title: Human T-cell recognition of synthetic peptides representing conserved and variant sequences from the merozoite surface protein 2 of Plasmodium falciparum.
abstract: Merozoite surface protein 2 (MSP2) is a malaria vaccine candidate currently undergoing clinical trials. We analyzed the peripheral blood mononuclear cell (PBMC) response to synthetic peptides corresponding to conserved and variant regions of the FCQ-27 allelic form of MSP2 in Ghanaian individuals from an area of hyperendemic malaria transmission and in Danes without exposure to malaria. PBMC from 20-39% of Ghanaians responded to each of the peptides by proliferation and 29-36% had PBMC which produced interferon-gamma (IFN-gamma) in response to peptide stimulation. In Danes, there was no proliferation to two of the peptides and only PBMC from 5% of the individuals proliferated to the other three peptides. IFN-gamma production was not detected to any peptide. In both Danes and Ghanaians in only a few instances was IL-4 detected in the PBMC cultures. Overall PBMC from 79% of the Ghanaians responded by proliferation and/or cytokine secretion to at least one of three peptides tested, whereas responses were only observed in 14% of Danes (P = 0.002). These data suggest that the Ghanaians had expanded peripheral blood T-cell populations recognizing the peptides as a result of natural infection. The findings are encouraging for the development of a vaccine based on these T-epitope containing regions of MSP2, as the peptides were broadly recognized suggesting that they can bind to diverse HLA alleles and also because they include conserved MSP2 sequences. Immunisation with a vaccine construct incorporating the sequences present in these peptides could thus be expected to be immunogenic in a high percentage of individuals and lead to the establishment of memory T-cells, which can be boosted through natural infection.
authors.affiliation: Centre for Medical Parasitology, University of Copenhagen, Denmark. parasite@biobase.dk
authors.forename: T G
authors.initials: TG
authors.lastname: Theander
authors.forename: L
authors.initials: L
authors.lastname: Hviid
authors.forename: D
authors.initials: D
authors.lastname: Dodoo
authors.forename: E A
authors.initials: EA
authors.lastname: Afari
authors.forename: J B
authors.initials: JB
authors.lastname: Jensen
authors.forename: C M
authors.initials: CM
authors.lastname: Rzepczyk
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan; D017124:Conserved Sequence; D003718:Denmark; D014644:Genetic Variation; D005869:Ghana; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D008213:Lymphocyte Activation; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D010446:Peptide Fragments; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium; D015847:Interleukin-4; D007371:Interferon-gamma