title: 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 ofLactococcus lactisfor 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 withL. lactissimultaneously carrying protein antigen and cytokine DNA. The present study evaluated the protective effects of intranasally administered liveL. lactisstrains 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-12Dwas shown to induce an E7-specific immune response and to confer protection against TC-1-induced tumorsin vivo. Mice in the LL-E7P-IL-12D group showed an 80% survival rate when the control mice had died. Therapeutic immunization with recombinantL. lactisstrains 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 singleL. lactisstrain, to co-administer protein antigen and adjuvant DNA, successfully induced an antigen-specific immune response. These observations demonstrate a new strategy for the use ofL. lactisas a delivery vector of therapeutic molecules and antigens.
authors.affiliation: Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang 830046, P.R. China.
authors.forename: Yijie
authors.initials: Y
authors.lastname: Li
authors.affiliation: Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang 830046, P.R. China.
authors.forename: Xinping
authors.initials: X
authors.lastname: Li
authors.affiliation: Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang 830046, P.R. China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang 830046, P.R. China.
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Zhuang
authors.affiliation: Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang 830046, P.R. China ; Department of Pediatrics, Texas Children's Cancer Center, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yang
authors.affiliation: Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang 830046, P.R. China.
authors.forename: Fuchun
authors.initials: F
authors.lastname: Zhang
keywords: Lactococcus lactis; antitumor; co-delivery; human papillomavirus; intranasal immunization