title: Plasmodium vivax antigen discovery based on alpha-helical coiled coil protein motif.
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.
authors: Malaria Vaccine and Drug Development Center (MVDC), Cali, Colombia; School of Health, University of Valle, Cali, Colombia.
authors: Nora
authors: N
authors: Céspedes
authors: Biochemistry Department, University of Lausanne, Epalinges, Switzerland.
authors: Catherine
authors: C
authors: Habel
authors: Caucaseco Scientific Research Center, Cali, Colombia.
authors: Mary
authors: M
authors: Lopez-Perez
authors: Malaria Vaccine and Drug Development Center (MVDC), Cali, Colombia; Fundación Centro de Primates, Cali, Colombia.
authors: Angélica
authors: A
authors: Castellanos
authors: Centre de Recherches de Biochimie Macromoleculaire (CRBM) and Institut de Biologie Computationnelle (IBC), CNRS, University of Montpellier, Montpellier, France; University ITMO, St. Petersburg, Russia.
authors: Andrey V
authors: AV
authors: Kajava
authors: Biochemistry Department, University of Lausanne, Epalinges, Switzerland.
authors: Catherine
authors: C
authors: Servis
authors: Swiss Tropical and Public Health Institute, Basel, Switzerland.
authors: Ingrid
authors: I
authors: Felger
authors: Hôpital Saint Camille, Ouagadougou, Burkina Faso.
authors: Remy
authors: R
authors: Moret
authors: Malaria Vaccine and Drug Development Center (MVDC), Cali, Colombia; School of Health, University of Valle, Cali, Colombia.
authors: Myriam
authors: M
authors: Arévalo-Herrera
authors: Biochemistry Department, University of Lausanne, Epalinges, Switzerland.
authors: Giampietro
authors: G
authors: Corradin
authors: Malaria Vaccine and Drug Development Center (MVDC), Cali, Colombia; Caucaseco Scientific Research Center, Cali, Colombia.
authors: Sócrates
authors: S
authors: Herrera
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D002942:Circular Dichroism; D019295:Computational Biology; D003429:Cross Reactions / Q000276:immunology; D030541:Databases, Genetic; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D005260:Female; D018503:Genome, Protozoan; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D051379:Mice; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D010966:Plasmodium vivax / Q000235:genetics / Q000276:immunology*; D017433:Protein Structure, Secondary
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D010455:Peptides