Abstract
BackgroundPlasmodium vivax merozoite surface protein 3α (PvMSP3α) is a promising vaccine candidate which has shown strong association with immunogenicity and protectiveness. Its use is however complicated by evolutionary plasticity features which enhance immune evasion. Low complexity regions (LCRs) provide plasticity in surface proteins of Plasmodium species, but its implication in vaccine design remain unexplored. Here population genetic, comparative phylogenetic and structural biology analysis was performed on the gene encoding PvMSP3α.ResultsThree LCRs were found in PvMSP3α block II. Both the predicted tertiary structure of the protein and the phylogenetic trees based on this region were influenced by the presence of the LCRs. The LCRs were mainly B cell epitopes within or adjacent. In addition a repeat motif mimicking one of the B cell epitopes was found within the PvMSP3a block II low complexity region. This particular B cell epitope also featured rampant alanine substitutions which might impair antibody binding.ConclusionThe findings indicate that PvMSP3α block II possesses LCRs which might confer a strong phenotypic plasticity. The phenomenon of phenotypic plasticity and implication of LCRs in malaria immunology in general and vaccine candidate genes in particular merits further exploration.
Highlights
Plasmodium vivax merozoite surface protein 3α (PvMSP3α) is a promising vaccine candidate which has shown strong association with immunogenicity and protectiveness
Given that high diversity was observed in malaria and in P. vivax, it was important to identify the relevant polymorphisms that contribute to antigenic escape and its potential to develop a “vaccine resistant strain” [1]
PvMSP3α gene subtypes and clonality of infection Of the 50 dried blood spot (DBS) samples that were confirmed for P.vivax infection, the MSP3α gene was successfully amplified in 48 of the 50 samples
Summary
Plasmodium vivax merozoite surface protein 3α (PvMSP3α) is a promising vaccine candidate which has shown strong association with immunogenicity and protectiveness. Low complexity regions (LCRs) provide plasticity in surface proteins of Plasmodium species, but its implication in vaccine design remain unexplored. Population genetic studies can guide vaccine design by (2019) 19:6 species,this is perhaps most curious since LCRs are associated with host pathogen interaction and phenotypic plasticity, enhancing their role in evading the immune system [6, 7]. This is in addition to the fact that LCRs are highly frequent in Plasmodium parasite antigens. Extensive recombination has been largely been ascribed as the major reason behind the failure to link specific alleles to geographical regions [17,18,19]
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