Abstract:
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.
