Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/13648
Title: Induction of Multifunctional Broadly Reactive T Cell Responses by a Plasmodium vivax Circumsporozoite Protein Recombinant Chimera
Authors: Cabrera-Mora, Monica
Fonseca, Jairo Andres
Singh, Balwan
Ferreira, Joseli Oliveira
Lima Junior, Josué da Costa
Calvo-Calle, J. Mauricio
Moreno, Alberto
Affilliation: Emory University. Yerkes National Primate Research Center. Emory Vaccine Center. Atlanta, GA, USA.
Emory University. Yerkes National Primate Research Center. Emory Vaccine Center. Atlanta, GA, USA.
Emory University. Yerkes National Primate Research Center. Emory Vaccine Center. Atlanta, GA, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil.
University of Massachusetts Medical School. Department of Pathology. Massachusetts, USA.
Emory University. Yerkes National Primate Research Center. Emory Vaccine Center. Atlanta, GA, USA / Emory University. Department of Medicine. Division of Infectious Disease. Atlanta, GA, USA.
Abstract: Plasmodium vivax is the most widespread species of Plasmodium, causing up to 50% of the malaria cases occurring outside subSaharan Africa. An effective vaccine is essential for successful control and potential eradication. A well-characterized vaccine candidate is the circumsporozoite protein (CSP). Preclinical and clinical trials have shown that both antibodies and cellular immune responses have been correlated with protection induced by immunization with CSP. On the basis of our reported approach of developing chimeric Plasmodium yoelii proteins to enhance protective efficacy, we designed PvRMC-CSP, a recombinant chimeric protein based on the P. vivax CSP (PvCSP). In this engineered protein, regions of the PvCSP predicted to contain human T cell epitopes were genetically fused to an immunodominant B cell epitope derived from the N-terminal region I and to repeat sequences representing the two types of PvCSP repeats. The chimeric protein was expressed in soluble form with high yield. As the immune response to PvCSP has been reported to be genetically restricted in the murine model, we tested the immunogenicity of PvRMC-CSP in groups of six inbred strains of mice. PvRMC-CSP was able to induce robust antibody responses in all the mouse strains tested. Synthetic peptides representing the allelic forms of the P. vivax CSP were also recognized to a similar extent regardless of the mouse strain. Furthermore, the immunization regimen induced high frequencies of multifunctional CD4 and CD8 PvRMC-CSP-specific T cells. The depth and breadth of the immune responses elicited suggest that immunization with PvRMC-CSP can circumvent the genetic restriction of the immune response to P. vivax CSP. Interestingly, PvRMCCSP was also recognized by naturally acquired antibodies from individuals living in areas where malaria is endemic. These features make PvRMC-CSP a promising vaccine candidate for further development.
Keywords: Plasmodium vivax
Quimera
Malaria
Vacina
Proteínas Recombinantes
DeCS: Plasmodium vivax
Chimera
Malária
Circumsporozoite Protein
Vaccine
Recombinant Proteins
Issue Date: 2015
Publisher: American Society for Microbiology
Citation: CABRERA-MORA, Monica; et al. Induction of Multifunctional Broadly Reactive T Cell Responses by a Plasmodium vivax Circumsporozoite Protein Recombinant Chimera. Infection and Immunity, v.83, n.9, p.3749-3761, Sept. 2015.
DOI: 10.1128/IAI.00480-15
ISSN: 0019-9567
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

Files in This Item:
File Description SizeFormat 
joseli_ferreira_etal_IOC_2015.pdf1.72 MBAdobe PDFView/Open



FacebookTwitterDeliciousLinkedInGoogle BookmarksBibTex Format mendeley Endnote DiggMySpace

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.