Construção de uma vacina de subunidade proteica de mycobacterium tuberculosis e avaliação da imunogenicidade e antigenicidade
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| Data de Publicação: | 2013 |
| Tipo de documento: | Tese |
| Idioma: | por |
| Título da fonte: | Repositório Institucional da UFG |
| Texto Completo: | http://repositorio.bc.ufg.br/tede/handle/tede/3130 |
Resumo: | Tuberculosis is a re-emerging infectious disease that remains a major public health problem worldwide. Although there is the BCG vaccine that is effective against severe forms of childhood TB, in adults its efficacy is variable (0-85%). In this context there is a need to develop new vaccines to control the spread of TB. This thesis proposes the development of a new recombinant fusion M. tuberculosis protein (Ag85C-MPT51-HspX) by molecular cloning, expression in E. coli with a histidine tag and purified by ion exchange chromatography. The fusion protein was constructed successfully, expressed in E. coli BL21 and purified. Tests in mice were performed to evaluate the immunogenicity of the recombinant fusion protein Ag85C-MPT51-HspX of M. tuberculosis. Mice were immunized three times with the protein Ag85C-MPT51-HspX formulated with CpG-DNA encapsulated in liposomes, CpG-DNA encapsulated in liposomes, liposome or saline as negative control and the humoral and cellular immune response was evaluated. The immunization with the vaccine formulation induced the production of high titers of specific anti-fusion protein Ag85C-MPT51-HspX IgG1 = 3.08 ± 0.04; IgG2a = 3.10 ± 0.03) and, favored the increase of specific CD4+ IFN-γ (2.14% ± 0.17), CD4+ TNF-α (2.16 ± 0.34%). The recognizing of this protein by seric IgG and IgM discriminated patients with active TB infection from healthy individuals. We conclude that CMX protein has potential to be used for the development of vaccine against M. tuberculosis as well also for TB diagnostic kits. |
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Junqueira-Kipnis, Ana Paulahttp://lattes.cnpq.br/1252262903952987Araújo Filho, João Alves deKipnis, AndréJunqueira-Kipnis, Ana PaulaAndré, Maria Cláudia Dantas Porfírio BorgesBocca, Anamelia LorenzenttiPalaci, MoisésFonseca, Simone Gonçalves dahttp://lattes.cnpq.br/4448263553675550Sousa, Eduardo Martins de2014-09-23T15:17:05Z2013-03-27SOUSA, Eduardo Martins de. Construção de uma vacina de subunidade proteica de mycobacterium tuberculosis e avaliação da imunogenicidade e antigenicidade. 2013. 98 f. Tese (Doutorado em Medicina Tropical e Saúde Pública) - Universidade Federal de Goiás, Goiânia, 2013.http://repositorio.bc.ufg.br/tede/handle/tede/3130Tuberculosis is a re-emerging infectious disease that remains a major public health problem worldwide. Although there is the BCG vaccine that is effective against severe forms of childhood TB, in adults its efficacy is variable (0-85%). In this context there is a need to develop new vaccines to control the spread of TB. This thesis proposes the development of a new recombinant fusion M. tuberculosis protein (Ag85C-MPT51-HspX) by molecular cloning, expression in E. coli with a histidine tag and purified by ion exchange chromatography. The fusion protein was constructed successfully, expressed in E. coli BL21 and purified. Tests in mice were performed to evaluate the immunogenicity of the recombinant fusion protein Ag85C-MPT51-HspX of M. tuberculosis. Mice were immunized three times with the protein Ag85C-MPT51-HspX formulated with CpG-DNA encapsulated in liposomes, CpG-DNA encapsulated in liposomes, liposome or saline as negative control and the humoral and cellular immune response was evaluated. The immunization with the vaccine formulation induced the production of high titers of specific anti-fusion protein Ag85C-MPT51-HspX IgG1 = 3.08 ± 0.04; IgG2a = 3.10 ± 0.03) and, favored the increase of specific CD4+ IFN-γ (2.14% ± 0.17), CD4+ TNF-α (2.16 ± 0.34%). The recognizing of this protein by seric IgG and IgM discriminated patients with active TB infection from healthy individuals. We conclude that CMX protein has potential to be used for the development of vaccine against M. tuberculosis as well also for TB diagnostic kits.A tuberculose é uma doença infecciosa re-emergente que permanece como um dos maiores problemas de saúde pública mundial. Embora exista a vacina BCG que é eficiente contra formas graves de TB na infância, em adultos a eficácia é variável (0 a 85%). Nesse contexto existe a necessidade do desenvolvimento de novas vacinas para controlar a disseminação da TB. O presente trabalho teve como objetivo desenvolver uma nova proteína de fusão recombinante (Ag85C-MPT51-HspX) de M. tuberculosis a partir da clonagem molecular, expressão em E. coli com uma cauda de histidina e purificação através de cromatografia de troca iônica. A proteína de fusão foi construída com sucesso expressa em E. coli BL21 e purificada. Ensaios em camundongos foram realizados para avaliar a imunogenicidade da proteína recombinante de fusão Ag85C-MPT51-HspX de M. tuberculosis. Os camundongos foram imunizados três vezes com a proteína Ag85C-MPT51-HspX formulada com CpG-DNA encapsulada em lipossoma, CpG-DNA encapsulado em lipossoma, lipossoma ou salina como controle negativo e a resposta imune humoral e celular foi avaliada . A imunização com a formulação vacinal induziu a produção de altos títulos de anticorpos específicos anti-proteína de fusão Ag85C-MPT51-HspX (IgG1 =3,08±0,04; IgG2a=3,10±0,03), bem como, favoreceu o aumento de células T CD4+IFN-γ (2,14%±0,17), CD4+TNF-α (2,16%±0,34) específicas. A avaliação do reconhecimento desta proteína de fusão tanto por IgM quanto IgG humana sérica permitiu discriminar pacientes com tuberculose ativa de controles saudáveis, demonstrando a antigenicidade desta molécula em humanos. Conclui-se que a proteína CMX poderá ser testada tanto como vacina, assim como para o desenvolvimento de testes de diagnóstico para a tuberculose.Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2014-09-23T13:40:05Z No. of bitstreams: 2 Sousa, Eduardo Martins.pdf: 2216793 bytes, checksum: b28a546dbb9489fa820abe22bc2b6109 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2014-09-23T15:17:05Z (GMT) No. of bitstreams: 2 Sousa, Eduardo Martins.pdf: 2216793 bytes, checksum: b28a546dbb9489fa820abe22bc2b6109 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Made available in DSpace on 2014-09-23T15:17:05Z (GMT). No. of bitstreams: 2 Sousa, Eduardo Martins.pdf: 2216793 bytes, checksum: b28a546dbb9489fa820abe22bc2b6109 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2013-03-27Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqapplication/pdfhttp://repositorio.bc.ufg.br/tede/retrieve/8367/Sousa%2c%20Eduardo%20Martins.pdf.jpgporUniversidade Federal de GoiásPrograma de Pós-graduação em Medicina Tropical e Saúde Publica (IPTSP)UFGBrasilInstituto de Patologia Tropical e Saúde Pública - IPTSP (RG)1. ABOU-ZEID C, ROOK G, MINNIKIN DE, PARLETT JH, OSBORN TW & GRANGE JM. 1987. Effect of the method of preparation of bacillus Calmette-Guérin (BCG) vaccine on the properties of four daughter strains. Journal of Applied Bacteriology. 63: 449-453. 2. ACHKAR JM, DONG Y, HOLZMAN RS, BELISLE J, KOURBETI IS, SHERPA T, CONDOS R, ROM WN AND LAAL S. 2006. 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SIMPSON, Y. Q. ZHU, M. J. HICKEY, D. R. SHERMAN, and C. E. BARRY III. 1998. The 16-kDa alpha-crystallin (Acr) protein of Mycobacterium tuberculosis is required for growth in macrophages. Proc. Natl. Acad. Sci. USA 95:9578-9583. 152. ZHANG M, GATELY MK, WANG E, GONG J, WOLF SF, LU S, MODLIN RL, BARNES PF 1994. Interleukin 12 at the site of disease in tuberculosis. 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| dc.title.por.fl_str_mv |
Construção de uma vacina de subunidade proteica de mycobacterium tuberculosis e avaliação da imunogenicidade e antigenicidade |
| dc.title.alternative.eng.fl_str_mv |
Construction of a protein subunit vaccine mycobacterium tuberculosis and evaluation of immunogenicity and antigenicity |
| title |
Construção de uma vacina de subunidade proteica de mycobacterium tuberculosis e avaliação da imunogenicidade e antigenicidade |
| spellingShingle |
Construção de uma vacina de subunidade proteica de mycobacterium tuberculosis e avaliação da imunogenicidade e antigenicidade Sousa, Eduardo Martins de Tuberculose Vacina de subunidade Proteína recombinante Tuberculosis Subunit vaccine Recombinant protein SAUDE COLETIVA::MEDICINA PREVENTIVA |
| title_short |
Construção de uma vacina de subunidade proteica de mycobacterium tuberculosis e avaliação da imunogenicidade e antigenicidade |
| title_full |
Construção de uma vacina de subunidade proteica de mycobacterium tuberculosis e avaliação da imunogenicidade e antigenicidade |
| title_fullStr |
Construção de uma vacina de subunidade proteica de mycobacterium tuberculosis e avaliação da imunogenicidade e antigenicidade |
| title_full_unstemmed |
Construção de uma vacina de subunidade proteica de mycobacterium tuberculosis e avaliação da imunogenicidade e antigenicidade |
| title_sort |
Construção de uma vacina de subunidade proteica de mycobacterium tuberculosis e avaliação da imunogenicidade e antigenicidade |
| author |
Sousa, Eduardo Martins de |
| author_facet |
Sousa, Eduardo Martins de |
| 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 |
Araújo Filho, João Alves de |
| dc.contributor.advisor-co2.fl_str_mv |
Kipnis, André |
| dc.contributor.referee1.fl_str_mv |
Junqueira-Kipnis, Ana Paula |
| dc.contributor.referee2.fl_str_mv |
André, Maria Cláudia Dantas Porfírio Borges |
| dc.contributor.referee3.fl_str_mv |
Bocca, Anamelia Lorenzentti |
| dc.contributor.referee4.fl_str_mv |
Palaci, Moisés |
| dc.contributor.referee5.fl_str_mv |
Fonseca, Simone Gonçalves da |
| dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/4448263553675550 |
| dc.contributor.author.fl_str_mv |
Sousa, Eduardo Martins de |
| contributor_str_mv |
Junqueira-Kipnis, Ana Paula Araújo Filho, João Alves de Kipnis, André Junqueira-Kipnis, Ana Paula André, Maria Cláudia Dantas Porfírio Borges Bocca, Anamelia Lorenzentti Palaci, Moisés Fonseca, Simone Gonçalves da |
| dc.subject.por.fl_str_mv |
Tuberculose Vacina de subunidade Proteína recombinante |
| topic |
Tuberculose Vacina de subunidade Proteína recombinante Tuberculosis Subunit vaccine Recombinant protein SAUDE COLETIVA::MEDICINA PREVENTIVA |
| dc.subject.eng.fl_str_mv |
Tuberculosis Subunit vaccine Recombinant protein |
| dc.subject.cnpq.fl_str_mv |
SAUDE COLETIVA::MEDICINA PREVENTIVA |
| description |
Tuberculosis is a re-emerging infectious disease that remains a major public health problem worldwide. Although there is the BCG vaccine that is effective against severe forms of childhood TB, in adults its efficacy is variable (0-85%). In this context there is a need to develop new vaccines to control the spread of TB. This thesis proposes the development of a new recombinant fusion M. tuberculosis protein (Ag85C-MPT51-HspX) by molecular cloning, expression in E. coli with a histidine tag and purified by ion exchange chromatography. The fusion protein was constructed successfully, expressed in E. coli BL21 and purified. Tests in mice were performed to evaluate the immunogenicity of the recombinant fusion protein Ag85C-MPT51-HspX of M. tuberculosis. Mice were immunized three times with the protein Ag85C-MPT51-HspX formulated with CpG-DNA encapsulated in liposomes, CpG-DNA encapsulated in liposomes, liposome or saline as negative control and the humoral and cellular immune response was evaluated. The immunization with the vaccine formulation induced the production of high titers of specific anti-fusion protein Ag85C-MPT51-HspX IgG1 = 3.08 ± 0.04; IgG2a = 3.10 ± 0.03) and, favored the increase of specific CD4+ IFN-γ (2.14% ± 0.17), CD4+ TNF-α (2.16 ± 0.34%). The recognizing of this protein by seric IgG and IgM discriminated patients with active TB infection from healthy individuals. We conclude that CMX protein has potential to be used for the development of vaccine against M. tuberculosis as well also for TB diagnostic kits. |
| publishDate |
2013 |
| dc.date.issued.fl_str_mv |
2013-03-27 |
| dc.date.accessioned.fl_str_mv |
2014-09-23T15:17:05Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
| format |
doctoralThesis |
| status_str |
publishedVersion |
| dc.identifier.citation.fl_str_mv |
SOUSA, Eduardo Martins de. Construção de uma vacina de subunidade proteica de mycobacterium tuberculosis e avaliação da imunogenicidade e antigenicidade. 2013. 98 f. Tese (Doutorado em Medicina Tropical e Saúde Pública) - Universidade Federal de Goiás, Goiânia, 2013. |
| dc.identifier.uri.fl_str_mv |
http://repositorio.bc.ufg.br/tede/handle/tede/3130 |
| identifier_str_mv |
SOUSA, Eduardo Martins de. Construção de uma vacina de subunidade proteica de mycobacterium tuberculosis e avaliação da imunogenicidade e antigenicidade. 2013. 98 f. Tese (Doutorado em Medicina Tropical e Saúde Pública) - Universidade Federal de Goiás, Goiânia, 2013. |
| url |
http://repositorio.bc.ufg.br/tede/handle/tede/3130 |
| dc.language.iso.fl_str_mv |
por |
| language |
por |
| dc.relation.program.fl_str_mv |
6085308344741430434 |
| dc.relation.confidence.fl_str_mv |
600 600 600 600 |
| dc.relation.department.fl_str_mv |
-7769011444564556288 |
| dc.relation.cnpq.fl_str_mv |
-317746863433440698 |
| dc.relation.sponsorship.fl_str_mv |
-2555911436985713659 |
| dc.relation.references.por.fl_str_mv |
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