Research Articles
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A research article reports the results of original research, assesses its contribution to the body of knowledge in a given area, and is published in a peer-reviewed scholarly journal. The faculty publications through published and on-going articles/researches are captured in this community
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Item 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(Springer Nature, 2021) Ofori, E.A.; Tetteh, J.K.A.; Frimpong, A.; Ganeshan, H.; Belmonte, M.; Peters, B.; Villasante, E.; Sedegah, M.; Ofori, M.F.; . Kusi, K.A.Background: Malaria eradication requires a combined effort involving all available control tools, and these efforts would be complemented by an effective vaccine. The antigen targets of immune responses may show polymorphisms that can undermine their recognition by immune effectors and hence render vaccines based on antigens from a single parasite variant ineffective against other variants. This study compared the influence of allelic polymorphisms in Plasmodium falciparum apical membrane antigen 1 (PfAMA1) peptide sequences from three strains of P. falciparum (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 similar assays against CD8 + enriched PBMC fractions from the same subjects in an effort to characterize the responding T cell subsets. Results: In assays using unfractionated PBMCs, two subjects from the high transmission area, Obom, responded positively 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-specific 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 effect of PfAMA1 polymorphisms on the induction of T cell responses in malaria exposed subjects, and this effect may be more pronounced in communities with higher parasite exposure.Item 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(Malaria Journal, 2021) 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.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.Item Characterization of T cell activation and regulation in children with asymptomatic Plasmodium falciparum infection(Malaria Journal, 2018-07) Frimpong, A.; Kusi, K.A.; Tornyigah, B.; Ofori, M.F.; Ndifon, W.Background Asymptomatic Plasmodium infections are characterized by the absence of clinical disease and the ability to restrict parasite replication. Increasing levels of regulatory T cells (Tregs) in Plasmodium falciparum infections have been associated with the risk of developing clinical disease, suggesting that individuals with asymptomatic infections may have reduced Treg frequency. However, the relationship between Tregs, cellular activation and parasite control in asymptomatic malaria remains unclear. Methods In a cross-sectional study, the levels of Tregs and other T cell activation phenotypes were compared using flow cytometry in symptomatic, asymptomatic and uninfected children before and after stimulation with infected red blood cell lysates (iRBCs). In addition, the association between these T cell phenotypes and parasitaemia were investigated. Results In children with asymptomatic infections, levels of Tregs and activated T cells were comparable to those in healthy controls but significantly lower than those in symptomatic children. After iRBC stimulation, levels of Tregs remained lower for asymptomatic versus symptomatic children. In contrast, levels of activated T cells were higher for asymptomatic children. Strikingly, the pre-stimulation levels of two T cell activation phenotypes (CD8+CD69+ and CD8+CD25+CD69+) and the post-stimulation levels of two regulatory phenotypes (CD4+CD25+Foxp3+ and CD8+CD25+Foxp3+) were significantly positively correlated with and explained 68% of the individual variation in parasitaemia. A machine-learning model based on levels of these four phenotypes accurately distinguished between asymptomatic and symptomatic children (sensitivity = 86%, specificity = 94%), suggesting that these phenotypes govern the observed variation in disease status. Conclusion Compared to symptomatic P. falciparum infections, in children asymptomatic infections are characterized by lower levels of Tregs and activated T cells, which are associated with lower parasitaemia. The results indicate that T cell regulatory and activation phenotypes govern both parasitaemia and disease status in paediatric malaria in the studied sub-Saharan African population.Item Novel Strategies for Malaria Vaccine Design(Frontiers in Immunology, 2018-11) Frimpong, A.; Kusi, K.A.; Ofori, M.F.; Ndifon, W.The quest for a licensed effective vaccine against malaria remains a global priority. Even though classical vaccine design strategies have been successful for some viral and bacterial pathogens, little success has been achieved for Plasmodium falciparum, which causes the deadliest form of malaria due to its diversity and ability to evade host immune responses. Nevertheless, recent advances in vaccinology through high throughput discovery of immune correlates of protection, lymphocyte repertoire sequencing and structural design of immunogens, provide a comprehensive approach to identifying and designing a highly efficacious vaccine for malaria. In this review, we discuss novel vaccine approaches that can be employed in malaria vaccine design.