| Multicellular organisms must face the myriad potentially pathogenic microorganisms. This evolutionary pressure from the challenge of the microbial world has shaped the complex immune system that provide a flexible and dynamic mechanism to respond specifically to a wide variety of antigens. The mechanisms by which the immune system controls disease include the induction of neutralizing antibodies specific for the antigenic determinants of the immunogen, as well as the expansion and differentiation of antigen-specific regulatory and effector T-lymphocytes. Antibodies provide protection by preventing the virus infection, recruiting bactericidal mechanisms and neutralizing bacterial toxins. T helper (Th) cells also contribute to resistance against bacterial and viral diseases by producing bioactive molecules that cause inflammation and stimulate macrophage and CD8+ T cell responses. However, antibody and Th cell responses do not eliminate most tumor or virally infected cells. In these situations, cytotoxic T lymphocyte (CTL) is the main specific effector, which mediates the disorder cell clearance through perforin-dependent cytolysis or elaboration of Fas ligand. Unfortunately, most conventional vaccines fail to elicit CTL response, and this has been a major limitation in the development of immunotherapies against viral diseases and cancer.To activate CTL response, a number of vaccine strategies are being pursued. According to the method of antigen presentation, these CD8+ T cell vaccines can be categorized into two broad groups. One method is toproduce modified cells that include the hybrid cell vaccine, antigen-loaded dendritic cells (DCs), or somatic cell expressing costimulatory molecules. These vaccines maybe directly induce CTL responses without professional APC presentation and have demonstrated encouraging data, especially peptide-loaded DCs. However, this kind of vaccines requires ex vivo culturing the cells and reinfusion back into recipients. It is a laborious, patient-restricted, and expensive process. The alternative method to develop effective CD8+ T vaccines is to construct exogenous antigen vaccines such as live attenuated virus or bacteria, chimeric virus particles, particle protein, liposome or ISCOMs, peptide, and naked DNA. These vaccines must be presented by professional APC in vivo to elicit CTL responses. Although these strategies are still early in development, 1000-10000 fold higher antigen presentation efficiency in the class I pathway has been observed if the exogenous antigens are attached to small particles.The filamentous phage viron is an asymmetric particle about 6nm in diameter and 800-2000nm long. Since the first report presented by George P Smith in 1985, phage display system has been used extensively to express large diverse foreign antigen. Recently , it also has been shown that filamentous phage is an effective antigen delivery system to induce high titer antibody respones. In this research, the ability of inducing MHC class I restricted cytotoxic T lymphocyte response in vivo via recombinant filamentous phage was firstly investigated. To achieve this aim, the DNA fragment encoded HBs28-39 oligopeptide was insert into phagemid vector pC89. The correct transformant was superinfected with VASM13 helper phage to produce the hybrid filamentous phage particle. After the immunization of recombinant particles into BALB/c (H-2d) mice, a MHC class I restricted HBs specific CTL response was observed.Furthermore, the efficacy of this new antigen delivery system in inducing protective and therapeutic anti-tumor immune responses was studied. We genetically fused the tumor rejection antigen P1 A epitope to the N-terminus of the major coat protein pVIII of filamentous phage. After subcutaneous injection of phage display particles a protective immune response against a lethal progressive P815 mastocytoma tumor cell challenge was established. Moreover, the vaccine suppressed growth of preexisting tumors. Immunization with the hybrid phage particles elicited P1A35-43 speci...
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