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

• Published in: PloS one 2014-06, Vol.9 (6), p.e100440-e100440
• Main Authors: Céspedes, Nora, Habel, Catherine, Lopez-Perez, Mary, Castellanos, Angélica, Kajava, Andrey V, Servis, Catherine, Felger, Ingrid, Moret, Remy, Arévalo-Herrera, Myriam, Corradin, Giampietro, Herrera, Sócrates
• Format: Article
• Language: English
• Subjects: Algorithms; Amino Acid Motifs; Amino acids; Animal models; Animals; Antibodies, Protozoan - immunology; Antigenicity; Antigens; Antigens, Protozoan - chemistry; Antigens, Protozoan - genetics; Antigens, Protozoan - immunology; Biochemistry; Bioinformatics; Biology and Life Sciences; Circular Dichroism; Computational Biology; Cross Reactions - immunology; Cross-reactivity; Databases, Genetic; Dichroism; Enzyme-linked immunosorbent assay; Epidemiology; Epitopes; Epitopes, T-Lymphocyte - chemistry; Epitopes, T-Lymphocyte - immunology; Female; Fragmentation; Fragments; Genome, Protozoan; Genomes; Histocompatibility Antigens Class II - immunology; Humans; Immunity, Cellular; Immunization; Immunogenicity; Immunoglobulin G - blood; Immunoglobulin G - immunology; Interferon; Leukocytes (mononuclear); Lymphocytes T; Malaria; Medicine and Health Sciences; Mice; Microorganisms; Neural networks; Parasites; Peptides; Peptides - chemistry; Peptides - immunology; Plasmodium falciparum; Plasmodium vivax; Plasmodium vivax - genetics; Plasmodium vivax - immunology; Polypeptides; Protein structure; Protein Structure, Secondary; Proteins; Public health; Vaccine development; Vaccines; Vector-borne diseases; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0100440

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.