Principles in Immunology for the Design and Development of Vaccines.

Vaccinology has come a long way from early, empirically developed vaccines to modern vaccines rationally designed and produced. Vaccines are meant to cooperate with the human immune system, the later largely unknown in the early years of vaccine development. In the recent years, a tremendous depth of knowledge has been accumulated in the field of immunology that has provided an opportunity to understand the mechanisms of action of the vaccine components. In parallel, our knowledge in microbiology, molecular biology, infectiology, epidemiology, and furthermore in bioinformatics has fostered our understanding of the interaction of microorganisms with the human immune system. Strategies engaged by pathogens strongly determine the targets of a vaccine, which should be formulated to stimulate potent and efficiently protective immune responses. The improved knowledge of immune response mechanisms has facilitated the development of new vaccines with the capacity to selectively address the key pathogenic mechanisms. The primary goal of a vaccine design might no longer be to mimic the pathogen but to identify the relevant processes of the pathogenic mechanisms to be effectively interrupted by a highly specific immune response, eventually surpassing natural limitations. Vaccines have become complex sets of components meant to orchestrate the fine-tuning of the immune processes leading to a lasting and specific immune memory. In addition to antigenic materials, which are comprised of the most critical immunogenic epitopes, adjuvant components are frequently added to induce a favorable immunological activation. Furthermore, for reasons of production and product stability preservatives, stabilizers, inactivators, antibiotics, or diluents could be present, but need to be evaluated. While on the one hand vaccine effectiveness is a primary goal, on the other hand side effects need to be excluded due to safety and tolerability. Further challenges in vaccinology include variability of the vaccinees, the variability of the pathogen, the population-based settings of vaccine application, and the process technology in vaccine production. Vaccine design has become more tailored and in turn has opened up the potential of extending its application to hitherto not accessible complex microbial pathogens plus providing new immunotherapies to tackle diseases such as cancer, Alzheimer's disease, and autoimmune disease. This chapter gives an overview of the key considerations and processes involved in vaccine design and development. It also describes the basic principles of normal immune responses and in their function in defense of infectious agents by vaccination.