BIOTECHNOLOGY - V. H. Herasymenko - 2006

Part II. Specialized Biotechnologies

Chapter 16. DNA VACCINES

16.4. MODULATION OF THE IMMUNE RESPONSE

Blood sera of intact animals contain low titers of anti-DNA autoantibodies, but they exhibit low Specificity. DNA molecules are weak immunogens due to their flexible conformation in solution; therefore, the administration of recombinant Plasmids into animal Tissues does not significantly affect anti-DNA antibody titers.

For many Antigens, inoculation of 50–100 µg of purified plasmid DNA, with or without booster administration, elicits a robust Immune Response against the corresponding protein encoded by the DNA vaccine. Numerous studies in laboratory animals have demonstrated that The amount of recombinant plasmid required for DNA vaccination can range from 0.001 to 10 µg per gram of body weight, which largely depends on the chosen administration method and site. For instance, in some cases, intradermal delivery of a DNA vaccine yields an immune response equal to or greater than that achieved via intramuscular injection, while utilizing plasmid DNA concentrations hundreds of times lower. This can be attributed to the fact that the Skin and mucous membranes serve as the primary anatomical portals for most exogenous antigens. Skin-associated lymphoid tissues harbor specialized Cells that enhance the immune response. Keratinocytes produce interleukin-1 (IL-1) and tumor necrosis factor-alpha, which activate lymphocytes, macrophages, and dendritic cells. Skin Langerhans cells transport antigens from the skin to the Lymph Nodes (Fig. 16.2). They act as potential activators of naive T lymphocytes. A specialized subset of circulating T lymphocytes (epidermotropic lymphocytes) migrates to the skin and plays a critical role in cutaneous Immunity. Dermal dendritic cells and macrophages can also capture antigens and initiate an immune response. Thus, In Vivo Gene gun transfection of epidermal or dermal cells with DNA can be considered an effective route of genetic immunization, mimicking the physiological response to a pathogen during an infection or when using live Vaccines. At the same time, evidence exists (Deruabin et al., 2003) that without applying mechanical force to drive DNA directly into cells, intramuscular immunization is quite effective, yielding the highest level of antigen expression. A distinctive feature of this route is the induction of Cell-mediated immunity characterized by the generation of predominantly specific cytotoxic T lymphocytes (CTLs), whereas the exact mechanism underlying the HUMORAL IMMUNE RESPONSE remains incompletely understood due to the scarce population of antigen-presenting cells in Muscle tissue.

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Fig. 16.2. Schematic diagram of immune response modulation following intradermal DNA vaccine administration

The Development of an immune response following DNA vaccination possesses certain distinct features. Using tick-borne encephalitis virus as an example, it was demonstrated that despite the very low level of viral Gene Expression during genetic immunization—amounting to 10^-12 g—an immune response was successfully induced, providing effective protection for the animals. In contrast, immunization with dissolved inactivated protein vaccines at a viral protein concentration of approximately 10^-9 g failed to elicit antibody titers detectable even by enzyme-linked immunosorbent assay (Morozova et al., 2000). Consequently, DNA vaccine administration triggers both specific cell-mediated and humoral immune responses.