Protective immunity against Trypanosoma cruzi infection in a highly susceptible mouse strain after vaccination with genes encoding the amastigote surface protein-2 and trans-sialidase

Protective immunity against Trypanosoma cruzi infection in a highly susceptible mouse strain after vaccination with genes encoding the amastigote surface protein-2 and trans-sialidase

Autor Vasconcelos, JR Google Scholar
Hiyane, M. I. Google Scholar
Marinho, CRF Google Scholar
Claser, C. Google Scholar
Machado, AMV Google Scholar
Gazzinelli, R. T. Google Scholar
Bruna-Romero, O. Google Scholar
Alvarez, J. M. Google Scholar
Boscardin, S. B. Google Scholar
Rodrigues, M. M. Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Universidade Federal de Minas Gerais (UFMG)
Fiocruz MS
Resumo Protective immunity against lethal infection is developed when BALB/c or C57BL/6 mice are immunized with plasmids containing genes from the protozoan parasite Trypanosoma cruzi. However, genetic vaccination of the highly susceptible mouse strain A/Sn promoted limited survival after challenge. This observation questioned whether this type of vaccination would be appropriate for highly susceptible individuals. Here, we compared the protective efficacy and the immune response after individual or combined genetic vaccination of A/Sn mice with genes encoding trans-sialidase (TS) or the amastigote surface protein-2 (ASP-2). After challenge, a significant proportion of A/Sn mice immunized with either the asp-2 gene or simultaneously with asp-2 and ts genes, survived infection. in contrast, the vast majority of mice immunized with the ts gene or the vector alone died. Parasitological and histological studies performed in the surviving mice revealed that these mice harbored parasites; however, minimal inflammatory responses were seen in heart and striated muscle. We used this model to search for an in vitro correlation for protection. We found that protective immunity correlated with a higher secretion of interferon-gamma by spleen cells on in vitro restimulation with ASP-2 and the presence of ASP-2-specific CD8 cells. Depletion of either CD4 or CD8 or both T-cell subpopulations prior to the challenge rendered the mice susceptible to infection demonstrating the critical contribution of both cell types in protective immunity. Our results reinforce the prophylactic potential of genetic vaccination with asp-2 and ts genes by describing protective immunity against lethal T. cruzi infection and chronic tissue pathology in a highly susceptible mouse strain.
Idioma Inglês
Data de publicação 2004-09-01
Publicado em Human Gene Therapy. Larchmont: Mary Ann Liebert Inc Publ, v. 15, n. 9, p. 878-886, 2004.
ISSN 1043-0342 (Sherpa/Romeo, fator de impacto)
Publicador Mary Ann Liebert Inc Publ
Extensão 878-886
Fonte http://dx.doi.org/10.1089/hum.2004.15.878
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000223831300006
Endereço permanente http://repositorio.unifesp.br/handle/11600/27926

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