New Generation Vaccines PDF

Preface

Vaccinology continues, impressively, to advance and mature both in the development of new and improved vaccines and in the implementation of vaccines to prevent disease, thus requiring the publication of the new fourth edition. Some technologies highlighted with great expectation in the previous edition have progressed admirably in clinical trials, whereas others have proved disappointing and have been abandoned altogether.

Some of the important changes that have taken place in the field and are featured in this edition include several new vaccines that have been recently licensed, including a quadrivalent (groups A, C, W135, and Y) meningococcal conjugate vaccine, two oral rotavirus vaccines, and two human papillomavirus (HPV) vaccines based on virus-like particle technology. Certain already existing vaccines, with modification, for example, acellular pertussis, have been adapted from use in infants for use in adolescents and adults. New fundamental knowledge on the intricacies of the innate immune system, in particular the role of Toll-like receptors, has revolutionized understanding of the relationship between the innate and adaptive immune systems, thereby providing a scientific underpinning to elevate adjuvant research from being largely empiric to becoming science based. This suggests that the next few years may see breakthroughs to enhance immune responses to poorly immunogenic vaccine antigens and to increase immunologic responses to vaccines in the very young and the elderly target groups that have, heretofore, been notoriously less immunologically responsive.

Technologies that allow high-throughput sequencing and bioinformatic analysis of genome sequence data have advanced at a frenzied pace. Many pathogens of interest for vaccine development have had their genomes sequenced, thereby allowing searches to be undertaken to identify antigens as potential targets to serve as vaccine candidates. The fourth edition very much highlights these technologies. This edition also continues the book's tradition of providing extensive descriptions of various live bacterial and viral vector vaccine strategies and technologies.

The entry of the Bill and Melinda Gates Foundation into the arena of vaccine development and implementation was recorded in the previous edition. In the ensuing years, the Foundation has greatly expanded the scope and breadth of its activities and has become a major supporter of research and development for HIV, malaria, and tuberculosis vaccines, as well as the primary funding source for an array of other vaccine development efforts for neglected diseases, including cholera, Shigella and enterotoxigenic Escherichia coli diarrheal pathogens, dengue, and Japanese encephalitis B virus, group A meningococcus, measles among infants too young to receive the currently licensed vaccine and hookworms.

The fourth edition provides an updated report on the extraordinary impact of the Global Alliance for Vaccines and Immunization (now called the GAVI Alliance) and its financial instrument, the Vaccine Fund. GAVI has become an established fact on the ground in developing countries and represents one of the most significant initiatives in vaccine public health since the establishment of the Expanded Program on Immunization in the 1970s. The GAVI Alliance partners, including the World Health Organization (WHO), UNICEF, the World Bank, the Bill and Melinda Gates Foundation, vaccine industry in both industrialized and developing countries, and others, are committed to increasing immunization coverage among infants in developing countries by strengthening the infrastructure of immunization services, introducing new vaccines (e.g., Haemophilus influenzae type b conjugate) into developing country programs and fostering the accelerated development and introduction of vaccines that can diminish young child mortality (multivalent pneumococcal conjugate and rotavirus vaccines). The fourth edition also updates both the impressive progress and the frustrating setbacks of the global Polio Eradication Initiative in recent years.

At the time of publication of the fourth edition, the supply of safe and effective vaccines was undergoing a fundamental change that reflected the dichotomy in the array of vaccines routinely administered to infants in the developing world versus infants and toddlers in the industrialized countries. Major vaccine producers in the developing world, most of which have evolved from government-supported facilities to become private profit-making entities, have successfully assumed the responsibility of providing most of the routine vaccines needed for infants in developing countries. These include major producers in India, China, Indonesia, and Brazil. That trend has continued and has reached the point where several of the more sophisticated vaccine manufacturers in developing countries have embarked on impressive research and development programs to construct, prepare pilot lot formulations, undertake large-scale manufacture process development, perform clinical trials, and submit to licensure by regulatory agencies several new vaccines targeted for use in developing countries. The fourth edition will relate several examples of such projects, including a monovalent meningococcal A conjugate and a method for delivering small particle–aerosolized attenuated measles vaccine.

The increasing role of manufacturers in the developing world in supplying vaccines for populations in those countries has resulted in the need to strengthen national regulatory agencies in those countries where vaccines are manufactured. Accordingly, a chapter has been added to the fourth edition to relate WHO's efforts to strengthen national regulatory agencies. In addition, the excellent chapter on the FDA as an example of the roles and responsibilities of a regulatory agency in handling biologics has been expanded.

The issue of ‘‘vaccine safety'' represents another area of striking dichotomy between vaccines used in the industrialized countries versus the developing world. In industrialized countries, where infectious diseases such as measles, poliomyelitis, and pertussis are rare, consequent to decades of immunization coverage, some segments of the population are becoming more focused on rare real or perceived adverse events related to vaccines rather than being concerned about the disease the vaccine aims to prevent. The trend is to expect ever higher levels of safety in relation to the use of vaccines. In contrast, in developing countries where measles and pertussis remain killers and polio stills paralyzes some unvaccinated individuals in certain countries, the emphasis is on protection against these diseases. As more countries transition to become industrialized, views about vaccine safety will undoubtedly change. These issues are becoming more relevant as it is increasingly recognized that the world is a ‘‘global village'' where modern travel allows pathogens that are still prevalent in developing countries but rare in industrialized countries to reappear with a vengeance in the latter if immunization coverage falls too low. Several chapters in the fourth edition acknowledge the notion that disease control is a shared global responsibility.

The previous edition had multiple chapters describing progress on therapeutic vaccines against chronic immunopathological diseases such as rheumatoid arthritis, multiple sclerosis and type 1 diabetes mellitus and of vaccinotherapy for cancer. In the ensuing years, these efforts have yielded many disappointments along with a few breakthroughs; so there is now considerable scientific retrenchment. The fourth edition of NGV addresses these changes with two scholarly, unbiased overview chapters that review, respectively, the immunotherapy of chronic diseases and cancer vaccinotherapy and relate progress in these areas. The fourth edition ratains several chapters that relate progress on the development of vaccines against certain other chronic progressive pathologies such as Alzheimer's disease.

The last edition also described preclinical studies with candidate antiaddiction vaccines. The fourth edition relates the progress as these vaccines have progressed to clinical trials with encouraging results and also addresses ethical issues that have arisen over the use of such vaccines.

One of the most significant changes in vaccine development since the last edition is in the area of vaccines against the highest threat bioterror agents and some emerging infectious disease agents, including human pandemic influenza. Notable investments in vaccine development have been made by the U.S. government to support the development of new vaccines against anthrax, smallpox, tularemia, an array of hemorrhagic fever viruses, and other emerging viruses (e.g., Ebola, Hendra, West Nile, SARS) and plague, as well as against other pathogens of potential bioterror concern (e.g., Shigella dysenteriae 1 and other Shigella). Accompanying these specific vaccine development efforts has been the corollary development of improved methods of immunizing populations en masse, in particular without the use of needles and syringes. The fourth edition has made a concerted effort to cover these exciting developments by including multiple chapters devoted to marking their progress.

Even with 89 chapters, it is impossible to include in a single text of research vaccinology updates on vaccines against every disease target and all new technologies. Thus, as with previous editions, there are some areas and topics where progress has been made that we have been unable to include. The editors have tried to minimize these voids. The editors would like to thank the many contributors who have provided outstanding chapters for the fourth edition. The editors extend their special thanks to family members, friends, and colleagues whose support and patience sustained our efforts to complete this edition during the many evening and weekend hours required to plan and edit this edition. The book could not have been completed without the competent assistance and diligence of Mrs Dottie Small and the ever available support, advice, and counsel of Ms Sandra Beberman and Aimee Laussen of Informa Healthcare.