title: Recombinant peptide replicates immunogenicity of synthetic linear peptide chimera for use as pre-erythrocytic stage malaria vaccine.
abstract: Synthetic linear peptide chimeras (LPCs(cys+)) show promise as delivery platforms for malaria subunit vaccines. Maximal immune response to LPCs(cys+) in rodent malaria models depends upon formation of cross-linkages to generate homopolymers, presenting challenges for vaccine production. To replicate the immunogenicity of LPCs(cys+) using a recombinant approach, we designed a recombinant LPC (rLPC) based on Plasmodium yoelii circumsporozoite protein-specific sequences of 208 amino acids consisting of four LPC subunits in series. BALB/c or CAF1/J mice were immunized with synthetic or recombinant LPCs. Antibody concentrations, cytokine production and protection against challenge were compared. Recombinant peptide replicated the robust, high avidity antibody responses obtained with the synthetic linear peptide chimera. After in vitro stimulation spleen cells from mice immunized with rLPC or synthetic LPC(cys+) produced gamma interferon and IL-4 suggesting the efficient priming of T cells. Immunization of mice with either recombinant or synthetic LPC(cys+) provided comparable protection against experimental challenge with P. yoelii sporozoites. Recombinant LPCs reproduced the immunogenicity of synthetic LPC(cys+) without requiring polymerization, improving prospects for use as malaria vaccines.
authors.affiliation: Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA.
authors.forename: Luciana M
authors.initials: LM
authors.lastname: Silva-Flannery
authors.forename: Monica
authors.initials: M
authors.lastname: Cabrera-Mora
authors.forename: Jianlin
authors.initials: J
authors.lastname: Jiang
authors.forename: Alberto
authors.initials: A
authors.lastname: Moreno
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D001483:Base Sequence; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D008288:Malaria / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D010967:Plasmodium yoelii / Q000276:immunology* / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D010455:Peptides; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C041595:circumsporozoite protein, Protozoan