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INDUCTION OF MULTIFUNCTIONAL BROADLY REACTIVE T CELL RESPONSES BY A PLASMODIUM VIVAX CIRCUMSPOROZOITE PROTEIN RECOMBINANT CHIMERA
Author
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.
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.
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