Genetic vaccine for tuberculosis (pVAXhsp65) primes neonate mice for a strong immune response at the adult stage

Detalhes bibliográficos
Autor(a) principal: Pelizon, Ana [UNESP]
Data de Publicação: 2007
Outros Autores: 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.
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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spelling 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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