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Title: 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
Authors: Rigato, Paula Ordonhez [UNIFESP]
Alencar, Bruna C. de [UNIFESP]
Vasconcelos, Jose Ronnie C. de [UNIFESP]
Dominguez, Mariana R. [UNIFESP]
Araujo, Adriano F. [UNIFESP]
Machado, Alexandre V.
Gazzinelli, Ricardo T.
Bruna-Romero, Oscar
Rodrigues, Mauricio M. [UNIFESP]
Universidade Federal de São Paulo (UNIFESP)
Fiocruz MS
Universidade Federal de Minas Gerais (UFMG)
Univ Massachusetts
Issue Date: 1-May-2011
Publisher: Amer Soc Microbiology
Citation: Infection and Immunity. Washington: Amer Soc Microbiology, v. 79, n. 5, p. 2120-2130, 2011.
Abstract: Recently, 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.
ISSN: 0019-9567
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