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

Author(s)

Rigato, Paula Ordonhez ^[1] ; de Alencar, Bruna C. ^[1] ; de Vasconcelos, Jose Ronnie C. ^[1] ; Dominguez, Mariana R. ^[1] ; Araujo, Adriano F. ^[1] ; Machado, Alexandre V. ^[2] ; Gazzinelli, Ricardo T. ^{[2, 3, 4]} ; Bruna-Romero, Oscar ^[5] ; Rodrigues, Mauricio M. ^{[1, 6]}

Affiliation

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, BR-04044010 Sao Paulo - Brazil

^[2] Fiocruz MS, Ctr Pesquisas Rene Rachou, BR-30190002 Belo Horizonte, MG - Brazil

^[3] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, BR-31270901 Belo Horizonte, MG - Brazil

^[4] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01655 - USA

^[5] Univ Fed Minas Gerais, Dept Microbiol, Inst Ciencias Biol, BR-31270901 Belo Horizonte, MG - Brazil

^[6] Univ Fed Sao Paulo, Escola Paulista Med, UNIFESP, CTCMol, BR-04044010 Sao Paulo - Brazil

• Document type: Journal article
• Source: Infection and Immunity; v. 79, n. 5, p. 2120-2130, MAY 2011.
• Web of Science Citations: 32

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. (AU)

• FAPESP's process: 09/06820-4 - Characterization of antigen presenting cells capable of initiating the immune response and control the immunodominance during Trypanosoma cruzi infection
• Grantee: Maurício Martins Rodrigues
• Support Opportunities: Regular Research Grants