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

Publikation: Bidrag til tidsskriftTidsskriftartikel

  • Nora Céspedes
  • Catherine Habel
  • Lopez-Perez, Mary
  • Angélica Castellanos
  • Andrey V. Kajava
  • Catherine Servis
  • Ingrid Felger
  • Remy Moret
  • Myriam Arévalo-Herrera
  • Giampietro Corradin
  • Sócrates Herrera

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.

OriginalsprogEngelsk
Artikelnummere100440
TidsskriftPLoS ONE
Vol/bind9
Udgave nummer6
ISSN1932-6203
DOI
StatusUdgivet - 24 jun. 2014
Eksternt udgivetJa

ID: 174276266