Co-Administration of a Plasmid DNA Encoding IL-15 Improves Long-Term Protection of a Genetic Vaccine against Trypanosoma cruzi

Co-Administration of a Plasmid DNA Encoding IL-15 Improves Long-Term Protection of a Genetic Vaccine against Trypanosoma cruzi

Author Eickhoff, Christopher S. Google Scholar
Vasconcelos, Jose R. Autor UNIFESP Google Scholar
Sullivan, Nicole L. Google Scholar
Blazevic, Azra Google Scholar
Bruna-Romero, Oscar Google Scholar
Rodrigues, Mauricio M. Autor UNIFESP Google Scholar
Hoft, Daniel F. Google Scholar
Institution St Louis Univ
Universidade Federal de São Paulo (UNIFESP)
Universidade Federal de Minas Gerais (UFMG)
Abstract Background: Immunization of mice with the Trypanosoma cruzi trans-sialidase (TS) gene using plasmid DNA, adenoviral vector, and CpG-adjuvanted protein delivery has proven highly immunogenic and provides protection against acute lethal challenge. However, long-term protection induced by TS DNA vaccines has not been reported. the goal of the present work was to test whether the co-administration of a plasmid encoding IL-15 (pIL-15) could improve the duration of protection achieved through genetic vaccination with plasmid encoding TS (pTS) alone.Methodology: We immunized BALB/c mice with pTS in the presence or absence of pIL-15 and studied immune responses [with TS-specific IFN-gamma ELISPOT, serum IgG ELISAs, intracellular cytokine staining (IFN-gamma, TNF-alpha, and IL-2), tetramer staining, and CFSE dilution assays] and protection against lethal systemic challenge at 1 to 6 months post vaccination. Mice receiving pTS alone developed robust TS-specific IFN-gamma responses and survived a lethal challenge given within the first 3 months following immunization. the addition of pIL-15 to pTS vaccination did not significantly alter T cell responses or protection during this early post-vaccination period. However, mice vaccinated with both pTS and pIL-15 challenged 6 months post-vaccination were significantly more protected against lethal T. cruzi challenges than mice vaccinated with pTS alone (P<0.05). Improved protection correlated with significantly higher numbers of TS-specific IFN-gamma producing total and CD8(+) T cells detected >6 months post immunization. Also, these TS-specific T cells were better able to expand after in vitro restimulation.Conclusion: Addition of pIL-15 during genetic vaccination greatly improved long-term T cell survival, memory T cell expansion, and long-term protection against the important human parasite, T. cruzi.
Language English
Sponsor National Institutes of Health
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Millennium Institute for Gene Therapy
Grant number National Institutes of Health: RO1 AI040196
CNPq: 420067/2005-1
Date 2011-03-01
Published in Plos Neglected Tropical Diseases. San Francisco: Public Library Science, v. 5, n. 3, 13 p., 2011.
ISSN 1935-2727 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent 13
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000288940800017

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