Abstract:
Background
Sterile protection against malaria, most likely mediated by parasite-specific CD8+ T cells,
has been achieved by attenuated sporozoite vaccination of animals as well as malarianaïve
and malaria-exposed subjects. The circumsporozoite protein (CSP)-based vaccine,
RTS,S, shows low efficacy partly due to limited CD8+ T cell induction, and inclusion of such
epitopes could improve RTS,S. This study assessed 8-10mer CSP peptide epitopes, present
in predicted or previously positive P. falciparum 3D7 CSP 15mer overlapping peptide
pools, for their ability to induce CD8+ T cell IFN-γ responses in natural malaria-exposed
subjects.
Methods
Cryopreserved PBMCs from nine HLA-typed subjects were stimulated with 23 8-10mer
CSP peptides from the 3D7 parasite in IFN-γ ELISpot assays. The CD8+ T cell specificity of
IFN-γ responses was confirmed in ELISpot assays using CD8+ T cell-enriched PBMC fractions
after CD4+ cell depletion.
Results
Ten of 23 peptide epitopes elicited responses in whole PBMCs from five of the nine subjects.
Four peptides tested positive in CD8+ T cell-enriched PBMCs from two previously
positive responders and one new subject. All four immunodominant peptides are restricted
by globally common HLA supertypes (A02, A03, B07) and mapped to regions of the CSP antigen with limited or no reported polymorphism. Association of these peptide-specific
responses with anti-malarial protection remains to be confirmed.
Conclusions
The relatively conserved nature of the four identified epitopes and their binding to globally
common HLA supertypes makes them good candidates for inclusion in potential multi-epitope
malaria vaccines