The SFC values for individual mice (open circles) and geometric means (solid diamonds) are shown. intramuscular injection of Bac-CEA. Interestingly, the Bac-G-E2 vector was shown to be a more efficient immunogen than Bac-E2, in view of HIV-1 integrase inhibitor the 10-fold difference in the minimal dose required to elicit a measurable T-cell response upon intramuscular injection. Induction of inflammatory cytokines such as gamma interferon, tumor necrosis factor alpha, and interleukin-6 was detected as early as 6 h postinjection of Bac-G-E2. Most importantly, both vectors elicited CD8+ T cells with effector function capable of lysing target cells loaded with a hepatitis C virus-specific epitope. Additionally, enhanced NK cytolytic activity was detected in immunized mice. Thus, these results further demonstrate that baculovirus may be considered a useful vector for gene therapy. Recent advances in immunology and molecular biology have stimulated the development of gene-based vaccines. These vaccines are designed to generate both cellular and humoral responses that can be used to prevent infectious diseases and to treat cancer, allergies, and autoimmune diseases (38). Two general classes of gene-based vaccines are being developed. The first HIV-1 integrase inhibitor is based on the use of plasmid DNA encoding the target antigen. However, the use of plasmid DNA as a gene transfer vehicle for immunization is somewhat limited by the low transduction efficiency that hampers its immunogenic potential. To overcome this problem, numerous strategies are being developed that use electrical stimulation, microparticles, adjuvants, and costimulatory molecules to enhance both the gene transfer capabilities and the intrinsic immunogenicity of plasmid DNA (24). Viruses have highly evolved structures that enable them to bind to cells and deliver genes into the cells that they infect. Thus, it is reasonable to consider using live virus vaccines to induce cytolytic T lymphocytes to treat a disease in which cellular immunity is an absolute requirement. To this end, a variety of viral vectors, primarily based on poxvirus and adenovirus, have been tested, with encouraging results (21, 36). However, these vectors are themselves antigenic and can cause inflammation, which, Rabbit Polyclonal to WIPF1 depending on the site of injection and on the recipient’s state of health, may constitute a liability for their use as vehicles for vaccination. An additional drawback is that existing immunity due to previous infection (as in the case of adenovirus) or to vaccination (smallpox) may limit the potency of the vaccine by clearing the viral vector before it can infect cells and deliver its payload of antigen genes (8, 13). Thus, there is a need to identify unrelated viral vectors that function efficiently as gene transfer vehicles for immunization whose efficacy is not limited by problems connected with toxicity or existing immunity. In recent years, baculovirus has emerged as a vector with great potential for gene transfer in mammalian cells (31). Baculoviruses are a group of insect viruses possessing a rod-shaped capsid in which is packaged a condensed DNA genome, a double-stranded, covalently closed circular molecule ranging between 80 and 200 kbp in length (30). The baculovirus multiple nucleopolyhedrovirus has long been used as a biopesticide and as a tool for efficient recombinant protein production in insect cells (26, 28). Although its host specificity was originally thought to be restricted to HIV-1 integrase inhibitor cells derived from arthropods, baculovirus was shown to infect a number of mammalian cells and animal models (2, 6, 10, 12, 18, 23, 32, 33, 34, 37, 39, 40, 42). Gene transfer mediated by baculovirus carrying the reporter gene under the control of a strong mammalian promoter such as the immediate-early promoter of cytomegalovirus (CMV) or the chimeric CMV early enhancer (CAG) promoter was demonstrated in a number of human primary cell lines and liver tissue (6, 42)..
