Avaliação do adjuvante Advax na formulação de vacina de subunidade proteica contra Mycobacterium tuberculosis
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFG |
Texto Completo: | http://repositorio.bc.ufg.br/tede/handle/tede/6964 |
Resumo: | Tuberculosis is an infectious disease caused mainly by the bacteria Mycobacterium tuberculosis. The only way to prevent is to vaccinate with BCG, an attenuated Mycobacterium bovis strain. However, the vaccine has variable efficacy in different people and it does not protect adults. The aim of this study was to develop new subunit vaccine formulations, evaluating a new adjuvant: Advax and two recombinant fusion proteins: CMX and ECMX. To formulate the subunit vaccines three adjuvants were used: the Advax3, Advax4 and CpG-DNA. First we addressed the CMX protein. BALB/c mice were separated in experimental groups that received 3 doses of the vaccines, besides the control groups (Saline, BCG, CMX, Advax3 and Advax4). The vaccines induced increase the local inflammatory response and they were able to activate blood and lymphatic endothelial cells on draining lymph nodes. After the first dose, the mice vaccinated with Advax3 + CMX, Advax4 + CMX and CpG-DNA + CMX generate IgG2a humoral immune response. After the second dose, the vaccinated mice also induced an IgG1 response. After challenging with M. tuberculosis and after 45 days, the vaccines BCG, Advax3 + CMX, Advax4 + CMX and CpG-DNA + CMX showed specific Th1 responses. However, the Th17 cellular response was not observed. Evaluating the lung lesions induced by the infection, Advax4 + CMX group presented reduced inflammatory cell infiltrate and maintenance on the pulmonary architecture. The vaccines Advax3 + CMX e Advax4 + CMX were able to extend the animals life, but none, except the BCG, were able to reduce the bacillary load on the lungs of infected mice, forty five or ninety days after the challenge. To improve the vaccine, ECMX was tested with Advax4. This vaccine showed similar humoral and cellular responses and reduced M. tuberculosis bacillary load. The vaccine formulations developed were immunogenic and the formulations containing Advax4 + ECMX were more effective and may be tested as vaccine against tuberculosis. |
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Junqueira-Kipnis, Ana Paulahttp://lattes.cnpq.br/1252262903952987Kipnis, Andréhttp://lattes.cnpq.br/4434965360286741Junqueira-Kipnis, Ana PaulaPfrimer, Irmtraut Araci HoffmannSilva, Juliana Reis Machado ehttp://lattes.cnpq.br/2984214120372542Santos, Bruno de Paula Oliveira2017-03-20T13:52:55Z2017-03-10SANTOS, B. P. O. Avaliação do adjuvante Advax na formulação de vacina de subunidade proteica contra Mycobacterium tuberculosis. 2017.112 f. Dissertação (Mestrado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2017.http://repositorio.bc.ufg.br/tede/handle/tede/6964ark:/38995/00130000019w0Tuberculosis is an infectious disease caused mainly by the bacteria Mycobacterium tuberculosis. The only way to prevent is to vaccinate with BCG, an attenuated Mycobacterium bovis strain. However, the vaccine has variable efficacy in different people and it does not protect adults. The aim of this study was to develop new subunit vaccine formulations, evaluating a new adjuvant: Advax and two recombinant fusion proteins: CMX and ECMX. To formulate the subunit vaccines three adjuvants were used: the Advax3, Advax4 and CpG-DNA. First we addressed the CMX protein. BALB/c mice were separated in experimental groups that received 3 doses of the vaccines, besides the control groups (Saline, BCG, CMX, Advax3 and Advax4). The vaccines induced increase the local inflammatory response and they were able to activate blood and lymphatic endothelial cells on draining lymph nodes. After the first dose, the mice vaccinated with Advax3 + CMX, Advax4 + CMX and CpG-DNA + CMX generate IgG2a humoral immune response. After the second dose, the vaccinated mice also induced an IgG1 response. After challenging with M. tuberculosis and after 45 days, the vaccines BCG, Advax3 + CMX, Advax4 + CMX and CpG-DNA + CMX showed specific Th1 responses. However, the Th17 cellular response was not observed. Evaluating the lung lesions induced by the infection, Advax4 + CMX group presented reduced inflammatory cell infiltrate and maintenance on the pulmonary architecture. The vaccines Advax3 + CMX e Advax4 + CMX were able to extend the animals life, but none, except the BCG, were able to reduce the bacillary load on the lungs of infected mice, forty five or ninety days after the challenge. To improve the vaccine, ECMX was tested with Advax4. This vaccine showed similar humoral and cellular responses and reduced M. tuberculosis bacillary load. The vaccine formulations developed were immunogenic and the formulations containing Advax4 + ECMX were more effective and may be tested as vaccine against tuberculosis.Tuberculose é uma doença infecto-contagiosa causada principalmente pelo Mycobacterium tuberculosis. A única forma de prevenção é a vacina BCG. Entretanto, essa vacina tem eficácia variável em diferentes populações e não protege indivíduos adultos. O objetivo desse trabalho foi desenvolver novas formulações vacinais de subunidade proteica testando um novo adjuvante: Advax e duas proteínas de fusão recombinante: CMX e ECMX. Foram utilizados três adjuvantes: Advax3, Advax4 e CpG-DNA. Primeiro foram testadas formulações vacinais contendo CMX. Camundongos BALB/c foram separados em grupos que receberam 3 doses de vacinas de subunidade proteica, além dos grupos controles (Salina, BCG, CMX, Advax3 e Advax4). Foram avaliadas as lesões induzidas no local da inoculação e os linfonodos drenantes. As vacinas estimularam aumento da celularidade no local da inoculação e conseguiram ativar células endoteliais vasculares e linfáticas nos linfonodos drenantes. Após a primeira dose, os camundongos vacinados com Advax3 + CMX, Advax4 + CMX e CpG-DNA + CMX geraram resposta imune humoral do tipo IgG2a. Após a segunda dose, os camundongos vacinados com as formulações citadas também induziram resposta do tipo IgG1. As vacinas BCG, Advax3 + CMX, Advax4 + CMX e CpG-DNA + CMX induziram respostas do tipo Th1 específicas tanto no baço quanto no pulmão. Entretanto, a resposta celular do tipo Th17 não foi observada. Nos cortes histológicos, foi possível observar que a formulação Advax4+CMX conseguiu reduzir o infiltrado inflamatório e manter a arquitetura tecidual. As formulações Advax3 + CMX e Advax4 + CMX conseguiram prolongar a sobrevida dos animais, mas nenhuma das vacinas, exceto a BCG, conseguiu reduzir a carga bacilar nos pulmões dos camundongos infectados. Utilizando Advax4 + ECMX observou-se o mesmo tipo de resposta imune celular e humoral que culminou com redução da carga bacilar do Mycobacterium tuberculosis. As formulações vacinais desenvolvidas são imunogênicas e a formulação vacinal contendo Advax4 + ECMX apresentou melhor eficácia e poderá ser testada como um candidato a vacina contra tuberculose.Submitted by Erika Demachki (erikademachki@gmail.com) on 2017-03-17T20:34:28Z No. of bitstreams: 2 Dissertação - Bruno de Paula Oliveira Santos - 2017.pdf: 5505330 bytes, checksum: 269d17015f2059d9a94e4f080ef0448e (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-03-20T13:52:55Z (GMT) No. of bitstreams: 2 Dissertação - Bruno de Paula Oliveira Santos - 2017.pdf: 5505330 bytes, checksum: 269d17015f2059d9a94e4f080ef0448e (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2017-03-20T13:52:55Z (GMT). No. of bitstreams: 2 Dissertação - Bruno de Paula Oliveira Santos - 2017.pdf: 5505330 bytes, checksum: 269d17015f2059d9a94e4f080ef0448e (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-03-10Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqapplication/pdfporUniversidade Federal de GoiásPrograma de Pós-graduação em Medicina Tropical e Saúde Publica (IPTSP)UFGBrasilInstituto de Patologia Tropical e Saúde Pública - IPTSP (RG)http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessVacinaTuberculoseAdvaxVaccineTuberculosisAdvaxCIENCIAS BIOLOGICAS::IMUNOLOGIAAvaliação do adjuvante Advax na formulação de vacina de subunidade proteica contra Mycobacterium tuberculosisEvaluation of Advax adjuvant in the subunit vaccine formulation against Mycobacterium tuberculosisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis6085308344741430434600600600600-77690114445645562885989919188376747614-2555911436985713659reponame:Repositório Institucional da UFGinstname:Universidade Federal de Goiás (UFG)instacron:UFGLICENSElicense.txtlicense.txttext/plain; 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dc.title.por.fl_str_mv |
Avaliação do adjuvante Advax na formulação de vacina de subunidade proteica contra Mycobacterium tuberculosis |
dc.title.alternative.eng.fl_str_mv |
Evaluation of Advax adjuvant in the subunit vaccine formulation against Mycobacterium tuberculosis |
title |
Avaliação do adjuvante Advax na formulação de vacina de subunidade proteica contra Mycobacterium tuberculosis |
spellingShingle |
Avaliação do adjuvante Advax na formulação de vacina de subunidade proteica contra Mycobacterium tuberculosis Santos, Bruno de Paula Oliveira Vacina Tuberculose Advax Vaccine Tuberculosis Advax CIENCIAS BIOLOGICAS::IMUNOLOGIA |
title_short |
Avaliação do adjuvante Advax na formulação de vacina de subunidade proteica contra Mycobacterium tuberculosis |
title_full |
Avaliação do adjuvante Advax na formulação de vacina de subunidade proteica contra Mycobacterium tuberculosis |
title_fullStr |
Avaliação do adjuvante Advax na formulação de vacina de subunidade proteica contra Mycobacterium tuberculosis |
title_full_unstemmed |
Avaliação do adjuvante Advax na formulação de vacina de subunidade proteica contra Mycobacterium tuberculosis |
title_sort |
Avaliação do adjuvante Advax na formulação de vacina de subunidade proteica contra Mycobacterium tuberculosis |
author |
Santos, Bruno de Paula Oliveira |
author_facet |
Santos, Bruno de Paula Oliveira |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Junqueira-Kipnis, Ana Paula |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/1252262903952987 |
dc.contributor.advisor-co1.fl_str_mv |
Kipnis, André |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/4434965360286741 |
dc.contributor.referee1.fl_str_mv |
Junqueira-Kipnis, Ana Paula |
dc.contributor.referee2.fl_str_mv |
Pfrimer, Irmtraut Araci Hoffmann |
dc.contributor.referee3.fl_str_mv |
Silva, Juliana Reis Machado e |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/2984214120372542 |
dc.contributor.author.fl_str_mv |
Santos, Bruno de Paula Oliveira |
contributor_str_mv |
Junqueira-Kipnis, Ana Paula Kipnis, André Junqueira-Kipnis, Ana Paula Pfrimer, Irmtraut Araci Hoffmann Silva, Juliana Reis Machado e |
dc.subject.por.fl_str_mv |
Vacina Tuberculose Advax |
topic |
Vacina Tuberculose Advax Vaccine Tuberculosis Advax CIENCIAS BIOLOGICAS::IMUNOLOGIA |
dc.subject.eng.fl_str_mv |
Vaccine Tuberculosis Advax |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS::IMUNOLOGIA |
description |
Tuberculosis is an infectious disease caused mainly by the bacteria Mycobacterium tuberculosis. The only way to prevent is to vaccinate with BCG, an attenuated Mycobacterium bovis strain. However, the vaccine has variable efficacy in different people and it does not protect adults. The aim of this study was to develop new subunit vaccine formulations, evaluating a new adjuvant: Advax and two recombinant fusion proteins: CMX and ECMX. To formulate the subunit vaccines three adjuvants were used: the Advax3, Advax4 and CpG-DNA. First we addressed the CMX protein. BALB/c mice were separated in experimental groups that received 3 doses of the vaccines, besides the control groups (Saline, BCG, CMX, Advax3 and Advax4). The vaccines induced increase the local inflammatory response and they were able to activate blood and lymphatic endothelial cells on draining lymph nodes. After the first dose, the mice vaccinated with Advax3 + CMX, Advax4 + CMX and CpG-DNA + CMX generate IgG2a humoral immune response. After the second dose, the vaccinated mice also induced an IgG1 response. After challenging with M. tuberculosis and after 45 days, the vaccines BCG, Advax3 + CMX, Advax4 + CMX and CpG-DNA + CMX showed specific Th1 responses. However, the Th17 cellular response was not observed. Evaluating the lung lesions induced by the infection, Advax4 + CMX group presented reduced inflammatory cell infiltrate and maintenance on the pulmonary architecture. The vaccines Advax3 + CMX e Advax4 + CMX were able to extend the animals life, but none, except the BCG, were able to reduce the bacillary load on the lungs of infected mice, forty five or ninety days after the challenge. To improve the vaccine, ECMX was tested with Advax4. This vaccine showed similar humoral and cellular responses and reduced M. tuberculosis bacillary load. The vaccine formulations developed were immunogenic and the formulations containing Advax4 + ECMX were more effective and may be tested as vaccine against tuberculosis. |
publishDate |
2017 |
dc.date.accessioned.fl_str_mv |
2017-03-20T13:52:55Z |
dc.date.issued.fl_str_mv |
2017-03-10 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
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masterThesis |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
SANTOS, B. P. O. Avaliação do adjuvante Advax na formulação de vacina de subunidade proteica contra Mycobacterium tuberculosis. 2017.112 f. Dissertação (Mestrado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2017. |
dc.identifier.uri.fl_str_mv |
http://repositorio.bc.ufg.br/tede/handle/tede/6964 |
dc.identifier.dark.fl_str_mv |
ark:/38995/00130000019w0 |
identifier_str_mv |
SANTOS, B. P. O. Avaliação do adjuvante Advax na formulação de vacina de subunidade proteica contra Mycobacterium tuberculosis. 2017.112 f. Dissertação (Mestrado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2017. ark:/38995/00130000019w0 |
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http://repositorio.bc.ufg.br/tede/handle/tede/6964 |
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http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
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Universidade Federal de Goiás |
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UFG |
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Brasil |
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Instituto de Patologia Tropical e Saúde Pública - IPTSP (RG) |
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Universidade Federal de Goiás |
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