Characterization of the MSP-1 Protein in Field Samples of Plasmodium falciparum and its Homology to the Plasmodium vivax MSP-1 Protein

Abstract

About 300 to 500 million people are diagnosed with malaria annually and about a million deaths occur mostly in children and pregnant women. Despite enormous effort and resources towards malaria control, problems of resistance by the parasite and mosquito have only made a bad situation worse. Hence, the search for alternate modes of treatment like vaccine development using merozoite surface protein-1 (MSP-1) is being explored. This protein is a 185-200 kDa precursor molecule that undergoes two proteolytic steps to form a C-terminal 19-kDa fragment (MSP-119) that remains on the surface of the merozoite and is used for attachment and invasion of red blood cells as PfMSP-119 in Plasmodium falciparum and PvMSP119 in Plasmodium vivax. Studies using humans and nonhuman primates have shown that antibodies against the PfMSP-119 protein prevent merozoites from attachment and invasion of red blood cells. Such studies involving the PvMSP-119 protein have been limited because of inability to maintain the Plasmodium vivax parasite in a continuous in-vitro culture. Meanwhile, both PfMSP-119 and PvMSP- 119 have been found to be located in block 17 that is highly conserved and dimorphic. PfMSP-119 in nature exist as two basic allelic forms identified as Pfk1/Welcome (Q-KNG) and PfMAD20 (E-TSR); with exception to this dimorphism resulting from few nonsynonymous single nucleotide polymorphisms (SNPs) at position 1644, 1691, 1700 and 1701 that produce allelic forms like: E-KNG, E-TSR, Q-KNG and Q-TSR. PvMSP-119 in nature also exists as two basic forms identified as Belem and Sal-I strains. This study was designed to evaluate the possibility that in addition to meiotic recombination, different allelic forms of PfMSP-119 may also form as a result of mutational or gene conversion activities. Since protective immunity is species-specific, elucidation of the extent of homology of PfMSP-119 to PvMSP-119 as possible vaccine candidates in a multi-subunit vaccine was attempted.