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
Loading...
Date
2021
Journal Title
Journal ISSN
Volume Title
Publisher
Malaria Journal
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.
Description
Keywords
Malaria, T-cells, IFN-γ ELISpot, Ghana, Apical membrane antigen 1 (PfAMA1)