Immunopeptidomics reveals conserved malaria CD8+ T-cell antigens across species and life stages
Researchers identified 453 HLA-I-bound peptides from Plasmodium-infected reticulocytes, including conserved antigens that elicited CD8+ T-cell responses in humans, non-human primates and rodents, suggesting new vaccine targets.
An immunopeptidomics analysis of reticulocytes infected with Plasmodium vivax uncovered 453 unique HLA-class I peptides derived from 166 parasite proteins. Among these, 75 antigens were housekeeping proteins expressed throughout multiple stages of the parasite life cycle and showed high conservation between P. vivax and P. falciparum. The same peptide sequences were presented by a range of HLA-A, HLA-B, HLA-C and the non-classical HLA-E alleles in different donors.
The immunogenicity of the newly identified epitopes was confirmed using blood samples from individuals infected with either P. vivax or P. falciparum. CD8+ T-cell responses to several of the antigens were also detected in the liver and blood of non-human primates following natural infection or immunization with attenuated parasites. In rodent models, two of the antigens conferred protective CD8+ T-cell-mediated immunity.
These findings indicate that the conserved, cross-stage antigens could serve as components of a malaria vaccine capable of targeting multiple Plasmodium species.
"Identical peptides were presented in different individuals by the same or distinct HLA-A, HLA-B and HLA-C alleles, as well as by the non-classical HLA-E allele," the study authors reported.
"T cell responses to several of these antigens were observed in the blood and liver of non-human primates after infection with Plasmodium or immunization with attenuated parasites," the authors added.
