Promiscuous T-cell epitopes of Plasmodium merozoite surface protein 9 (PvMSP9) induces IFN-γ and IL-4 responses in individuals naturally exposed to malaria in the Brazilian Amazon

Abstract

Plasmodium vivax merozoite surface protein (PvMSP9) stimulates both cellular and humoral immune responses in individuals who are naturally infected by this parasite species. To identify immunodominant human T-cell epitopes in PvMSP9, we used the MHC class II binding peptide prediction algorithm ProPred. Eleven synthetic peptides representing predicted putative promiscuous T cell epitopes were tested in IFN-γ and IL-4 ELISPOT assays using peripheral blood mononuclear cells (PBMC) derived from 142 individuals from Rondonia State, Brazil who had been naturally exposed to P. vivax infections. To determine whether the predicted epitopes are preferentially recognized in the context of multiple alleles, MHC Class II typing of the cohort was also performed. Five synthetic peptides elicited robust cellular responses, and the overall frequencies of IFN-γ and IL-4 responders to at least one of the promiscuous peptides were 62% and 46%, respectively. The frequencies of IFN-γ and IL-4 responders to each peptide were not associated with a particular HLA-DRB1 allelic group since most of the peptides induced a response in individuals of 12 out of 13 studied allelic groups. The prediction of promiscuous epitopes using ProPred led to the identification of immunodominant epitopes recognized by PBMC from a significant proportion of a genetically heterogeneous population exposed to malaria

The evolution and diversity of a low complexity vaccine candidate, merozoite surface protein 9 (MSP-9), in Plasmodium vivax and closely related species

“…The actual motifs of this LCR accumulate more synonymous than non-synonymous substitutions indicating some functional constrain. On the other hand, the N-terminal region of Pv MSP-9 induced IFN-γ and IL-4 cytokine responses, confirming the presence of T-cell epitopes in this region of the protein (Lima-Junior et al, 2010). The presence of these T cell epitopes (Lima-Junior et al, 2010) indicates that the response induced by the LCRs could be low grade and non-neutralizing (Schofield 1991).…”

“…On the other hand, the N-terminal region of Pv MSP-9 induced IFN-γ and IL-4 cytokine responses, confirming the presence of T-cell epitopes in this region of the protein (Lima-Junior et al, 2010). The presence of these T cell epitopes (Lima-Junior et al, 2010) indicates that the response induced by the LCRs could be low grade and non-neutralizing (Schofield 1991). Overall, there is an elicited immune response which association with protection in P. falciparum and/or P. vivax remains to be determined.…”

“…The role of Pf MSP-9 in the erythrocyte invasion, the fact that there are orthologs in several Plasmodium species, and that it is immunogenic as shown in animal models as well as in natural exposed individuals, made MSP-9 a protein of interest for vaccine development (Sharma et al, 1998; Pimtanothai et al, 2000; Kushwaha et al, 2001; Oliveira-Ferreira et al, 2004; Lima-Junior et al, 2010; Lima-Junior et al, 2012). Hence, it is important to further explore its genetic diversity and how such polymorphism is being altered or maintained in Plasmodium .…”

B cell epitope mapping and characterization of naturally acquired antibodies to the Plasmodium vivax Merozoite Surface Protein-3α (PvMSP-3α) in malaria exposed individuals from Brazilian Amazon

“…Information at the amino acid level about the epitopes of proteins recognized by antibodies is important for their use as biological tools, therapeutic molecules, and for understanding molecular recognition events in general [64]. In this context, T and B cell epitope prediction programs are largely used in malaria research [65–66]. However, the use of chemically prepared arrays of short peptides has emerged as a powerful tool to identify and characterize epitopes recognized by antibodies [35–36].…”

Using Population Genetics to Guide Malaria Vaccine Design

“…Additional antigens identified as potential P.vivax vaccine candidates include PvMSP3, PvMSP4, PvMSP5 and PvRBPs I and II [38]. PvMSP9 has also been revealed as a promising vaccine candidate in recent studies [189].…”