| dc.description.abstract |
It is widely accepted that the C-terminal 42 kDa (p42) and 19 kDa (p19) processing fragments of plasmodium Merozoite Surface Protein-1 (MSP-1) are targets of immune protection. To begin to assess the degree of polymorphism in these MSP-1 vaccine candidates, we have investigated the sequence diversity in the p.vivax MSP-1 p42 processing fragment, in 19 natural isolates, from p.vivax infected patients in Kataragama. Sequence analysis of PvMSP-1 p42 in the 19 PCR positive isolates reveald 11 sequences of Belem origin and 8 sequences of Salvador-1 (Sal-1) origin. Among the isolates, these two stains are 98-100% homologous across this region, with one notable exception. This corresponds to a highly polymorphic block of 38 amino acids (24% amino acid homology among isolates). However, this polymorphism appears to be derived largely by re-assorting a dimorphism at each variable position. This type of restricte variability suggests that in spite of its diversity, there may nevertheless be a defined structure for this region of the molecule and that the diversity may be functionally important. Alternatively, it may be specifically designed for maximal effect in immune evasion, as a highly exposed immunogenic loop structure. In striking contrast, a single nucleotide substitution was detected in the cysteine rich C-terminal 19 kDa region, resulting in a lysine to glutamate substitution. This was detected in only one isolate among the 19 isolates investigated for sequence diversity. Since the PvMSP-1 C-terminal antigen is clearly hypervariable in the context of natural infections, a vaccine based on a single version of this antigen, might not induce an effective immunity against the multiple forms. In contrast, the PvMSP-1 p19 domain appears to be well conserved and thus appears to be a considerably more promising vaccine candidate. |
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