CRC NEW GEN VACC PDF

Preface to the Third Edition

In the intervening years since the publication of the second edition of New Generation Vaccines, extraordinary advances have occurred in the field of vaccines and immunization. These encompass not only breakthroughs in research and development but also advances in assuring vaccine safety, standardizing the way clinical trials are performed (and how data are monitored and validated), manufacture of vaccines, and the public health use of vaccines. The third edition of New Generation Vaccines highlights these and many other relevant changes in the field of vaccinology and puts them in a historical perspective.

At the time of publication of the last edition, clinical trials with DNA vaccines were just beginning and there was great expectation that this technology might revolutionize vaccinology. The results of these clinical trials, now available, reveal that DNA vaccines used alone do not meet expectations. On the other hand, fundamental improvements in DNA vaccines and the advent of "heterologous prime-boost" strategies have rekindled interest in their use in focused ways. DNA vaccines appear able to prime subjects so that they can respond to the same antigens when presented in another formulation as a boosting regimen, for example, by means of a viral live vector.

Since the last edition, the Bill and Melinda Gates Foundation has completely revolutionized the funding of research and development and the performance of clinical trials of candidate vaccines against neglected diseases, such as malaria, AIDS, tuberculosis, leishmaniasis, Dengue fever, Group A Neisseria menigitidis, and shigellosis.

Another seminal event since the publication of the second edition has been the formation of the Global Alliance for Vaccines and Immunization (GAVI) and its financial instrument, the Vaccine Fund. Working in unison through GAVI, major global partners in immunization (e.g., the World Health Organization, UNICEF, the World Bank, the Gates Foundation, etc.) are raising immunization coverage and introducing new vaccines to infants residing in the world's 74 poorest countries. A chapter in this edition describes GAVI and the Vaccine Fund, including their research objectives.

Since the last edition, two new conjugate vaccines have been licensed, including a seven-valent pneumococcal conjugate that is now used widely in the United States and a Group C meningococcal conjugate that is used extensively in the United Kingdom. Programmatic use of these vaccines has had a profound impact in diminishing the respective disease burdens.

Since the last edition was published, a major dichotomy has appeared between the industrialized world and developing countries with respect to the vaccines administered to infants and children, their site of manufacture, the formulations and combinations of vaccine antigens, and immunization schedules. A vibrant vaccine industry is emerging in developing countries (e.g., India, Indonesia, Brazil, Cuba) that now supplies most of the vaccine utilized in developing countries; these vaccines are becoming increasingly distinct from those used in industrialized countries. Vaccine safety is increasingly becoming a focus of public concern in industrialized countries, where many pediatric infectious diseases (e.g., diphtheria, measles, pertussis) have largely disappeared and populations do not feel threatened by these infections. In industrialized countries, the switch from live oral polio vaccine to inactivated polio vaccine, the introduction of less reactogenic acellular pertussis vaccine, the discontinuation of use of thimerosal as a preservative in multidose vials, and the withdrawal of a live rotavirus vaccine after it was incriminated as a rare cause of intussusception within one week following immunization of infants are all examples of this trend as regulatory and public health actions are taken to enhance vaccine safety. These topics are all covered in a series of chapters on regulatory issues and vaccine safety. In contrast, in developing countries where infections such as measles, pertussis, and diphtheria still pose notable risks of severe disease and death, and financial resources are constrained, the emphasis is to achieve the highest coverage possible with the most potent vaccines, even at the cost of some reactogenicity.

Another trend in industrialized countries is the search for vaccines to prevent or treat ("vaccine therapy") various chronic infections that afflict these populations and create an enormous economic burden. Accordingly, chapters that describe strategies to develop vaccines against Alzheimer's disease, rheumatoid arthritis, insulin-dependent diabetes, multiple sclerosis, and various forms of cancer are included in this edition.

The science of immunology continues to blaze new trails for vaccinology, and multiple chapters in this edition review this work. Practical ways of immunizing without the use of needles are also covered, including mucosal immunization, transcutaneous immunization, and the use of needle-free injection devices.

The tragedy of September 11, 2001, when terrorists hijacked airliners and flew them into the World Trade Center towers in New York City resulting in thousands of deaths, and the bioterrorist dissemination of anthrax spores through the postal system that followed shortly thereafter and resulted in two dozen cases and six deaths (and in major disruption of civil society) had a perceptible impact on vaccinology. Following these events, governments in the United States and many other countries encouraged the development of new or improved vaccines against several potential bioterror agents and diverted resources toward that end. Chapters covering this subject are also found in this edition.

The pace and extent of modern vaccine development make it impossible to include within a single volume all the notable research advances on all vaccines. Accordingly, as before, there are gaps. For example, progress on the development of vaccines to prevent Pseudomonas aeruginosa pulmonary disease in cystic fibrosis patients is omitted, as are updates on progress in administering attenuated measles vaccine by aerosol and the development of new measles vaccines that aim to immunize infants in the developing world who are too young to get the current parenteral vaccine.

Assembling the third edition of New Generation Vaccines has been a formidable undertaking that required input and help from many individuals. We heartily thank all the authors who contributed the diverse chapters that comprise the fundamental strength of the volume. We also express our indebtedness to Sandra Beberman and Barbara Mathieu of Marcel Dekker, Inc., who provided invaluable assistance and guidance. Special thanks and appreciation go to our families and friends who gave encouragement and showed patience during the many evening and weekend hours consumed in the preparation and editing of the book. Finally, this volume could not have been completed without the organizational prowess, fastidious attention to detail, tenacity, technical competence, and diplomatic skills of Mrs. Dottie Small, Assistant to Myron M. Levine.