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PLoS One. 2014 Jun 24;9(6):e100440. doi: 10.1371/journal.pone.0100440. eCollection 2014.

Plasmodium vivax antigen discovery based on alpha-helical coiled coil protein motif.

Author information

1
Malaria Vaccine and Drug Development Center (MVDC), Cali, Colombia; School of Health, University of Valle, Cali, Colombia.
2
Biochemistry Department, University of Lausanne, Epalinges, Switzerland.
3
Caucaseco Scientific Research Center, Cali, Colombia.
4
Malaria Vaccine and Drug Development Center (MVDC), Cali, Colombia; Fundación Centro de Primates, Cali, Colombia.
5
Centre de Recherches de Biochimie Macromoleculaire (CRBM) and Institut de Biologie Computationnelle (IBC), CNRS, University of Montpellier, Montpellier, France; University ITMO, St. Petersburg, Russia.
6
Swiss Tropical and Public Health Institute, Basel, Switzerland.
7
Hôpital Saint Camille, Ouagadougou, Burkina Faso.
8
Malaria Vaccine and Drug Development Center (MVDC), Cali, Colombia; Caucaseco Scientific Research Center, Cali, Colombia.

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.

PMID:
24959747
PMCID:
PMC4069070
DOI:
10.1371/journal.pone.0100440
[Indexed for MEDLINE]
Free PMC Article

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