Neonatal BCG Immunization Followed by DNAhsp65 Boosters: Highly Immunogenic but not Protective Against Tuberculosis - a Paradoxical Effect of the Vector?
Autor(a) principal: | |
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Data de Publicação: | 2010 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1111/j.1365-3083.2009.02352.x http://hdl.handle.net/11449/18290 |
Resumo: | A new tuberculosis vaccine is urgently needed. Prime-boost strategies are considered very promising and the inclusion of BCG is highly desirable. In this investigation, we tested the protective efficacy of BCG delivered in the neonatal period followed by boosters in the adult phase with a DNA vaccine containing the hsp65 gene from Mycobacterium leprae (pVAXhsp65). Immune responses were characterized by serum anti-hsp65 antibody levels and IFN-gamma and IL-5 production by the spleen. Amounts of these cytokines were also determined in lung homogenates. Protective efficacy was established by the number of colony-forming units (CFU) and histopathological analysis of the lungs after challenge with Mycobacterium tuberculosis. Immunization with BCG alone triggered a significant reduction of CFU in the lungs and also clearly preserved the pulmonary parenchyma. BCG priming also increased the immunogenicity of pVAXhsp65. However, boosters with pVAXhsp65 or the empty vector abolished the protective efficacy of BCG. Also, higher IL-5 levels were produced by spleen and lungs after DNA boosters. These results demonstrated that neonatal BCG immunization followed by DNAhsp65 boosters is highly immunogenic but is not protective against tuberculosis. |
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spelling |
Neonatal BCG Immunization Followed by DNAhsp65 Boosters: Highly Immunogenic but not Protective Against Tuberculosis - a Paradoxical Effect of the Vector?A new tuberculosis vaccine is urgently needed. Prime-boost strategies are considered very promising and the inclusion of BCG is highly desirable. In this investigation, we tested the protective efficacy of BCG delivered in the neonatal period followed by boosters in the adult phase with a DNA vaccine containing the hsp65 gene from Mycobacterium leprae (pVAXhsp65). Immune responses were characterized by serum anti-hsp65 antibody levels and IFN-gamma and IL-5 production by the spleen. Amounts of these cytokines were also determined in lung homogenates. Protective efficacy was established by the number of colony-forming units (CFU) and histopathological analysis of the lungs after challenge with Mycobacterium tuberculosis. Immunization with BCG alone triggered a significant reduction of CFU in the lungs and also clearly preserved the pulmonary parenchyma. BCG priming also increased the immunogenicity of pVAXhsp65. However, boosters with pVAXhsp65 or the empty vector abolished the protective efficacy of BCG. Also, higher IL-5 levels were produced by spleen and lungs after DNA boosters. These results demonstrated that neonatal BCG immunization followed by DNAhsp65 boosters is highly immunogenic but is not protective against tuberculosis.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)São Paulo State Univ UNESP, Dept Microbiol Immunol, Biosci Inst, BR-18618000 São Paulo, BrazilSão Paulo State Univ UNESP, Dept Morphol, Biosci Inst, BR-18618000 São Paulo, BrazilUniv São Paulo, Dept Biochem & Immunol, São Paulo, BrazilSão Paulo State Univ UNESP, Dept Microbiol Immunol, Biosci Inst, BR-18618000 São Paulo, BrazilSão Paulo State Univ UNESP, Dept Morphol, Biosci Inst, BR-18618000 São Paulo, BrazilFAPESP: 03/06348-7Wiley-Blackwell Publishing, IncUniversidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)Pelizon, A. C. [UNESP]Martins, D. R. [UNESP]Zorzella-Pezavento, S. F. G. [UNESP]Seger, J. [UNESP]Justulin, L. A. [UNESP]da Fonseca, D. M.Santos, R. R.Masson, A. P.Silva, C. L.Sartori, Alexandrina [UNESP]2014-05-20T13:51:14Z2014-05-20T13:51:14Z2010-02-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article63-69application/pdfhttp://dx.doi.org/10.1111/j.1365-3083.2009.02352.xScandinavian Journal of Immunology. Malden: Wiley-blackwell Publishing, Inc, v. 71, n. 2, p. 63-69, 2010.0300-9475http://hdl.handle.net/11449/1829010.1111/j.1365-3083.2009.02352.xWOS:000273688300001WOS000273688300001.pdf4977572416129527Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengScandinavian Journal of Immunology2.3140,891info:eu-repo/semantics/openAccess2023-12-03T06:13:55Zoai:repositorio.unesp.br:11449/18290Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-12-03T06:13:55Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Neonatal BCG Immunization Followed by DNAhsp65 Boosters: Highly Immunogenic but not Protective Against Tuberculosis - a Paradoxical Effect of the Vector? |
title |
Neonatal BCG Immunization Followed by DNAhsp65 Boosters: Highly Immunogenic but not Protective Against Tuberculosis - a Paradoxical Effect of the Vector? |
spellingShingle |
Neonatal BCG Immunization Followed by DNAhsp65 Boosters: Highly Immunogenic but not Protective Against Tuberculosis - a Paradoxical Effect of the Vector? Pelizon, A. C. [UNESP] |
title_short |
Neonatal BCG Immunization Followed by DNAhsp65 Boosters: Highly Immunogenic but not Protective Against Tuberculosis - a Paradoxical Effect of the Vector? |
title_full |
Neonatal BCG Immunization Followed by DNAhsp65 Boosters: Highly Immunogenic but not Protective Against Tuberculosis - a Paradoxical Effect of the Vector? |
title_fullStr |
Neonatal BCG Immunization Followed by DNAhsp65 Boosters: Highly Immunogenic but not Protective Against Tuberculosis - a Paradoxical Effect of the Vector? |
title_full_unstemmed |
Neonatal BCG Immunization Followed by DNAhsp65 Boosters: Highly Immunogenic but not Protective Against Tuberculosis - a Paradoxical Effect of the Vector? |
title_sort |
Neonatal BCG Immunization Followed by DNAhsp65 Boosters: Highly Immunogenic but not Protective Against Tuberculosis - a Paradoxical Effect of the Vector? |
author |
Pelizon, A. C. [UNESP] |
author_facet |
Pelizon, A. C. [UNESP] Martins, D. R. [UNESP] Zorzella-Pezavento, S. F. G. [UNESP] Seger, J. [UNESP] Justulin, L. A. [UNESP] da Fonseca, D. M. Santos, R. R. Masson, A. P. Silva, C. L. Sartori, Alexandrina [UNESP] |
author_role |
author |
author2 |
Martins, D. R. [UNESP] Zorzella-Pezavento, S. F. G. [UNESP] Seger, J. [UNESP] Justulin, L. A. [UNESP] da Fonseca, D. M. Santos, R. R. Masson, A. P. Silva, C. L. Sartori, Alexandrina [UNESP] |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Universidade de São Paulo (USP) |
dc.contributor.author.fl_str_mv |
Pelizon, A. C. [UNESP] Martins, D. R. [UNESP] Zorzella-Pezavento, S. F. G. [UNESP] Seger, J. [UNESP] Justulin, L. A. [UNESP] da Fonseca, D. M. Santos, R. R. Masson, A. P. Silva, C. L. Sartori, Alexandrina [UNESP] |
description |
A new tuberculosis vaccine is urgently needed. Prime-boost strategies are considered very promising and the inclusion of BCG is highly desirable. In this investigation, we tested the protective efficacy of BCG delivered in the neonatal period followed by boosters in the adult phase with a DNA vaccine containing the hsp65 gene from Mycobacterium leprae (pVAXhsp65). Immune responses were characterized by serum anti-hsp65 antibody levels and IFN-gamma and IL-5 production by the spleen. Amounts of these cytokines were also determined in lung homogenates. Protective efficacy was established by the number of colony-forming units (CFU) and histopathological analysis of the lungs after challenge with Mycobacterium tuberculosis. Immunization with BCG alone triggered a significant reduction of CFU in the lungs and also clearly preserved the pulmonary parenchyma. BCG priming also increased the immunogenicity of pVAXhsp65. However, boosters with pVAXhsp65 or the empty vector abolished the protective efficacy of BCG. Also, higher IL-5 levels were produced by spleen and lungs after DNA boosters. These results demonstrated that neonatal BCG immunization followed by DNAhsp65 boosters is highly immunogenic but is not protective against tuberculosis. |
publishDate |
2010 |
dc.date.none.fl_str_mv |
2010-02-01 2014-05-20T13:51:14Z 2014-05-20T13:51:14Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1111/j.1365-3083.2009.02352.x Scandinavian Journal of Immunology. Malden: Wiley-blackwell Publishing, Inc, v. 71, n. 2, p. 63-69, 2010. 0300-9475 http://hdl.handle.net/11449/18290 10.1111/j.1365-3083.2009.02352.x WOS:000273688300001 WOS000273688300001.pdf 4977572416129527 |
url |
http://dx.doi.org/10.1111/j.1365-3083.2009.02352.x http://hdl.handle.net/11449/18290 |
identifier_str_mv |
Scandinavian Journal of Immunology. Malden: Wiley-blackwell Publishing, Inc, v. 71, n. 2, p. 63-69, 2010. 0300-9475 10.1111/j.1365-3083.2009.02352.x WOS:000273688300001 WOS000273688300001.pdf 4977572416129527 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Scandinavian Journal of Immunology 2.314 0,891 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
63-69 application/pdf |
dc.publisher.none.fl_str_mv |
Wiley-Blackwell Publishing, Inc |
publisher.none.fl_str_mv |
Wiley-Blackwell Publishing, Inc |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1799965156321525760 |