title: Genetic vaccination against experimental infection with myotropic parasite strains of Trypanosoma cruzi.
abstract: In earlier studies, we reported that a heterologous prime-boost regimen using recombinant plasmid DNA followed by replication-defective adenovirus vector, both containing Trypanosoma cruzi genes encoding trans-sialidase (TS) and amastigote surface protein (ASP) 2, provided protective immunity against experimental infection with a reticulotropic strain of this human protozoan parasite. Herein, we tested the outcome of genetic vaccination of F1 (CB10XBALB/c) mice challenged with myotropic parasite strains (Brazil and Colombian). Initially, we determined that the coadministration during priming of a DNA plasmid containing the murine IL-12 gene improved the immune response and was essential for protective immunity elicited by the heterologous prime-boost regimen in susceptible male mice against acute lethal infections with these parasites. The prophylactic or therapeutic vaccination of resistant female mice led to a drastic reduction in the number of inflammatory infiltrates in cardiac and skeletal muscles during the chronic phase of infection with either strain. Analysis of the electrocardiographic parameters showed that prophylactic vaccination reduced the frequencies of sinus arrhythmia and atrioventricular block. Our results confirmed that prophylactic vaccination using the TS and ASP-2 genes benefits the host against acute and chronic pathologies caused by T. cruzi and should be further evaluated for the development of a veterinary or human vaccine against Chagas disease.
authors: Centro de Terapia Celular e Molecular (CTCMol), Escola Paulista de Medicina, UNIFESP, Rua Mirassol, 207 04044-010 São Paulo, SP, Brazil ; Departmento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Mirassol, 207 04044-010 São Paulo, SP, Brazil.
authors: Adriano Fernando
authors: AF
authors: Araújo
authors: Laboratório Biologia Celular, Instituto Oswaldo Cruz (FIOCRUZ), Avenida Brasil, 4365-Manguinhos, 21040-360 Rio de Janeiro, RJ, Brazil.
authors: Gabriel
authors: G
authors: de Oliveira
authors: Centro de Pesquisas Gonçalo Moniz, FIOCRUZ, Rua Waldemar Falcão, 121, 40296-710 Salvador, BA, Brazil ; Hospital São Rafael, Avenida São Rafael 2152, São Marcos, 41253-190 Salvador, BA, Brazil.
authors: Juliana Fraga
authors: JF
authors: Vasconcelos
authors: Centro de Terapia Celular e Molecular (CTCMol), Escola Paulista de Medicina, UNIFESP, Rua Mirassol, 207 04044-010 São Paulo, SP, Brazil ; Departmento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Mirassol, 207 04044-010 São Paulo, SP, Brazil.
authors: Jonatan
authors: J
authors: Ersching
authors: Centro de Terapia Celular e Molecular (CTCMol), Escola Paulista de Medicina, UNIFESP, Rua Mirassol, 207 04044-010 São Paulo, SP, Brazil ; Departmento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Mirassol, 207 04044-010 São Paulo, SP, Brazil.
authors: Mariana Ribeiro
authors: MR
authors: Dominguez
authors: Centro de Terapia Celular e Molecular (CTCMol), Escola Paulista de Medicina, UNIFESP, Rua Mirassol, 207 04044-010 São Paulo, SP, Brazil ; Departmento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Mirassol, 207 04044-010 São Paulo, SP, Brazil ; Departamento de Biociências, Instituto de Saúde e Sociedade, UNIFESP, Campus Baixada Santista, 11015-020 Santos, SP, Brazil.
authors: José Ronnie
authors: JR
authors: Vasconcelos
authors: Centro de Pesquisas René Rachou, FIOCRUZ, Avenida Augusto de Lima 1.715, Barro Preto, 30190-002 Belo Horizonte, MG, Brazil.
authors: Alexandre Vieira
authors: AV
authors: Machado
authors: Centro de Pesquisas René Rachou, FIOCRUZ, Avenida Augusto de Lima 1.715, Barro Preto, 30190-002 Belo Horizonte, MG, Brazil ; Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Presidente Antônio Carlos, 6627, Pampulha, 31270-901 Belo Horizonte, MG, Brazil ; Division of Infectious Disease and Immunology, Department of Medicine, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
authors: Ricardo Tostes
authors: RT
authors: Gazzinelli
authors: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Campus Universitário da Trindade, 88040-900 Florianopolis, SC, Brazil.
authors: Oscar
authors: O
authors: Bruna-Romero
authors: Centro de Pesquisas Gonçalo Moniz, FIOCRUZ, Rua Waldemar Falcão, 121, 40296-710 Salvador, BA, Brazil ; Hospital São Rafael, Avenida São Rafael 2152, São Marcos, 41253-190 Salvador, BA, Brazil.
authors: Milena Botelho
authors: MB
authors: Soares
authors: Centro de Terapia Celular e Molecular (CTCMol), Escola Paulista de Medicina, UNIFESP, Rua Mirassol, 207 04044-010 São Paulo, SP, Brazil ; Departmento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Mirassol, 207 04044-010 São Paulo, SP, Brazil.
authors: Mauricio Martins
authors: MM
authors: Rodrigues
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D014355:Chagas Disease / Q000517:prevention & control; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000235:genetics / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity*
chemical_list: D006023:Glycoproteins; D018664:Interleukin-12; C069715:trans-sialidase; C493236:ASP-2 protein, Trypanosoma cruzi; D009439:Neuraminidase