Vaccine Containing the Three Allelic Variants of the Plasmodium vivax Circumsporozoite Antigen Induces Protection in Mice after Challenge with a Transgenic Rodent Malaria Parasite

Vaccine Containing the Three Allelic Variants of the Plasmodium vivax Circumsporozoite Antigen Induces Protection in Mice after Challenge with a Transgenic Rodent Malaria Parasite

Author Gimenez, Alba Marina Autor UNIFESP Google Scholar
Lima, Luciana Chagas [UNIFESP Google Scholar
Francoso, Katia Sanches Google Scholar
Denapoli, Priscila M. A. [UNIFESP Google Scholar
Panatieri, Raquel Google Scholar
Bargieri, Daniel Y. Google Scholar
Thiberge, Jean-Michel Google Scholar
Andolina, Chiara Google Scholar
Nosten, Francois Google Scholar
Renia, Laurent Google Scholar
Nussenzweig, Ruth S. Google Scholar
Nussenzweig, Victor Google Scholar
Amino, Rogerio Google Scholar
Rodrigues, Mauricio M. [UNIFESP Google Scholar
Soares, Irene S. Google Scholar
Abstract Plasmodium vivax is the most common species that cause malaria outside of the African continent. The development of an efficacious vaccine would contribute greatly to control malaria. Recently, using bacterial and adenoviral recombinant proteins based on the P. vivax circumsporozoite protein (CSP), we demonstrated the possibility of eliciting strong antibody-mediated immune responses to each of the three allelic forms of P. vivax CSP (PvCSP). In the present study, recombinant proteins representing the PvCSP alleles (VK210, VK247, and P. vivax-like), as well as a hybrid polypeptide, named PvCSP-All epi-topes, were generated. This hybrid containing the conserved C-terminal of the PvCSP and the three variant repeat domains in tandem were successfully produced in the yeast Pichia pastoris. After purification and biochemical characterization, they were used for the experimental immunization of C57BL/6 mice in a vaccine formulation containing the adjuvant Poly(I: C). Immunization with a recombinant protein expressing all three different allelic forms in fusion elicited high IgG antibody titers reacting with all three different allelic variants of PvCSP. The antibodies targeted both the C-terminal and repeat domains of PvCSP and recognized the native protein on the surface of P. vivax sporozoites. More importantly, mice that received the vaccine formulation were protected after challenge with chimeric Plasmodium berghei sporozoites expressing CSP repeats of P. vivax sporozoites (Pb/PvVK210). Our results suggest that it is possible to elicit protective immunity against one of the most common PvCSP alleles using soluble recombinant proteins expressed by P. pastoris. These recombinant proteins are promising candidates for clinical trials aiming to develop a multiallele vaccine against P. vivax malaria.
Keywords malaria
Plasmodium vivax
recombinant vaccine
circumsporozoite protein
prime-boost regimens
xmlui.dri2xhtml.METS-1.0.item-coverage Lausanne
Language English
Sponsor Fundacao de Amparo a Pesquisa do Estado de Sao Paulo
Instituto Nacional de Ciencia e Tecnologia de Vacinas (INCTV-CNPq)
FAPESP
CAPES
CNPq
Wellcome Trust]
Wellcome Trust
Singapore Immunology Network (SIgN)
Agency for Science, Technology and Research (A* STAR, Singapore)
Grant number FAPESP: 2012/13032-5
Date 2017
Published in Frontiers In Immunology. Lausanne, v. 8, p. -, 2017.
ISSN 1664-3224 (Sherpa/Romeo, impact factor)
Publisher Frontiers Media Sa
Extent -
Origin http://dx.doi.org/10.3389/fimmu.2017.01275
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000412732100001
URI https://repositorio.unifesp.br/handle/11600/57153

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