title: A chimeric protein-based malaria vaccine candidate induces robust T cell responses against Plasmodium vivax MSP119.
abstract: The most widespread Plasmodium species, Plasmodium vivax, poses a significant public health threat. An effective vaccine is needed to reduce global malaria burden. Of the erythrocytic stage vaccine candidates, the 19 kDa fragment of the P. vivax Merozoite Surface Protein 1 (PvMSP119) is one of the most promising. Our group has previously defined several promiscuous T helper epitopes within the PvMSP1 protein, with features that allow them to bind multiple MHC class II alleles. We describe here a P. vivax recombinant modular chimera based on MSP1 (PvRMC-MSP1) that includes defined T cell epitopes genetically fused to PvMSP119. This vaccine candidate preserved structural elements of the native PvMSP119and elicited cytophilic antibody responses, and CD4+ and CD8+ T cells capable of recognizing PvMSP119. Although CD8+ T cells that recognize blood stage antigens have been reported to control blood infection, CD8+ T cell responses induced by P. falciparum or P. vivax vaccine candidates based on MSP119have not been reported. To our knowledge, this is the first time a protein based subunit vaccine has been able to induce CD8+ T cell against PvMSP119. The PvRMC-MSP1 protein was also recognized by naturally acquired antibodies from individuals living in malaria endemic areas with an antibody profile associated with protection from infection. These features make PvRMC-MSP1 a promising vaccine candidate.
authors.affiliation: Emory Vaccine Center, YerkesNational Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA.|Division of Infectious Diseases, Department of Medicine, Emory University, 69 Jesse Hill, Jr. Drive, SE, Atlanta, GA 30303, USA.
authors.forename: Jairo Andres
authors.initials: JA
authors.lastname: Fonseca
authors.affiliation: Emory Vaccine Center, YerkesNational Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Cabrera-Mora
authors.affiliation: Emory Vaccine Center, YerkesNational Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA.
authors.forename: Balwan
authors.initials: B
authors.lastname: Singh
authors.affiliation: Laboratory of Immunoparasitology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, (FIOCRUZ), Rio de Janeiro, RJ, Brazil.
authors.forename: Joseli
authors.initials: J
authors.lastname: Oliveira-Ferreira
authors.affiliation: Laboratory of Immunoparasitology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, (FIOCRUZ), Rio de Janeiro, RJ, Brazil.
authors.forename: Josué
authors.initials: J
authors.lastname: da Costa Lima-Junior
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: J Mauricio
authors.initials: JM
authors.lastname: Calvo-Calle
authors.affiliation: Molecular Mimetism of Infectious Agents Unit, Department of Pharmacy, Universidad Nacional de Colombia, Bogota, Colombia.
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Lozano
authors.affiliation: Emory Vaccine Center, YerkesNational Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA.|Division of Infectious Diseases, Department of Medicine, Emory University, 69 Jesse Hill, Jr. Drive, SE, Atlanta, GA 30303, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Moreno
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D017780:Malaria Vaccines / Q000276:immunology*; D016780:Malaria, Vivax / Q000276:immunology / Q000517:prevention & control; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010966:Plasmodium vivax / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D000939:Epitopes; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D011993:Recombinant Fusion Proteins