Abstract
Protein α-helical coiled coil structures that elicit antibody responses, which block critical functions of medically important microorganisms, represent a means for vaccine development. By using bioinformatics algorithms, a total of 50 antigens with α-helical coiled coil motifs orthologous to Plasmodium falciparum were identified in the P. vivax genome. The peptides identified in silico were chemically synthesized; circular dichroism studies indicated partial or high α-helical content. Antigenicity was evaluated using human sera samples from malaria-endemic areas of Colombia and Papua New Guinea. Eight of these fragments were selected and used to assess immunogenicity in BALB/c mice. ELISA assays indicated strong reactivity of serum samples from individuals residing in malaria-endemic regions and sera of immunized mice, with the α-helical coiled coil structures. In addition, ex vivo production of IFN-γ by murine mononuclear cells confirmed the immunogenicity of these structures and the presence of T-cell epitopes in the peptide sequences. Moreover, sera of mice immunized with four of the eight antigens recognized native proteins on blood-stage P. vivax parasites, and antigenic cross-reactivity with three of the peptides was observed when reacted with both the P. falciparum orthologous fragments and whole parasites. Results here point to the α-helical coiled coil peptides as possible P. vivax malaria vaccine candidates as were observed for P. falciparum. Fragments selected here warrant further study in humans and non-human primate models to assess their protective efficacy as single components or assembled as hybrid linear epitopes.
Highlights
Despite the important reduction in reported malaria incidence during the last decade in a number of countries worldwide, malaria infection still represents one of the major global public health threats
P. vivax genome bioinformatic analysis A total of 50 P. vivax fragments, 25–57 residues long and containing the a-helical coiled coil motifs, were selected based on proteome and transcriptome data of P. falciparum orthologues present in erythrocytic parasite stages (Tables 1 and S1)
Variable homology (29 to 100% identity) was observed between P. falciparum and the corresponding P. vivax fragments (Table S1), most of which (32 antigens) were greater than 60% homologous
Summary
Despite the important reduction in reported malaria incidence during the last decade in a number of countries worldwide, malaria infection still represents one of the major global public health threats. The World Health Organization (WHO) estimated an annual global burden of 207 million malaria cases and 627,000 deaths in 2012 [1]. Of at least six different malaria parasite species which can be transmitted to humans, Plasmodium vivax is the second most parasite species of epidemiological importance with 70–80 million cases estimated per year worldwide [2]. Significant progress has been achieved with P. falciparum where several vaccine candidates are currently in clinical development [6]; with one being considered for licensure [7]. Development of P. vivax vaccines has been significantly neglected and only a few candidates have been selected for clinical testing [8]
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