Non-variant specific antibody responses to the C-terminal region of merozoite surface protein-1 of Plasmodium falciparum (PfMSP-1(19)) in Iranians exposed to unstable malaria transmission

BACKGROUND: The C-terminal region of Plasmodium falciparum merozoite surface protein-1 (PfMSP-1(19)) is a leading malaria vaccine candidate antigen. However, the existence of different variants of this antigen can limit efficacy of the vaccine development based on this protein. Therefore, in this study, the main objective was to define the frequency of PfMSP-1(19 )haplotypes in malaria hypoendemic region of Iran and also to analyse cross-reactive and/or variant-specific antibody responses to four PfMSP-1(19 )variant forms. METHODS: The PfMSP-1(19 )was genotyped in 50 infected subjects with P. falciparum collected during 2006-2008. Four GST-PfMSP-1(19 )variants (E/TSR/L, E/TSG/L, E/KNG/F and Q/KNG/L) were produced in Escherichia coli and naturally occurring IgG antibody to these proteins was evaluated in malaria patients' sera (n = 50) using ELISA. To determine the cross-reactivity of antibodies against each PfMSP-1(19 )variant in P. falciparum-infected human sera, an antibody depletion assay was performed in eleven corresponding patients' sera. RESULTS: Sequence data of the PfMSP-1(19 )revealed five variant forms in which the haplotypes Q/KNG/L and Q/KNG/F were predominant types and the second most frequent haplotype was E/KNG/F. In addition, the prevalence of IgG antibodies to all four PfMSP-1(19 )variant forms was equal and high (84%) among the studied patients' sera. Immunodepletion results showed that in Iranian malaria patients, Q/KNG/L variant could induce not only cross-reactive antibody responses to other PfMSP-1(19 )variants, but also could induce some specific antibodies that are not able to recognize the E/TSG/L or E/TSR/L variant forms. CONCLUSION: The present findings demonstrated the presence of non-variant specific antibodies to PfMSP-1(19 )in Iranian falciparum malaria patients. This data suggests that polymorphism in PfMSP-1(19 )is less important and one variant of this antigen, particularly Q/KNG/L, may be sufficient to be included in PfMSP-1(19)-based vaccine.