Background: Plasmodium 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.
Results: Three 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.
Conclusion: The 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.
Keywords: Antigenic diversity; Immune evasion; Low complexity regions; Vaccine design.