Imiquimod and S-27609 as adjuvants of DNA vaccination in a transgenic murine model of HER2/neu-positive mammary carcinoma

A. Smorlesi, F. Papalini, F. Orlando, A. Donnini, F. Re, M. Provinciali

Research output: Contribution to journalArticle

Abstract

DNA vaccination against HER-2/neu is an effective way to induce an immune response able to oppose the spontaneous development of mammary tumours occurring in HER-2/neu transgenic mice. In this study, we have evaluated the potential of Imiquimod and the analogue S-27609 as adjuvants of DNA vaccination against HER-2/neu in transgenic mice. The association of a DNA vaccine encoding a portion of rat HER2/neu with either Imiquimod or S-27609 was found to delay the development of spontaneous mammary tumours and to reduce their incidence, in comparison with DNA vaccination alone. Almost 80 or 40%; of tumour-free mice were found at the end of measurement time in mice vaccinated and supplemented with Imiquimod or S-27609, respectively. The antitumour preventive effect was associated with increased antibody and cell-mediated immune responsiveness against HER-2/neu. In mice vaccinated and supplemented with Imiquimod, a small but significant increase of rat p185 neu-specific cytotoxicity and of IFN-γ and IL-2-producing CD8T cells, together with a reduction of IL-4-producing CD4T cells, and a switch from an IgG1 towards a IgG2a phenotype of anti-p185 neu antibodies, suggested a TH1 polarization of the immune response. The immunoregulatory efficacy of S-27609 was lower than that observed for Imiquimod. These data highlight the potential of Imiquimod, and, to a lower extent, of S-27609, as immunological adjuvants of therapeutic DNA vaccines.

Original languageEnglish
Pages (from-to)1324-1332
Number of pages9
JournalGene Therapy
Volume12
Issue number17
DOIs
Publication statusPublished - Sep 2005

Keywords

  • Adjuvants
  • DNA vaccination
  • HER-2/neu
  • Imiquimod
  • Toll-like receptors
  • Transgenic mice

ASJC Scopus subject areas

  • Genetics

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