Coadministration of an Interleukin-12 Gene and a<i>Trypanosoma cruzi</i>Gene Improves Vaccine Efficacy

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  • Masaharu Katae
    Department of Respiratory Medicine
  • Yasushi Miyahira
    Department of Molecular and Cellular Parasitology
  • Kazuyoshi Takeda
    Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421
  • Hironori Matsuda
    Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421
  • Hideo Yagita
    Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421
  • Ko Okumura
    Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421
  • Tsutomu Takeuchi
    Department of Tropical Medicine and Parasitology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582
  • Tsuneo Kamiyama
    Department of Veterinary Sciences, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
  • Akihiko Ohwada
    Department of Respiratory Medicine
  • Yoshinosuke Fukuchi
    Department of Respiratory Medicine
  • Takashi Aoki
    Department of Molecular and Cellular Parasitology

Abstract

<jats:title>ABSTRACT</jats:title><jats:p>We tested the immunogenicity of two<jats:italic>Trypanosoma cruzi</jats:italic>antigens injected into mice in the form of DNA vaccine. Immunization with DNA encoding dihydroorotate dehydrogenase did not confer protective immunity in all mouse strains tested. Immunization with DNA encoding trans-sialidase surface antigen (TSSA) protected C57BL/6 (<jats:italic>H-2<jats:sup>b</jats:sup></jats:italic>) mice but not BALB/c (<jats:italic>H-2<jats:sup>d</jats:sup></jats:italic>) or C3H/Hej (<jats:italic>H-2<jats:sup>k</jats:sup></jats:italic>) mice against lethal<jats:italic>T. cruzi</jats:italic>infection. In vivo depletion of CD4<jats:sup>+</jats:sup>or CD8<jats:sup>+</jats:sup>T cells abolished the protective immunity elicited by TSSA gene in C57BL/6 mice. Enzyme-linked immunospot assay with splenocytes from<jats:italic>T. cruzi</jats:italic>-infected mice or TSSA gene-vaccinated mice identified an<jats:italic>H-2K<jats:sup>b</jats:sup></jats:italic>-restricted antigenic peptide, ANYNFTLV. The CD8<jats:sup>+</jats:sup>-T-cell line specific for this peptide could recognize<jats:italic>T. cruzi</jats:italic>-infected cells in vitro and could protect naive mice from lethal infection when adoptively transferred. Coadministration of the interleukin-12 (IL-12) gene with the TSSA gene facilitated the induction of ANYNFTLV-specific CD8<jats:sup>+</jats:sup>T cells and improved the vaccine efficacy against lethal<jats:italic>T. cruzi</jats:italic>infection. These results reinforced the utility of immunomodulatory adjuvants such as IL-12 gene for eliciting protective immunity against intracellular parasites by DNA vaccination.</jats:p>

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