Non-variant specific antibody responses to the C-terminal region of merozoite surface protein-1 of Plasmodium falciparum (PfMSP-119) in Iranians exposed to unstable malaria transmission

Abstract

BackgroundThe C-terminal region of Plasmodium falciparum merozoite surface protein-1 (PfMSP-119) 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-119 haplotypes in malaria hypoendemic region of Iran and also to analyse cross-reactive and/or variant-specific antibody responses to four PfMSP-119 variant forms.MethodsThe PfMSP-119 was genotyped in 50 infected subjects with P. falciparum collected during 2006-2008. Four GST-PfMSP-119 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-119 variant in P. falciparum-infected human sera, an antibody depletion assay was performed in eleven corresponding patients' sera.ResultsSequence data of the PfMSP-119 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-119 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-119 variants, but also could induce some specific antibodies that are not able to recognize the E/TSG/L or E/TSR/L variant forms.ConclusionThe present findings demonstrated the presence of non-variant specific antibodies to PfMSP-119 in Iranian falciparum malaria patients. This data suggests that polymorphism in PfMSP-119 is less important and one variant of this antigen, particularly Q/KNG/L, may be sufficient to be included in PfMSP-119-based vaccine.