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

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),...

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Main Authors: Alba Marina Gimenez, Luciana Chagas Lima, Katia Sanches Françoso, Priscila M. A. Denapoli, Raquel Panatieri, Daniel Y. Bargieri, Jean-Michel Thiberge, Chiara Andolina, Francois Nosten, Laurent Renia, Ruth S. Nussenzweig, Victor Nussenzweig, Rogerio Amino, Mauricio M. Rodrigues, Irene S. Soares
Format: Article
Language:English
Published: Frontiers Media S.A. 2017-10-01
Series:Frontiers in Immunology
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fimmu.2017.01275/full
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author Alba Marina Gimenez
Luciana Chagas Lima
Luciana Chagas Lima
Katia Sanches Françoso
Priscila M. A. Denapoli
Raquel Panatieri
Raquel Panatieri
Daniel Y. Bargieri
Jean-Michel Thiberge
Chiara Andolina
Chiara Andolina
Francois Nosten
Francois Nosten
Laurent Renia
Ruth S. Nussenzweig
Victor Nussenzweig
Rogerio Amino
Mauricio M. Rodrigues
Irene S. Soares
spellingShingle Alba Marina Gimenez
Luciana Chagas Lima
Luciana Chagas Lima
Katia Sanches Françoso
Priscila M. A. Denapoli
Raquel Panatieri
Raquel Panatieri
Daniel Y. Bargieri
Jean-Michel Thiberge
Chiara Andolina
Chiara Andolina
Francois Nosten
Francois Nosten
Laurent Renia
Ruth S. Nussenzweig
Victor Nussenzweig
Rogerio Amino
Mauricio M. Rodrigues
Irene S. Soares
Vaccine Containing the Three Allelic Variants of the Plasmodium vivax Circumsporozoite Antigen Induces Protection in Mice after Challenge with a Transgenic Rodent Malaria Parasite
Frontiers in Immunology
malaria
Plasmodium vivax
recombinant vaccine
circumsporozoite protein
prime-boost regimens
author_facet Alba Marina Gimenez
Luciana Chagas Lima
Luciana Chagas Lima
Katia Sanches Françoso
Priscila M. A. Denapoli
Raquel Panatieri
Raquel Panatieri
Daniel Y. Bargieri
Jean-Michel Thiberge
Chiara Andolina
Chiara Andolina
Francois Nosten
Francois Nosten
Laurent Renia
Ruth S. Nussenzweig
Victor Nussenzweig
Rogerio Amino
Mauricio M. Rodrigues
Irene S. Soares
author_sort Alba Marina Gimenez
title Vaccine Containing the Three Allelic Variants of the Plasmodium vivax Circumsporozoite Antigen Induces Protection in Mice after Challenge with a Transgenic Rodent Malaria Parasite
title_short Vaccine Containing the Three Allelic Variants of the Plasmodium vivax Circumsporozoite Antigen Induces Protection in Mice after Challenge with a Transgenic Rodent Malaria Parasite
title_full Vaccine Containing the Three Allelic Variants of the Plasmodium vivax Circumsporozoite Antigen Induces Protection in Mice after Challenge with a Transgenic Rodent Malaria Parasite
title_fullStr Vaccine Containing the Three Allelic Variants of the Plasmodium vivax Circumsporozoite Antigen Induces Protection in Mice after Challenge with a Transgenic Rodent Malaria Parasite
title_full_unstemmed Vaccine Containing the Three Allelic Variants of the Plasmodium vivax Circumsporozoite Antigen Induces Protection in Mice after Challenge with a Transgenic Rodent Malaria Parasite
title_sort vaccine containing the three allelic variants of the plasmodium vivax circumsporozoite antigen induces protection in mice after challenge with a transgenic rodent malaria parasite
publisher Frontiers Media S.A.
series Frontiers in Immunology
issn 1664-3224
publishDate 2017-10-01
description 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 epitopes, 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.
topic malaria
Plasmodium vivax
recombinant vaccine
circumsporozoite protein
prime-boost regimens
url http://journal.frontiersin.org/article/10.3389/fimmu.2017.01275/full
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spelling doaj-697801f110034793978b27aca485aa052020-11-24T22:29:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-10-01810.3389/fimmu.2017.01275283943Vaccine Containing the Three Allelic Variants of the Plasmodium vivax Circumsporozoite Antigen Induces Protection in Mice after Challenge with a Transgenic Rodent Malaria ParasiteAlba Marina Gimenez0Luciana Chagas Lima1Luciana Chagas Lima2Katia Sanches Françoso3Priscila M. A. Denapoli4Raquel Panatieri5Raquel Panatieri6Daniel Y. Bargieri7Jean-Michel Thiberge8Chiara Andolina9Chiara Andolina10Francois Nosten11Francois Nosten12Laurent Renia13Ruth S. Nussenzweig14Victor Nussenzweig15Rogerio Amino16Mauricio M. Rodrigues17Irene S. Soares18Department of Microbiology, Immunology and Parasitology, Center of Cellular and Molecular Therapy (CTCMol), Federal University of São Paulo, São Paulo, BrazilDepartment of Microbiology, Immunology and Parasitology, Center of Cellular and Molecular Therapy (CTCMol), Federal University of São Paulo, São Paulo, BrazilDepartment of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, São Paulo, BrazilDepartment of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, São Paulo, BrazilDepartment of Microbiology, Immunology and Parasitology, Center of Cellular and Molecular Therapy (CTCMol), Federal University of São Paulo, São Paulo, BrazilUnit of Malaria Infection and Immunity, Institut Pasteur, Paris, FranceDepartment of Parasitology, University of São Paulo, São Paulo, BrazilDepartment of Parasitology, University of São Paulo, São Paulo, BrazilUnit of Malaria Infection and Immunity, Institut Pasteur, Paris, FranceShoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, ThailandCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research Building, University of Oxford, Oxford, United KingdomShoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, ThailandCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research Building, University of Oxford, Oxford, United KingdomSingapore Immunology Network, Biopolis, Agency for Science Technology and Research, Singapore, SingaporeNew York University School of Medicine, New York, NY, United StatesNew York University School of Medicine, New York, NY, United StatesUnit of Malaria Infection and Immunity, Institut Pasteur, Paris, FranceDepartment of Microbiology, Immunology and Parasitology, Center of Cellular and Molecular Therapy (CTCMol), Federal University of São Paulo, São Paulo, BrazilDepartment of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, São Paulo, BrazilPlasmodium 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 epitopes, 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.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01275/fullmalariaPlasmodium vivaxrecombinant vaccinecircumsporozoite proteinprime-boost regimens