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Full Description
Antigens encoded by DNA vaccines can induce all arms of the adaptive immune response, but to date they have proven most effective at inducing antigen-specific CD8+ T cells. The great majority of experiments have been carried out in small animal models, where these vac cines work quite well; in a limited number of studies in primates (including humans), their effectiveness, although demonstrable, is somewhat diminished. Therefore, to accelerate the introduction of DNA vaccines into clinical and veterinary practice, it is important that their immunogenicity be enhanced. The rational modification of DNA vaccines requires that we have a basic understanding of the mechanisms which underpin successful DNA immuniza tion. In this chapter, we review how DNA vaccines may work, and how this information per mits us to exploit biological pathways to improve the outcome of genetic immunization. In addition to reviewing "rational" vaccine modification (based on, e. g. , targeting antigens to specific antigen presentation pathways; or co-administering cytokines to modulate the vaccine-induced response) we also consider "empirical" approaches, such as using different prime-boost regimens which-by a mechanism as yet unclear-appear to greatly enhance antigen-specific memory in the vaccinee. Empirical studies proved the efficacy of essentially all vaccines in current use, and this old approach may once again prove useful in launching a new technology into the clinical arena. References 1. Whitton JL. Lymphocytic choriomeningitis virus CTL. Sem Virol 1990; 1:257-262. 2. Good RA. and Zak SJ. Disturbance in gamma-globulin synthesis as "experiments of nature".
Contents
1. Overview of Vaccinology in Historic and Future Perspective: The Whence and Whither of a Dynamic Science with Complex Dimensions.- 2. Dendritic Cells: Important Adjuvants During DNA Vaccination.- 3. Activation of the Innate Immune System by DNA Vaccines.- 4. Induction of B Cells by DNA Vaccines.- 5. Immune Responses to DNA Vaccines: Induction of CD8+ T Cells.- 6. Minigene-Based Vaccines for Eliciting CD8+ T Cell Responses.- 7. DNA Vaccines Against RNA Viruses.- 8. DNA Vaccines Against Herpesviruses.- 9. Genetic Immunization Against HIV.- 10. DNA Vaccines Against Bacterial Pathogens.- 11. DNA Vaccines as Cancer Treatment Modalities.- 12. DNA Vaccines for Allergic Diseases.- 13. Immune Responses in Gene Transfer for Genetic Disorders.- 14. The Use of DNA Vaccines for Neonatal/Early Life Childhood Immunization.- 15. DNA Delivery with Attenuated Intracellular Bacteria.- 16. Cytokines and Immunomodulatory Ligands as Genetic Adjuvants.- 17. Chemokines: Role as Immunomodulators and Potential as Adjuvants for DNA Vaccines.- 18. DNA Vaccines: Safety and Regulatory Issues.- 19. The Introduction of New DNA Vaccines into Developing Countries.
