Recombinant Yellow Fever Viruses Elicit CD8(+) T Cell Responses and Protective Immunity against Trypanosoma cruzi

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dc.contributor.author Nogueira, Raquel Tayar
dc.contributor.author Nogueira, Alanderson Rocha
dc.contributor.author Souza Pereira, Mirian Claudia
dc.contributor.author Rodrigues, Mauricio Martins [UNIFESP]
dc.contributor.author Costa Neves, Patricia Cristina da
dc.contributor.author Galler, Ricardo
dc.contributor.author Bonaldo, Myrna Cristina
dc.date.accessioned 2016-01-24T14:31:25Z
dc.date.available 2016-01-24T14:31:25Z
dc.date.issued 2013-03-19
dc.identifier http://dx.doi.org/10.1371/journal.pone.0059347
dc.identifier.citation Plos One. San Francisco: Public Library Science, v. 8, n. 3, 13 p., 2013.
dc.identifier.issn 1932-6203
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/36091
dc.description.abstract Chagas' disease is a major public health problem affecting nearly 10 million in Latin America. Despite several experimental vaccines have shown to be immunogenic and protective in mouse models, there is not a current vaccine being licensed for humans or in clinical trial against T. cruzi infection. Towards this goal, we used the backbone of Yellow Fever (YF) 17D virus, one of the most effective and well-established human vaccines, to express an immunogenic fragment derived from T. cruzi Amastigote Surface Protein 2 (ASP-2). the cDNA sequence of an ASP-2 fragment was inserted between E and NS1 genes of YF 17D virus through the construction of a recombinant heterologous cassette. the replication ability and genetic stability of recombinant YF virus (YF17D/ENS1/Tc) was confirmed for at least six passages in Vero cells. Immunogenicity studies showed that YF17D/ENS1/Tc virus elicited neutralizing antibodies and gamma interferon (IFN-gamma) producing-cells against the YF virus. Also, it was able to prime a CD8(+) T cell directed against the transgenic T. cruzi epitope (TEWETGQI) which expanded significantly as measured by T cell-specific production of IFN-gamma before and after T. cruzi challenge. However, most important for the purposes of vaccine development was the fact that a more efficient protective response could be seen in mice challenged after vaccination with the YF viral formulation consisting of YF17D/ENS1/Tc and a YF17D recombinant virus expressing the TEWETGQI epitope at the NS2B-3 junction. the superior protective immunity observed might be due to an earlier priming of epitope-specific IFN-gamma-producing T CD8(+) cells induced by vaccination with this viral formulation. Our results suggest that the use of viral formulations consisting of a mixture of recombinant YF 17D viruses may be a promising strategy to elicit protective immune responses against pathogens, in general. en
dc.description.sponsorship Fundacao de Amparo a Pesquisa do Estado de Rio de Janeiro
dc.description.sponsorship National Institute for Vaccine Science and Technology
dc.description.sponsorship Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorship FIOCRUZ
dc.format.extent 13
dc.language.iso eng
dc.publisher Public Library Science
dc.relation.ispartof Plos One
dc.rights Acesso aberto
dc.title Recombinant Yellow Fever Viruses Elicit CD8(+) T Cell Responses and Protective Immunity against Trypanosoma cruzi en
dc.type Artigo
dc.contributor.institution Fundacao Oswaldo Cruz
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.description.affiliation Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Lab Biol Mol Flavivirus, Rio de Janeiro, Brazil
dc.description.affiliation Fundacao Oswaldo Cruz, Inst Tecnol & Imunobiol, Rio de Janeiro, Brazil
dc.description.affiliation Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Lab Ultra Estrutura Celular, Rio de Janeiro, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, Ctr Terapia Celular & Mol, São Paulo, Brazil
dc.description.affiliation Fundacao Oswaldo Cruz, Inst Tecnol & Imunobiol, Lab Tecnol Imunol, Rio de Janeiro, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, Ctr Terapia Celular & Mol, São Paulo, Brazil
dc.identifier.file WOS000317562100113.pdf
dc.identifier.doi 10.1371/journal.pone.0059347
dc.description.source Web of Science
dc.identifier.wos WOS:000317562100113



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