Polymorphism and epitope sharing between the alleles of merozoite surface protein-1 of Plasmodium falciparum among Indian isolates

Abstract

Background: The C-terminal region of merozoite surface protein-1 (MSP-1) is one of the leading candidates for vaccination against the erythrocytic stages of malaria. However, a major concern in the development of MSP-1 based malaria vaccine is the polymorphism observed in different geographical Plasmodium falciparum isolates. To explore whether the sequence heterogeneity of PfMSP-1 leads to variation in naturally acquired anti-MSP-1₁₉ antibodies, the present study was undertaken to study PfMSP-1₁₉ sequence polymorphism in malaria-endemic villages in eastern India and also carried out a competition enzyme-linked immunosorbent assay using three PfMSP-1₁₉ variant forms. Methods: The sequence variations in the C-terminal region of PfMSP-1₁₉ were determined in a malaria endemic region. Three PfMSP-1₁₉ variants were produced in Escherichia coli (PfMSP1₁₉QKNG-L, PfMSP1₁₉EKNG-L and PfMSP1₁₉ETSR-F) and an immunodepletion assay was carried out using the corresponding patients' sera. Results: Results revealed predominance of PfMAD20 allele among Indian field isolates. Seven PfMSP-1₁₉ variant forms were isolated in a singe geographical location. Three of PfMSP-1₁₉ variant forms when expressed in E. coli showed presence of cross-reaction as well as variant specific antibodies in malaria infected patient sera. Conclusion: The present study demonstrates the existence of allele specific antibodies in P. falciparum-infected patient sera, however their role in protection requires further investigation. These results thereby, suggest the importance of a multi-allelic PfMSP-1₁₉ based vaccine for an effective malaria control.