Genetic vaccine for tuberculosis (pVAXhsp65) primes neonate mice for a strong immune response at the adult stage
Autor(a) principal: | |
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Data de Publicação: | 2007 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1186/1479-0556-5-12 http://hdl.handle.net/11449/69999 |
Resumo: | Background: Vaccination of neonates is generally difficult due to the immaturity of the immune system and consequent higher susceptibility to tolerance induction. Genetic immunization has been described as an alternative to trigger a stronger immune response in neonates, including significant Th1 polarization. In this investigation we analysed the potential use of a genetic vaccine containing the heat shock protein (hsp65) from Mycobacterium leprae (pVAXhsp65) against tuberculosis (TB) in neonate mice. Aspects as antigen production, genomic integration and immunogenicity were evaluated. Methods: Hsp65 message and genomic integration were evaluated by RT-PCR and Southern blot, respectively. Immunogenicity of pVAXhsp65 alone or combined with BCG was analysed by specific induction of antibodies and cytokines, both quantified by ELISA. Results: This DNA vaccine was transcribed by muscular cells of neonate mice without integration into the cellular genome. Even though this vaccine was not strongly immunogenic when entirely administered (three doses) during early animal's life, it was not tolerogenic. In addition, pVAXhsp65 and BCG were equally able to prime newborn mice for a strong and mixed immune response (Th1 + Th2) to pVAXhsp65 boosters administered later, at the adult life. Conclusion: These results suggest that pVAXhsp65 can be safely used as a priming stimulus in neonate animals in prime-boost similar strategies to control TB. However, priming with BCG or pVAXhsp65, directed the ensuing immune response triggered by an heterologous or homologous booster, to a mixed Th1/Th2 pattern of response. Measures as introduction of IL-12 or GM-CSF genes in the vaccine construct or even IL-4 neutralization, are probably required to increase the priming towards Th1 polarization to ensure control of tuberculosis infection. © 2007 Pelizon et al; licensee BioMed Central Ltd. |
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Genetic vaccine for tuberculosis (pVAXhsp65) primes neonate mice for a strong immune response at the adult stagebacterial proteinBCG vaccinegentamicinglutaminegranulocyte macrophage colony stimulating factorheat shock protein 65interleukin 12interleukin 4interleukin 5monoclonal antibodyanimal cellanimal experimentantibody productionBCG vaccinationcontrolled studycytokine productionDNA immunizationdrug safetyenzyme linked immunosorbent assaygene inductiongenetic immunizationimmune responseimmunogenicityimmunomodulationmouseMycobacterium lepraenewbornnonhumanreverse transcription polymerase chain reactionSouthern blottingTh1 cellTh2 celltuberculosis controlAnimaliaMusBackground: Vaccination of neonates is generally difficult due to the immaturity of the immune system and consequent higher susceptibility to tolerance induction. Genetic immunization has been described as an alternative to trigger a stronger immune response in neonates, including significant Th1 polarization. In this investigation we analysed the potential use of a genetic vaccine containing the heat shock protein (hsp65) from Mycobacterium leprae (pVAXhsp65) against tuberculosis (TB) in neonate mice. Aspects as antigen production, genomic integration and immunogenicity were evaluated. Methods: Hsp65 message and genomic integration were evaluated by RT-PCR and Southern blot, respectively. Immunogenicity of pVAXhsp65 alone or combined with BCG was analysed by specific induction of antibodies and cytokines, both quantified by ELISA. Results: This DNA vaccine was transcribed by muscular cells of neonate mice without integration into the cellular genome. Even though this vaccine was not strongly immunogenic when entirely administered (three doses) during early animal's life, it was not tolerogenic. In addition, pVAXhsp65 and BCG were equally able to prime newborn mice for a strong and mixed immune response (Th1 + Th2) to pVAXhsp65 boosters administered later, at the adult life. Conclusion: These results suggest that pVAXhsp65 can be safely used as a priming stimulus in neonate animals in prime-boost similar strategies to control TB. However, priming with BCG or pVAXhsp65, directed the ensuing immune response triggered by an heterologous or homologous booster, to a mixed Th1/Th2 pattern of response. Measures as introduction of IL-12 or GM-CSF genes in the vaccine construct or even IL-4 neutralization, are probably required to increase the priming towards Th1 polarization to ensure control of tuberculosis infection. © 2007 Pelizon et al; licensee BioMed Central Ltd.Department of Microbiology and Immunology Biosciences Institute São Paulo State University (UNESP), Botucatu, São Paulo 18618-000Department of Morphology Biosciences Institute São Paulo State University (UNESP), Botucatu, São Paulo 18618-000Department of Biochemistry and Immunology University of São Paulo (USP), Ribeirão Preto, São Paulo 14049-900Department of Microbiology and Immunology Biosciences Institute São Paulo State University (UNESP), Botucatu, São Paulo 18618-000Department of Morphology Biosciences Institute São Paulo State University (UNESP), Botucatu, São Paulo 18618-000Universidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)Pelizon, Ana [UNESP]Sartori, Alexandrina [UNESP]Martins, Douglas R. [UNESP]Zorzella, Sofia F.G. [UNESP]Trombone, Ana PaulaLorenzi, Júlio C.C.Carvalho, Robson F. [UNESP]Brandão, Izaíra T.Coelho-Castelo, Arlete A.M.Silva, Célio L.2014-05-27T11:22:39Z2014-05-27T11:22:39Z2007-11-29info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1186/1479-0556-5-12Genetic Vaccines and Therapy, v. 5.1479-0556http://hdl.handle.net/11449/6999910.1186/1479-0556-5-122-s2.0-389491931972-s2.0-38949193197.pdf49775724161295270000-0002-4901-7714Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengGenetic Vaccines and Therapyinfo:eu-repo/semantics/openAccess2023-12-30T06:15:33Zoai:repositorio.unesp.br:11449/69999Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T21:39:30.449108Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Genetic vaccine for tuberculosis (pVAXhsp65) primes neonate mice for a strong immune response at the adult stage |
title |
Genetic vaccine for tuberculosis (pVAXhsp65) primes neonate mice for a strong immune response at the adult stage |
spellingShingle |
Genetic vaccine for tuberculosis (pVAXhsp65) primes neonate mice for a strong immune response at the adult stage Pelizon, Ana [UNESP] bacterial protein BCG vaccine gentamicin glutamine granulocyte macrophage colony stimulating factor heat shock protein 65 interleukin 12 interleukin 4 interleukin 5 monoclonal antibody animal cell animal experiment antibody production BCG vaccination controlled study cytokine production DNA immunization drug safety enzyme linked immunosorbent assay gene induction genetic immunization immune response immunogenicity immunomodulation mouse Mycobacterium leprae newborn nonhuman reverse transcription polymerase chain reaction Southern blotting Th1 cell Th2 cell tuberculosis control Animalia Mus |
title_short |
Genetic vaccine for tuberculosis (pVAXhsp65) primes neonate mice for a strong immune response at the adult stage |
title_full |
Genetic vaccine for tuberculosis (pVAXhsp65) primes neonate mice for a strong immune response at the adult stage |
title_fullStr |
Genetic vaccine for tuberculosis (pVAXhsp65) primes neonate mice for a strong immune response at the adult stage |
title_full_unstemmed |
Genetic vaccine for tuberculosis (pVAXhsp65) primes neonate mice for a strong immune response at the adult stage |
title_sort |
Genetic vaccine for tuberculosis (pVAXhsp65) primes neonate mice for a strong immune response at the adult stage |
author |
Pelizon, Ana [UNESP] |
author_facet |
Pelizon, Ana [UNESP] Sartori, Alexandrina [UNESP] Martins, Douglas R. [UNESP] Zorzella, Sofia F.G. [UNESP] Trombone, Ana Paula Lorenzi, Júlio C.C. Carvalho, Robson F. [UNESP] Brandão, Izaíra T. Coelho-Castelo, Arlete A.M. Silva, Célio L. |
author_role |
author |
author2 |
Sartori, Alexandrina [UNESP] Martins, Douglas R. [UNESP] Zorzella, Sofia F.G. [UNESP] Trombone, Ana Paula Lorenzi, Júlio C.C. Carvalho, Robson F. [UNESP] Brandão, Izaíra T. Coelho-Castelo, Arlete A.M. Silva, Célio L. |
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, Ana [UNESP] Sartori, Alexandrina [UNESP] Martins, Douglas R. [UNESP] Zorzella, Sofia F.G. [UNESP] Trombone, Ana Paula Lorenzi, Júlio C.C. Carvalho, Robson F. [UNESP] Brandão, Izaíra T. Coelho-Castelo, Arlete A.M. Silva, Célio L. |
dc.subject.por.fl_str_mv |
bacterial protein BCG vaccine gentamicin glutamine granulocyte macrophage colony stimulating factor heat shock protein 65 interleukin 12 interleukin 4 interleukin 5 monoclonal antibody animal cell animal experiment antibody production BCG vaccination controlled study cytokine production DNA immunization drug safety enzyme linked immunosorbent assay gene induction genetic immunization immune response immunogenicity immunomodulation mouse Mycobacterium leprae newborn nonhuman reverse transcription polymerase chain reaction Southern blotting Th1 cell Th2 cell tuberculosis control Animalia Mus |
topic |
bacterial protein BCG vaccine gentamicin glutamine granulocyte macrophage colony stimulating factor heat shock protein 65 interleukin 12 interleukin 4 interleukin 5 monoclonal antibody animal cell animal experiment antibody production BCG vaccination controlled study cytokine production DNA immunization drug safety enzyme linked immunosorbent assay gene induction genetic immunization immune response immunogenicity immunomodulation mouse Mycobacterium leprae newborn nonhuman reverse transcription polymerase chain reaction Southern blotting Th1 cell Th2 cell tuberculosis control Animalia Mus |
description |
Background: Vaccination of neonates is generally difficult due to the immaturity of the immune system and consequent higher susceptibility to tolerance induction. Genetic immunization has been described as an alternative to trigger a stronger immune response in neonates, including significant Th1 polarization. In this investigation we analysed the potential use of a genetic vaccine containing the heat shock protein (hsp65) from Mycobacterium leprae (pVAXhsp65) against tuberculosis (TB) in neonate mice. Aspects as antigen production, genomic integration and immunogenicity were evaluated. Methods: Hsp65 message and genomic integration were evaluated by RT-PCR and Southern blot, respectively. Immunogenicity of pVAXhsp65 alone or combined with BCG was analysed by specific induction of antibodies and cytokines, both quantified by ELISA. Results: This DNA vaccine was transcribed by muscular cells of neonate mice without integration into the cellular genome. Even though this vaccine was not strongly immunogenic when entirely administered (three doses) during early animal's life, it was not tolerogenic. In addition, pVAXhsp65 and BCG were equally able to prime newborn mice for a strong and mixed immune response (Th1 + Th2) to pVAXhsp65 boosters administered later, at the adult life. Conclusion: These results suggest that pVAXhsp65 can be safely used as a priming stimulus in neonate animals in prime-boost similar strategies to control TB. However, priming with BCG or pVAXhsp65, directed the ensuing immune response triggered by an heterologous or homologous booster, to a mixed Th1/Th2 pattern of response. Measures as introduction of IL-12 or GM-CSF genes in the vaccine construct or even IL-4 neutralization, are probably required to increase the priming towards Th1 polarization to ensure control of tuberculosis infection. © 2007 Pelizon et al; licensee BioMed Central Ltd. |
publishDate |
2007 |
dc.date.none.fl_str_mv |
2007-11-29 2014-05-27T11:22:39Z 2014-05-27T11:22:39Z |
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/10.1186/1479-0556-5-12 Genetic Vaccines and Therapy, v. 5. 1479-0556 http://hdl.handle.net/11449/69999 10.1186/1479-0556-5-12 2-s2.0-38949193197 2-s2.0-38949193197.pdf 4977572416129527 0000-0002-4901-7714 |
url |
http://dx.doi.org/10.1186/1479-0556-5-12 http://hdl.handle.net/11449/69999 |
identifier_str_mv |
Genetic Vaccines and Therapy, v. 5. 1479-0556 10.1186/1479-0556-5-12 2-s2.0-38949193197 2-s2.0-38949193197.pdf 4977572416129527 0000-0002-4901-7714 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Genetic Vaccines and Therapy |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
Scopus 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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1808129344666599424 |