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Comparison of the impact of allelic polymorphisms in PfAMA1 on the induction of T Cell responses in high and low malaria endemic communities in Ghana

Show simple item record Ofori, E.A. Tetteh, J.K.A. Frimpong, A. Geneshan, H. Belmonte, M. Peters, B. Villasante, E. Sedegah, M. Ofori, M.F. Kusi, K.A. 2021-09-22T15:57:23Z 2021-09-22T15:57:23Z 2021
dc.description.abstract Background: Malaria eradication requires a combined efort involving all available control tools, and these eforts would be complemented by an efective vaccine. The antigen targets of immune responses may show polymor phisms that can undermine their recognition by immune efectors and hence render vaccines based on antigens from a single parasite variant inefective against other variants. This study compared the infuence of allelic polymor phisms in Plasmodium falciparum apical membrane antigen 1 (PfAMA1) peptide sequences from three strains of P. fal ciparum (3D7, 7G8 and FVO) on their function as immunodominant targets of T cell responses in high and low malaria transmission communities in Ghana. Methods: Peripheral blood mononuclear cells (PBMCs) from 10 subjects from a high transmission area (Obom) and 10 subjects from a low transmission area (Legon) were tested against 15 predicted CD8+T cell minimal epitopes within the PfAMA1 antigen of multiple parasite strains using IFN-γ ELISpot assay. The peptides were also tested in simi lar assays against CD8+enriched PBMC fractions from the same subjects in an efort to characterize the responding T cell subsets. Results: In assays using unfractionated PBMCs, two subjects from the high transmission area, Obom, responded pos itively to four (26.7%) of the 15 tested peptides. None of the Legon subject PBMCs yielded positive peptide responses using unfractionated PBMCs. In assays with CD8+enriched PBMCs, three subjects from Obom made positive recall responses to six (40%) of the 15 tested peptides, while only one subject from Legon made a positive recall response to a single peptide. Overall, 5 of the 20 study subjects who had positive peptide-specifc IFN-γ recall responses were from the high transmission area, Obom. Furthermore, while subjects from Obom responded to peptides in PfAMA1 from multiple parasite strains, one subject from Legon responded to a peptide from 3D7 strain only. Conclusions: The current data demonstrate the possibility of a real efect of PfAMA1 polymorphisms on the induc tion of T cell responses in malaria exposed subjects, and this efect may be more pronounced in communities with higher parasite exposure. en_US
dc.description.sponsorship This study was funded by the Bill and Melinda Gates Foundation under the Postdoctoral and Postgraduate Training in Infectious Diseases Research program, awarded to the Noguchi Memorial Institute for Medical Research (Global Health Grant number OPP52155: Koram). Ebenezer Addo Ofori was also supported by a graduate thesis research fund from a World Bank African Centres of Excellence grant (ACE02-WACCBIP: Awandare) en_US
dc.language.iso en en_US
dc.publisher Malaria Journal en_US
dc.subject Malaria en_US
dc.subject T-cells en_US
dc.subject IFN-γ ELISpot en_US
dc.subject Ghana en_US
dc.subject Apical membrane antigen 1 (PfAMA1) en_US
dc.title Comparison of the impact of allelic polymorphisms in PfAMA1 on the induction of T Cell responses in high and low malaria endemic communities in Ghana en_US
dc.type Article en_US

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