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

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

Autor Nogueira, Raquel Tayar Google Scholar
Nogueira, Alanderson Rocha Google Scholar
Souza Pereira, Mirian Claudia Google Scholar
Rodrigues, Mauricio Martins Autor UNIFESP Google Scholar
Costa Neves, Patricia Cristina da Google Scholar
Galler, Ricardo Google Scholar
Bonaldo, Myrna Cristina Google Scholar
Instituição Fundacao Oswaldo Cruz
Universidade Federal de São Paulo (UNIFESP)
Resumo 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.
Idioma Inglês
Financiador Fundacao de Amparo a Pesquisa do Estado de Rio de Janeiro
National Institute for Vaccine Science and Technology
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
FIOCRUZ
Data de publicação 2013-03-19
Publicado em Plos One. San Francisco: Public Library Science, v. 8, n. 3, 13 p., 2013.
ISSN 1932-6203 (Sherpa/Romeo, fator de impacto)
Publicador Public Library Science
Extensão 13
Fonte http://dx.doi.org/10.1371/journal.pone.0059347
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000317562100113
Endereço permanente http://repositorio.unifesp.br/handle/11600/36091

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