| Author | Castro, Julia T. | |
| Author | Brito, Rory | |
| Author | Hojo-Souza, Natalia S. | |
| Author | Azevedo, Bárbara | |
| Author | Salazar, Natalia | |
| Author | Ferreira, Camila P. | |
| Author | Junqueira, Caroline | |
| Author | Fernandes, Ana Paula | |
| Author | Vasconcellos, Ronnie | |
| Author | Cardoso, Jamille M. | |
| Author | Soares, Rodrigo D. O. Aguiar | |
| Author | Vieira, Paula M. A. | |
| Author | Carneiro, Cláudia M. | |
| Author | Valiate, Bruno | |
| Author | Toledo, Cristiane | |
| Author | Salazar, Andres M. | |
| Author | Caballero, Otávia | |
| Author | Lannes-Vieira, Joseli | |
| Author | Teixeira, Santuza R. | |
| Author | Reis, Alexandre B. | |
| Author | Gazzinelli, Ricardo T. | |
| Access date | 2023-06-09T13:34:16Z | |
| Available date | 2023-06-09T13:34:16Z | |
| Document date | 2023 | |
| Citation | CASTRO, Julia T. et al. ASP-2/Trans-sialidase chimeric protein induces robust protective immunity in experimental models of Chagas’ disease. Vaccines, v. 8; 81, p. 1 - 14, 2023. | en_US |
| ISSN | 2076-393X | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/58983 | |
| Language | eng | en_US |
| Publisher | Nature | en_US |
| Rights | open access | |
| Subject in Portuguese | Doença de Chagas | en_US |
| Subject in Portuguese | Proteína quimérica ASP-2/Trans-sialidase | en_US |
| Subject in Portuguese | Induz imunidade protetora | en_US |
| Subject in Portuguese | Em modelos experimentais | en_US |
| Subject in Portuguese | Da doença de Chagas | en_US |
| Title | ASP-2/Trans-sialidase chimeric protein induces robust protective immunity in experimental models of Chagas’ disease | en_US |
| Type | Article | |
| Abstract | Immunization with the Amastigote Surface Protein-2 (ASP-2) and Trans-sialidase (TS) antigens either in the form of recombinant
protein, encoded in plasmids or human adenovirus 5 (hAd5) confers robust protection against various lineages of Trypanosoma
cruzi. Herein we generated a chimeric protein containing the most immunogenic regions for T and B cells from TS and ASP-2
(TRASP) and evaluated its immunogenicity in comparison with our standard protocol of heterologous prime-boost using plasmids
and hAd5. Mice immunized with TRASP protein associated to Poly-ICLC (Hiltonol) were highly resistant to challenge with T. cruzi,
showing a large decrease in tissue parasitism, parasitemia and no lethality. This protection lasted for at least 3 months after the last
boost of immunization, being equivalent to the protection induced by DNA/hAd5 protocol. TRASP induced high levels of T. cruzispecific
antibodies and IFNγ-producing T cells and protection was primarily mediated by CD8+ T cells and IFN-γ. We also evaluated
the toxicity, immunogenicity, and efficacy of TRASP and DNA/hAd5 formulations in dogs. Mild collateral effects were detected at
the site of vaccine inoculation. While the chimeric protein associated with Poly-ICLC induced high levels of antibodies and CD4+ T
cell responses, the DNA/hAd5 induced no antibodies, but a strong CD8+ T cell response. Immunization with either vaccine
protected dogs against challenge with T. cruzi. Despite the similar efficacy, we conclude that moving ahead with TRASP together
with Hiltonol is advantageous over the DNA/hAd5 vaccine due to pre-existing immunity to the adenovirus vector, as well as the
cost-benefit for development and large-scale production. | en_US |
| Affilliation | Centro de Tecnologia em Vacinas, Universidade Federal de Minas Gerais, Parque Tecnológico de Belo Horizonte, Belo Horizonte, Brasil / Centro de Pesquisas Rene Rachou. Fundação Osvaldo Cruz, Rio de Janeiro, Brasil / 3Plataforma de Medicina Translacional, Fundação Oswaldo Cruz-Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brasil. | en_US |
| Affilliation | Universidade Federal de Ouro Preto, Ouro Preto, MG, Brasil. | en_US |
| Affilliation | Centro de Tecnologia em Vacinas, Universidade Federal de Minas Gerais, Parque Tecnológico de Belo Horizonte, Belo Horizonte, Brasil / Fundação Osvaldo Cruz. Centro de Pesquisas Rene Rachou., Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Fundação Osvaldo Cruz. Centro de Pesquisas Rene Rachou., Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Centro de Tecnologia em Vacinas, Universidade Federal de Minas Gerais, Parque Tecnológico de Belo Horizonte, Belo Horizonte, Brasil. | en_US |
| Affilliation | Universidade Federal de São Paulo. São Paulo, SP, Brasil. | en_US |
| Affilliation | Centro de Tecnologia em Vacinas, Universidade Federal de Minas Gerais, Parque Tecnológico de Belo Horizonte, Belo Horizonte, Brasil / Fundação Osvaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Centro de Tecnologia em Vacinas, Universidade Federal de Minas Gerais, Parque Tecnológico de Belo Horizonte, Belo Horizonte, Brasil. | en_US |
| Affilliation | Universidade Federal de São Paulo, São Paulo, SP, Brasil. | en_US |
| Affilliation | Universidade Federal de Ouro Preto, Ouro Preto, MG, Brasil. | en_US |
| Affilliation | Universidade Federal de Ouro Preto, Ouro Preto, MG, Brasil. | en_US |
| Affilliation | Universidade Federal de Ouro Preto, Ouro Preto, MG, Brasil. | en_US |
| Affilliation | Universidade Federal de Ouro Preto, Ouro Preto, MG, Brasil. | en_US |
| Affilliation | Centro de Tecnologia em Vacinas, Universidade Federal de Minas Gerais, Parque Tecnológico de Belo Horizonte, Belo Horizonte, Brasil / Centro de Pesquisas Rene Rachou. Fundação Osvaldo Cruz, Rio de Janeiro, Brasil . | en_US |
| Affilliation | Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Oncovir, Inc, Washington, USA. | en_US |
| Affilliation | Orygen, LTDA, Sao Paulo, SP, Brasil. | en_US |
| Affilliation | Fundação Osvaldo Cruz, Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Centro de Tecnologia em Vacinas, Universidade Federal de Minas Gerais, Parque Tecnológico de Belo Horizonte, Belo Horizonte, Brasil. | en_US |
| Affilliation | Universidade Federal de Ouro Preto, Ouro Preto, MG, Brasil. | en_US |
| Affilliation | Centro de Tecnologia em Vacinas, Universidade Federal de Minas Gerais, Parque Tecnológico de Belo Horizonte, Belo Horizonte, Brasil / Centro de Pesquisas Rene Rachou. Fundação Osvaldo Cruz, Belo Horizonte, MG, Brasil / Plataforma de Medicina Translacional, Fundação Oswaldo Cruz-Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brasil. | en_US |
| Subject | Chagas disease | en_US |
| Subject | ASP-2/Trans-sialidase chimeric protein | en_US |
| Subject | Induces robust protective immunity | en_US |
| Subject | In experimental models | en_US |
| e-ISSN | 10.1038/s41541-023-00676-0 | |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
