Intranasal immunization with recombinant Lactococci carrying human papillomavirus E7 protein and mouse interleukin-12 DNA induces E7-specific antitumor effects in C57BL/6 mice

Abstract

The use of Lactococcus lactis for the co-delivery of antigens and cytokines has been shown to successfully induce a special immune response. However, it is unknown whether the same results may be triggered through immunization of animals with L. lactis simultaneously carrying protein antigen and cytokine DNA. The present study evaluated the protective effects of intranasally administered live L. lactis strains carrying human papillomavirus 16 E7 protein and murine interleukin-12 (IL-12) DNA (LL-E7P-IL-12D) in a TC-1 tumor animal model. C57BL/6 mice were intranasally immunized with recombinant lactococci, and assays for cytotoxicity measurement and tumor protection were carried out to assess the immunological effects of the vaccine candidates. IL-12 and interferon-γ serum levels were measured and immunization with LL-E7P-IL-12D was shown to induce an E7-specific immune response and to confer protection against TC-1-induced tumors in vivo. Mice in the LL-E7P-IL-12D group showed an 80% survival rate when the control mice had died. Therapeutic immunization with recombinant L. lactis strains 7 days after TC-1 injection led to a reduction in the number of palpable tumors in treated mice. The antitumor effects of the vaccination occurred through an E7-specific cytotoxic T-lymphocyte response. In the present study, the use of a single L. lactis strain, to co-administer protein antigen and adjuvant DNA, successfully induced an antigen-specific immune response. These observations demonstrate a new strategy for the use of L. lactis as a delivery vector of therapeutic molecules and antigens.