RESTRICTED T-CELL EPITOPE DIVERSITY IN THE CIRCUMSPOROZOITE PROTEIN FROM PLASMODIUM FALCIPARUM POPULATIONS PREVALENT IN IRAN

Parasite genotyping studies have indicated that the Plasmodium falciparum populations circulating in Iran are genetically diverse and that multiple genotype infections are observed regularly. We wished to extend the analysis to the Pfcsp gene, coding for the dominant sporozoite surface antigen on which the leading malaria vaccine candidate RTS,S is based. Infected blood samples were collected mainly from Iranian, as well as Afghani and Pakistani, patients on admission with falciparum malaria. DNA was purified from 90 isolates, and from these, 21 fragments corresponding to Pfcsp and 69 fragments corresponding to the 3'-end conserved domain were amplified and sequenced. Overall diversity was low. Six patterns were noted for the repeat region, but mixed genotypes were not observed in any of the isolates. T cell epitopes also displayed limited diversity, with only five haplotypes (combined Th2R/Th3R epitopes) noted, and of these, three were dominant, accounting for 94% of the 90 sequences. These observations are akin to those observed in Thai P. falciparum isolates, where a particular Pfscp Th2R/Th3R haplotype seems to be maintained in an otherwise genetically diverse parasite population. The data imply that the selective pressure that maintains a restricted T cell epitope is caused by factors outside the mammalian host immune responses. Furthermore, they sustain the notion that protective responses induced by RTS,S vaccination are not strain-specific.