| First Author | Rigato PO | Year | 2011 |
| Journal | Infect Immun | Volume | 79 |
| Issue | 5 | Pages | 2120-30 |
| PubMed ID | 21357719 | Mgi Jnum | J:171948 |
| Mgi Id | MGI:5002430 | Doi | 10.1128/IAI.01190-10 |
| Citation | Rigato PO, et al. (2011) 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. Infect Immun 79(5):2120-30 |
| abstractText | 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. |
