Skills, Knowledge, and Translational Technologies Leading to Novel Vaccines
In the distant past, several societies practiced a kind of “empirical vaccination,” but it is only recently that we are able to “rationally design” vaccines. Molecular engineering allows us to synthesize subunits of certain vaccines. Armed with novel synt
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Skills, Knowledge, and Translational Technologies Leading to Novel Vaccines The Immunological Fundamentals S¸efik S¸. Alkan
Abstract
In the distant past, several societies practiced a kind of “empirical vaccination,” but it is only recently that we are able to “rationally design” vaccines. Molecular engineering allows us to synthesize subunits of certain vaccines. Armed with novel synthetic adjuvants, and modern delivery methods, we now can potentiate the desired immune response in some vaccines. However, we have not yet discovered all the rules of induction of protective immune responses. Toward this goal, this chapter summarizes our recent understanding of the immune system as a whole. In order to protect us from microbes, the cells of the immune system need to make the right decisions, and that can only be achieved by proper “education.” Thus, cells receive their first education in the thymus school and learn how to discriminate “self from ‘nonself’.” They continue higher education in the periphery and learn how to tolerate self. During evolution, we learned to make use of two protective systems: innate and adaptive immunities. Innate immunity operates under the control of germ-line genes; thus, it is very quick and crude, lacks fine specificity, and has no memory. This system recognizes the “common” structures of microbes by means of pattern recognition molecules such as Toll-like receptors (TLR), NLRs, RIG-I, etc. On the contrary, adaptive immunity is slow, but specific, and generates memory cells. In order to recognize “uncommon” microbial structures, this system needs to generate enough diversity so that it can cope with rapidly growing, and unpredictably changing microbes. During coevolution, we survived because our adaptive immunity has learned to generate, from limited sets of germ-line genes, more diversity
S¸.S¸. Alkan (*) Department of Molecular Genetics and Microbiology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ, USA Alkan Consulting LLC, Mittlere Str. 8, CH-4056 Basel, Switzerland e-mail: [email protected] A. von Gabain and C. Klade (eds.), Development of Novel Vaccines, DOI 10.1007/978-3-7091-0709-6_1, # Springer-Verlag Wien 2012
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than microbes can ever generate. In short, self-tolerance, specificity, diversity, and memory are the hallmarks of the immune system. A well-coordinated collaboration of these rapid and slow systems is a prerequisite for the success of vaccines (and for that matter, our survival). Also, design of a vaccine depends on how much we know about the “invasion strategy” of each infectious agent. Only then can we induce appropriate B-cell (antibody) and T-cell responses (T-helper-1 (TH1), TH2, TH17, T-regulatory cells, and T-killer cells). As the immune cells integrate a multitude of signals at a given time, these T-cell subsets are induced in distinct conditions and can be reinforced or destabilized by other conditions. To this end, recent studies have used systems biology approaches to obtai
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