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

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dc.contributor.authorEickhoff, Christopher S.
dc.contributor.authorVasconcelos, Jose Ronnie Carvalho de [UNIFESP]
dc.contributor.authorSullivan, Nicole L.
dc.contributor.authorBlazevic, Azra
dc.contributor.authorBruna-Romero, Oscar
dc.contributor.authorRodrigues, Mauricio Martins [UNIFESP]
dc.contributor.authorHoft, Daniel F.
dc.contributor.institutionSt Louis Univ
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniversidade Federal de Minas Gerais (UFMG)
dc.date.accessioned2016-01-24T14:06:14Z
dc.date.available2016-01-24T14:06:14Z
dc.date.issued2011-03-01
dc.description.abstractBackground: 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.en
dc.description.affiliationSt Louis Univ, Dept Internal Med, St Louis, MO 63103 USA
dc.description.affiliationUniversidade Federal de São Paulo, Ctr Terapia Celular & Mol, Escola Paulista Med, São Paulo, Brazil
dc.description.affiliationSt Louis Univ, Dept Mol Microbiol, St Louis, MO 63103 USA
dc.description.affiliationUniv Fed Minas Gerais, Inst Ciencias Biol, Dept Microbiol, Belo Horizonte, MG, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Ctr Terapia Celular & Mol, Escola Paulista Med, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipNational Institutes of Health
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt
dc.description.sponsorshipMillennium Institute for Gene Therapy
dc.description.sponsorshipIDNational Institutes of Health: RO1 AI040196
dc.description.sponsorshipIDCNPq: 420067/2005-1pt
dc.format.extent13
dc.identifierhttps://dx.doi.org/10.1371/journal.pntd.0000983
dc.identifier.citationPlos Neglected Tropical Diseases. San Francisco: Public Library Science, v. 5, n. 3, 13 p., 2011.
dc.identifier.doi10.1371/journal.pntd.0000983
dc.identifier.fileWOS000288940800017.pdf
dc.identifier.issn1935-2727
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/33495
dc.identifier.wosWOS:000288940800017
dc.language.isoeng
dc.publisherPublic Library Science
dc.relation.ispartofPlos Neglected Tropical Diseases
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleCo-Administration of a Plasmid DNA Encoding IL-15 Improves Long-Term Protection of a Genetic Vaccine against Trypanosoma cruzien
dc.typeinfo:eu-repo/semantics/article
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