Immunodominant T cell peptides from four candidate malarial antigens as biomarkers of protective immunity against malaria
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Date
2023
Journal Title
Journal ISSN
Volume Title
Publisher
Vaccine
Abstract
A malaria vaccine with high efficacy and capable of inducing sterile immunity against malaria within
genetically diverse populations is urgently needed to complement ongoing disease control and elimination efforts. Parasite-specific IFN-c and granzyme B-secreting CD8 + T cells have been identified as key
mediators of protection and the rapid identification of malaria antigen targets that elicit these responses
will fast-track the development of simpler, cost-effective interventions. This study extends our previous
work which used peripheral blood mononuclear cells (PBMCs) from adults with life-long exposure to
malaria parasites to identify immunodominant antigen-specific peptide pools composed of overlapping
15mer sequences spanning full length proteins of four malarial antigens. Our current study aimed to
identify CD8 + T cell epitopes within these previously identified positive peptide pools. Cryopreserved
PBMCs from 109 HLA-typed subjects were stimulated with predicted 9-11mer CD8 + T cell epitopes from
P. falciparum circumsporozoite protein (CSP), apical membrane antigen 1 (AMA1), thrombospondin
related anonymous protein (TRAP) and cell traversal for ookinetes and sporozoites (CelTOS) in
FluoroSpot assays. A total of 135 epitopes out of 297 tested peptides from the four antigens were experimentally identified as positive for IFN-c and/or granzyme B production in 65 of the 109 subjects. Forty three of 135 epitopes (32 %) were promiscuous for HLA binding, with 31 of these promiscuous epitopes
(72 %) being presented by HLA alleles that fall within at least two different HLA supertypes. Furthermore,
about 52 % of identified epitopes were conserved when the respective sequences were aligned with those
from 16 highly diverse P. falciparum parasite strains. In summary, we have identified a number of conserved epitopes, immune responses to which could be effective against multiple P. falciparum parasite
strains in genetically diverse populations.
Description
Research Article
Keywords
FluoroSpot, Malaria, Granzyme B, T cells, Epitope