Heterologous Plasmid DNA Prime-Recombinant Human Adenovirus 5 Boost Vaccination Generates a Stable Pool of Protective Long-Lived CD8(+) T Effector Memory Cells Specific for a Human Parasite, Trypanosoma cruzi

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dc.contributor.authorRigato, Paula Ordonhez [UNIFESP]
dc.contributor.authorAlencar, Bruna Cunha Gondim de [UNIFESP]
dc.contributor.authorVasconcelos, Jose Ronnie Carvalho de [UNIFESP]
dc.contributor.authorDominguez, Mariana Ribeiro [UNIFESP]
dc.contributor.authorAraujo, Adriano Fernando da Silva [UNIFESP]
dc.contributor.authorMachado, Alexandre de Magalhaes Vieira
dc.contributor.authorGazzinelli, Ricardo Tostes
dc.contributor.authorBruna-Romero, Oscar
dc.contributor.authorRodrigues, Mauricio Martins [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionFiocruz MS
dc.contributor.institutionUniversidade Federal de Minas Gerais (UFMG)
dc.contributor.institutionUniv Massachusetts
dc.date.accessioned2016-01-24T14:16:40Z
dc.date.available2016-01-24T14:16:40Z
dc.date.issued2011-05-01
dc.description.abstractRecently, we described a heterologous prime-boost strategy using plasmid DNA followed by replication-defective human recombinant adenovirus type 5 as a powerful strategy to elicit long-lived CD8(+) T-cell-mediated protective immunity against experimental systemic infection of mice with a human intracellular protozoan parasite, Trypanosoma cruzi. in the present study, we further characterized the protective long-lived CD8(+) T cells. We compared several functional and phenotypic aspects of specific CD8(+) T cells present 14 or 98 days after the last immunizing dose and found the following: (i) the numbers of specific cells were similar, as determined by multimer staining or by determining the number of gamma interferon (IFN-gamma)-secreting cells by enzyme-linked immunospot (ELISPOT) assay; (ii) these cells were equally cytotoxic in vivo; (iii) following in vitro stimulation, a slight decline in the frequency of multifunctional cells (CD107a(+) IFN-gamma(+) or CD107a(+) IFN-gamma(+) tumor necrosis factor alpha positive [TNF-alpha(+)]) was paralleled by a significant increase of CD107a singly positive cells after 98 days; (iv) the expression of several surface markers was identical, except for the reexpression of CD127 after 98 days; (v) the use of genetically deficient mice revealed a role for interleukin-12 (IL-12)/IL-23, but not IFN-gamma, in the maintenance of these memory cells; and (vi) subsequent immunizations with an unrelated virus or a plasmid vaccine or the depletion of CD4(+) T cells did not significantly erode the number or function of these CD8(+) T cells during the 15-week period. From these results, we concluded that heterologous plasmid DNA prime-adenovirus boost vaccination generated a stable pool of functional protective long-lived CD8(+) T cells with an effector memory phenotype.en
dc.description.affiliationUniversidade Federal de São Paulo, Escola Paulista Med, UNIFESP, CTCMol, BR-04044010 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, BR-04044010 São Paulo, Brazil
dc.description.affiliationFiocruz MS, Ctr Pesquisas Rene Rachou, BR-30190002 Belo Horizonte, MG, Brazil
dc.description.affiliationUniv Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, BR-31270901 Belo Horizonte, MG, Brazil
dc.description.affiliationUniv Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01655 USA
dc.description.affiliationUniv Fed Minas Gerais, Dept Microbiol, Inst Ciencias Biol, BR-31270901 Belo Horizonte, MG, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Escola Paulista Med, UNIFESP, CTCMol, BR-04044010 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, BR-04044010 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt
dc.description.sponsorshipMillennium Institute for Gene Therapy (Brazil)
dc.description.sponsorshipIDFAPESP: 2006/1983-4pt
dc.description.sponsorshipIDFAPESP: 2009/06820-4pt
dc.description.sponsorshipIDCNPq: 420067/2005-1pt
dc.format.extent2120-2130
dc.identifierhttps://dx.doi.org/10.1128/IAI.01190-10
dc.identifier.citationInfection and Immunity. Washington: Amer Soc Microbiology, v. 79, n. 5, p. 2120-2130, 2011.
dc.identifier.doi10.1128/IAI.01190-10
dc.identifier.fileWOS000289672700034.pdf
dc.identifier.issn0019-9567
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/33654
dc.identifier.wosWOS:000289672700034
dc.language.isoeng
dc.publisherAmer Soc Microbiology
dc.relation.ispartofInfection and Immunity
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleHeterologous Plasmid DNA Prime-Recombinant Human Adenovirus 5 Boost Vaccination Generates a Stable Pool of Protective Long-Lived CD8(+) T Effector Memory Cells Specific for a Human Parasite, Trypanosoma cruzien
dc.typeinfo:eu-repo/semantics/article
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