A Human Type 5 Adenovirus-Based Trypanosoma cruzi Therapeutic Vaccine Re-programs Immune Response and Reverses Chronic Cardiomyopathy
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2015 |
| Outros Autores: | , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/12415 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil |
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Pereira, Isabela ResendePereira, Glaucia VilarMarques, VirgíniaSilva, Andrea Alice daCaetano, BráuliaMoreira, Otacilio CruzMachado, Alexandre VieiraRomero, Oscar BrunaRodrigues, Maurício MartinsGazzinelli, Ricardo TostesVieira, Joseli Lannes2015-12-15T13:56:01Z2015-12-15T13:56:01Z2015PEREIRA, Isabela Resende et al. A Human Type 5 Adenovirus-Based Trypanosoma cruzi Therapeutic Vaccine Re-programs Immune Response and Reverses Chronic Cardiomyopathy. PLoS Pathog, vol. 11, n. 1, p. e1004594, 2015.1553-7366https://www.arca.fiocruz.br/handle/icict/1241510.1371/journal.ppat.1004594engPublic Library of ScienceA Human Type 5 Adenovirus-Based Trypanosoma cruzi Therapeutic Vaccine Re-programs Immune Response and Reverses Chronic Cardiomyopathyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, BrasilUniversidade Federal Fluminense. Departamento de Patologia. Niterói, RJ, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil /Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil/Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e do Sarampo. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, BrasilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, BrazilUniversidade Federal de Santa Catarina. Departamento de Microbiologia, Imunologia e Parasitologia. Florianópolis, SC, BrazilUniversidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil/ Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil/University of Massachusetts Medical School. Department of Medicine. Division of Infectious Disease and Immunology. Worcester, MA, United States of AmericaFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, BrasilChagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a prototypical neglected tropical disease. Specific immunity promotes acute phase survival. Nevertheless, one-third of CD patients develop chronic chagasic cardiomyopathy (CCC) associated with parasite persistence and immunological unbalance. Currently, the therapeutic management of patients only mitigates CCC symptoms. Therefore, a vaccine arises as an alternative to stimulate protective immunity and thereby prevent, delay progression and even reverse CCC. We examined this hypothesis by vaccinating mice with replication-defective human Type 5 recombinant adenoviruses (rAd) carrying sequences of amastigote surface protein-2 (rAdASP2) and trans-sialidase (rAdTS) T. cruzi antigens. For prophylactic vaccination, naïve C57BL/6 mice were immunized with rAdASP2+rAdTS (rAdVax) using a homologous prime/boost protocol before challenge with the Colombian strain. For therapeutic vaccination, rAdVax administration was initiated at 120 days post-infection (dpi), when mice were afflicted by CCC. Mice were analyzed for electrical abnormalities, immune response and cardiac parasitism and tissue damage. Prophylactic immunization with rAdVax induced antibodies and H-2Kb-restricted cytotoxic and interferon (IFN)γ-producing CD8+ T-cells, reduced acute heart parasitism and electrical abnormalities in the chronic phase. Therapeutic vaccination increased survival and reduced electrical abnormalities after the prime (analysis at 160 dpi) and the boost (analysis at 180 and 230 dpi). Post-therapy mice exhibited less heart injury and electrical abnormalities compared with pre-therapy mice. rAdVax therapeutic vaccination preserved specific IFNγ-mediated immunity but reduced the response to polyclonal stimuli (anti-CD3 plus anti-CD28), CD107a+ CD8+ T-cell frequency and plasma nitric oxide (NO) levels. Moreover, therapeutic rAdVax reshaped immunity in the heart tissue as reduced the number of perforin+ cells, preserved the number of IFNγ+ cells, increased the expression of IFNγ mRNA but reduced inducible NO synthase mRNA. Vaccine-based immunostimulation with rAd might offer a rational alternative for re-programming the immune response to preserve and, moreover, recover tissue injury in Chagas’ heart disease.CD8-Positive T-Lymphocytes/immunologyChagas Cardiomyopathy/prevention & controlImmune System ProcessesVaccines, DNA/geneticsinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/12415/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALA Human Type 5 Adenovirus-Based Trypanosoma cruzi Therapeutic Vaccine Re-programs Immune Response and Reverses Chronic Cardiomy.pdfA Human Type 5 Adenovirus-Based Trypanosoma cruzi Therapeutic Vaccine Re-programs Immune Response and Reverses Chronic Cardiomy.pdfapplication/pdf651747https://www.arca.fiocruz.br/bitstream/icict/12415/2/A%20Human%20Type%205%20Adenovirus-Based%20Trypanosoma%20cruzi%20Therapeutic%20Vaccine%20Re-programs%20Immune%20Response%20and%20Reverses%20Chronic%20Cardiomy.pdf8d67724350fdf9b840414b5109c764cbMD52TEXTA Human Type 5 Adenovirus-Based Trypanosoma cruzi Therapeutic Vaccine Re-programs Immune Response and Reverses Chronic Cardiomy.pdf.txtA Human Type 5 Adenovirus-Based Trypanosoma cruzi Therapeutic Vaccine Re-programs Immune Response and Reverses Chronic Cardiomy.pdf.txtExtracted texttext/plain90009https://www.arca.fiocruz.br/bitstream/icict/12415/3/A%20Human%20Type%205%20Adenovirus-Based%20Trypanosoma%20cruzi%20Therapeutic%20Vaccine%20Re-programs%20Immune%20Response%20and%20Reverses%20Chronic%20Cardiomy.pdf.txtb9ab0901b383abd250daf9b25dda5971MD53icict/124152019-06-19 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| dc.title.pt_BR.fl_str_mv |
A Human Type 5 Adenovirus-Based Trypanosoma cruzi Therapeutic Vaccine Re-programs Immune Response and Reverses Chronic Cardiomyopathy |
| title |
A Human Type 5 Adenovirus-Based Trypanosoma cruzi Therapeutic Vaccine Re-programs Immune Response and Reverses Chronic Cardiomyopathy |
| spellingShingle |
A Human Type 5 Adenovirus-Based Trypanosoma cruzi Therapeutic Vaccine Re-programs Immune Response and Reverses Chronic Cardiomyopathy Pereira, Isabela Resende CD8-Positive T-Lymphocytes/immunology Chagas Cardiomyopathy/prevention & control Immune System Processes Vaccines, DNA/genetics |
| title_short |
A Human Type 5 Adenovirus-Based Trypanosoma cruzi Therapeutic Vaccine Re-programs Immune Response and Reverses Chronic Cardiomyopathy |
| title_full |
A Human Type 5 Adenovirus-Based Trypanosoma cruzi Therapeutic Vaccine Re-programs Immune Response and Reverses Chronic Cardiomyopathy |
| title_fullStr |
A Human Type 5 Adenovirus-Based Trypanosoma cruzi Therapeutic Vaccine Re-programs Immune Response and Reverses Chronic Cardiomyopathy |
| title_full_unstemmed |
A Human Type 5 Adenovirus-Based Trypanosoma cruzi Therapeutic Vaccine Re-programs Immune Response and Reverses Chronic Cardiomyopathy |
| title_sort |
A Human Type 5 Adenovirus-Based Trypanosoma cruzi Therapeutic Vaccine Re-programs Immune Response and Reverses Chronic Cardiomyopathy |
| author |
Pereira, Isabela Resende |
| author_facet |
Pereira, Isabela Resende Pereira, Glaucia Vilar Marques, Virgínia Silva, Andrea Alice da Caetano, Bráulia Moreira, Otacilio Cruz Machado, Alexandre Vieira Romero, Oscar Bruna Rodrigues, Maurício Martins Gazzinelli, Ricardo Tostes Vieira, Joseli Lannes |
| author_role |
author |
| author2 |
Pereira, Glaucia Vilar Marques, Virgínia Silva, Andrea Alice da Caetano, Bráulia Moreira, Otacilio Cruz Machado, Alexandre Vieira Romero, Oscar Bruna Rodrigues, Maurício Martins Gazzinelli, Ricardo Tostes Vieira, Joseli Lannes |
| author2_role |
author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Pereira, Isabela Resende Pereira, Glaucia Vilar Marques, Virgínia Silva, Andrea Alice da Caetano, Bráulia Moreira, Otacilio Cruz Machado, Alexandre Vieira Romero, Oscar Bruna Rodrigues, Maurício Martins Gazzinelli, Ricardo Tostes Vieira, Joseli Lannes |
| dc.subject.en.pt_BR.fl_str_mv |
CD8-Positive T-Lymphocytes/immunology Chagas Cardiomyopathy/prevention & control Immune System Processes Vaccines, DNA/genetics |
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CD8-Positive T-Lymphocytes/immunology Chagas Cardiomyopathy/prevention & control Immune System Processes Vaccines, DNA/genetics |
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Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil |
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2015 |
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2015-12-15T13:56:01Z |
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2015-12-15T13:56:01Z |
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2015 |
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PEREIRA, Isabela Resende et al. A Human Type 5 Adenovirus-Based Trypanosoma cruzi Therapeutic Vaccine Re-programs Immune Response and Reverses Chronic Cardiomyopathy. PLoS Pathog, vol. 11, n. 1, p. e1004594, 2015. |
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https://www.arca.fiocruz.br/handle/icict/12415 |
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1553-7366 |
| dc.identifier.doi.none.fl_str_mv |
10.1371/journal.ppat.1004594 |
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PEREIRA, Isabela Resende et al. A Human Type 5 Adenovirus-Based Trypanosoma cruzi Therapeutic Vaccine Re-programs Immune Response and Reverses Chronic Cardiomyopathy. PLoS Pathog, vol. 11, n. 1, p. e1004594, 2015. 1553-7366 10.1371/journal.ppat.1004594 |
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Public Library of Science |
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Public Library of Science |
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