Overall recent research on TLRs has led to tremendous increase in our understanding of early steps in pathogen recognition and will presumably lead to potent TLR targeting therapeutics in the future. This book reviews and highlights our recent understanding on the function and ligands of TLRs as well as their role in autoimmunity, dendritic cell activation and target structures for therapeutic intervention.

The induction of antigen-specific immune responses after in vivo transfection with expression plasmids has triggered a revolution of vaccine research. After a first hype, evoked by the fascinating options of this method, clinical studies did not reach the ambitious aims and a phase of disillusion ensued. It became obvious that Gene vaccines displayed a weaker immunogenicity in humans than had been observed in the mouse models. Meanwhile these hurdles have been overcome and gene vaccines undergo a renaissance. The present book gives an update of the “world of naked gene vaccines”, namely DNA and RNA vaccines. Its content ranges from general mechanisms, inherent immunostimulatory properties and the vast potential to modulate immune responses, to recent successful clinical studies and approved veterinary gene vaccines. Beyond the state-of-the-art of genetic immunization, the reader will be stimulated with a chapter addressing “burning questions”.

Vaccination has been established as an efficient procedure to prevent infections. Over the past few years, a new method of subunit vaccination has attracted the attention of immunologists. Despite its popularity, it is only recently that the basic mechanisms that drive the immune response to the encoded antigen have begun to unfold. The multidisciplinary approach of this book outlines the basic characteristics of gene (DNA) vaccination, the role of APCs or bone marrow derived cells in the induction of the immune response. It points out the potential applications for various infectious and allergic diseases and describes the multifaceted properties of DNA in initiating and determining the subsequent immune responses to the encoded antigen.

Genetic / DNA immunization represents a novel approach to vaccine and immune therapeutic development. The direct injec tion of nucleic acid expression cassettes into a living host results in a limited number of its cells becoming factories for production of the introduced gene products. This host-inappropriate gene expression has important immunological consequences, resulting in the specific immune activation of the host against the gene delivered antigen. The recent demonstration by a number of laboratories that the induced immune responses are functional in experimental models against both specific infectious diseases and cancers is likely to have dramatic consequences for the develop ment of a new generation of experimental vaccines and immune therapies. This technology has the potential to enable the pro duction of vaccines and immune-based therapies that are not only effective immunologically but are accessible to the entire world (rather than just to the most developed nations). Vaccine Development Vaccination against pathogenic microorganisms represents one of the most important advances in the history of medicine. Vaccines, including those against polio, measles, mumps, rubella, hepatitis A, hepatitis B, pertussis and other diseases, have dramatically improved and protected more human lives than any other avenue of modern medicine. The vaccine against smallpox, for example, has been so successful that it is now widely believed that this malicious killer, responsible for more deaths in the twentieth century than World Wars I and II combined, has been removed from the face of the earth.

Wolf's discovery demonstrating that a reporter gene is expressed in myocytes subsequent to injection of naked DNA, was exploited by immunologists and vaccinologists to develop a new generation of vaccines. This observation galvanized the research and in a short lapse of time, an oceanic volume of knowledge has been accumulated. The research carried out in a variety of animal models showed the efficacy of genetic immunization against viruses, bacteria, and some parasites by the ability to induce a strong priming effect resulting from long-lasting persistence of plasmid as episomes. Furthermore, it was demonstrated that newborn or infant immune unresponsiveness to classical vaccines can be corrected by genetic immunization. The applications of genetic immunization for prophylaxis of infections was extended to immunotherapy, namely, cancerous, auto immune, and allergic diseases. Immunologists have provided pertinent information on the cellular basis of the immune responses elicited by genetic immunization, and molecular biologists have established the molecular basis of intrinsic adjuvant properties of plasmids.

In the early 1990s, almost 200 yr after Edward Jenner demonstrated the effectiveness of the smallpox vaccine, a new paradigm for vaccination emerged. The conventional method of vaccination required delivery of whole pathogens or structural subunits, but in this new approach, DNA or genetic information was administered to elicit an immunological response. Once it was observed that plasmid DNA delivered in vivo led to production of an encoded transgene (1), two ground-breaking studies demonstrated that immunological responses could be generated against antigenic transgenes via plasmid DNA delivered by DNA vaccination (as this approach is called) (2,3). The appe- ance of this new vaccination strategy coincided with advances in molecular biology, which provided new tools to study and manipulate the basic elements of an organism’s genome and also could also be applied to the design and production of DNA vaccines. DNA Vaccines is a major updated and enhancement of the first edition. It reviews state-of-the-art methods in DNA vaccine technology, with chapters describing DNA vaccine design, delivery systems, adjuvants, current appli- tions, methods of production, and quality control. Consistent with the approach of the Methods in Molecular Medicine series, these chapters contain detailed practical procedures on the latest DNA vaccine technology. The enthusiasm for DNA vaccine technology is made clear by the number of research studies published on this topic since the mid-1990s.

The field of biotechnology has evolved over the past four decades, developing medicines which are curing diseases. But this journey of success has been tough and arduous, built upon the shoulders of major failures. Good Genes Gone Bad highlights seven such colossal failures in drug development-all of which culminated in the development of novel drugs-weaving together various analogies through the stories and thus allowing the reader to understand complex biological phenomena. These stories include treatment of medical conditions such as genetic clotting disorder (haemophilia), childhood-diarrhoea (rotavirus vaccine), preventing HIV infection, activation of the immune systems to treat cancer, gene therapy for treatment of diseases caused by gene-defects/mutations, cell therapy for treatment of leukaemias, and finally the success of Biocon's approval of the first biologic drug for breast cancer. Written by the former R&D head of Biocon, India's largest pharmaceutical company, Good Genes Gone Bad is a fascinating look at the complex world of medicine and drug development, providing the readers with a sense of magnitude of challenges and the extent of difficulty that it takes to make novel medicines.