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

dc.creatorRigato, Paula Ordonhez
dc.creatorBargieri, Bruna Cunha de Alencar
dc.creatorVasconcelos, Jose Ronnie Carvalho de
dc.creatorDominguez, Mariana Ribeiro
dc.creatorAraujo, Adriano Fernando
dc.creatorMachado, Alexandre Vieira
dc.creatorGazzinelli, Ricardo Tostes
dc.creatorRomero, Oscar Bruna
dc.creatorRodrigues, Mauricio Martins
dc.date2014-12-02T13:27:20Z
dc.date2014-12-02T13:27:20Z
dc.date2011
dc.date.accessioned2023-09-27T00:12:13Z
dc.date.available2023-09-27T00:12:13Z
dc.identifier0019-9567
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/9029
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8898482
dc.descriptionRecently, 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-cellmediated 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-)-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- or CD107a IFN- tumor necrosis factor alpha positive [TNF-]) 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-, 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherAmerican Society for Microbiology
dc.rightsopen access
dc.subjectheterologous
dc.subjectTrypanosoma cruzi
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 cruzi
dc.typeArticle


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