were from subjects belonging to the high malaria transmission zone. On the basis of this data, polymorphisms in PfAMA1 affect the induction of T- cell responses in malaria exposed subjects, and this effect is more pronounced in areas with high parasite exposure. en_US
dc.language.iso en en_US
dc.publisher University of Ghana en_US
dc.subject Allelic Polymorphisms en_US
dc.subject Pfama1 en_US
dc.subject T-Cell en_US
dc.subject Malaria en_US
dc.subject Ghana en_US
dc.title Impact of Allelic Polymorphisms in Pfama1 on the Induction of T-Cell Responses in Malaria Endemic Communities in Ghana en_US
dc.type Thesis en_US

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