THE JORDAN REPORT ACCELERATED DEVELOPMENT OF VACCINES 2007 U. S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Allergy and Infectious Diseases NIH Publication No. 06-6057 May 2007 www.niaid.nih.gov Images on cover, clockwise from top: © The World Bank; Courtesy of the National Library of Medicine; istock.com; Courtesy of the National Library of Medicine Table of Contents INTRODUCTION VACCINE UPDATES Introduction by Carole Heilman, Ph.D. .....................................3 Supporting the Nation’s Biodefense .........................................69 Animal Models for Emerging Infectious Diseases Tribute to Maurice R. Hilleman, Ph.D., and John R. La Montagne, Ph.D., by William S. Jordan, Jr., M.D. .....................5 Hepatitis C..................................................................................75 HIV/AIDS ...................................................................................77 EXPERT ARTICLES Dale and Betty Bumpers Vaccine Research Center The Immunology of Influenza Infection: Implications Human Papillomavirus (HPV) .................................................87 for Vaccine Development Cancer Vaccine Development at NCI Kanta Subbarao, M.D., M.P.H., Brian R. Murphy, M.D., Influenza .....................................................................................89 and Anthony S. Fauci, M.D........................................................11 Malaria ........................................................................................95 Vaccine Production and Supply: Vulnerabilities in the Present System Severe Acute Respiratory Syndrome (SARS)..........................103 Walter A. Orenstein, M.D., Alan R. Hinman, M.D., Streptococcus Pneumoniae......................................................109 M.P.H., Lance E. Rodewald, M.D. .............................................21 The Gambia Pneumococcal Vaccine Trial Project BioShield: A Tool for Developing, Using, and Tuberculosis..............................................................................113 Stockpiling Needed Public Health Emergency Medical Countermeasures Varicella-Zoster Virus...............................................................119 Noreen A Hynes, M.D., M.P.H. .................................................27 West Nile Virus.........................................................................123 Using Genomics to Identify Novel Vaccine Candidates Against Pathogens APPENDIXES Hervé Tettelin, Ph.D., Rino Rappuoli, Ph.D., and Claire M. Fraser-Liggett, Ph.D...................................................37 Appendix A: Status of Vaccine Research and Development .....................................................................127 Adolescent Immunizations: Will the Shots Hit Their Targets? Amy B. Middleman, M.D., M.P.H., M.S.Ed..............................43 Appendix B: Vaccines Licensed for Immunization and Distribution in the United States ............................................141 Phase IIB/Test of Concept Trials for HIV Vaccine Efficacy Evaluation Appendix C: HIV Vaccine Candidates in Preclinical Susan P. Buchbinder, M.D. ........................................................53 Development ............................................................................145 The Animal Rule from a Vaccine Development Perspective Appendix D: Clinical Trials of HIV Vaccine Candidates in Mark J. Abdy, D.V.M., Ph.D., Michael Merchlinsky, Ph.D., and HIV-Uninfected Adults............................................................147 Drusilla L. Burns, Ph.D. .............................................................61 Appendix E: Recommended U.S. Childhood Immunization Schedule...........................................................151 Appendix F: Recommended U.S. Adult Immunization Schedule ....................................................................................155 THE JORDAN REPORT 2007 1 2 THE JORDAN REPORT 2007 Introduction Carole Heilman, Ph.D. binant DNA. Scientists also continue to additional benefit of the vaccine may be improve existing vaccines and identify to decrease transmission of B. pertussis new vaccine candidates to prevent diseases to infants, who are particularly vulnerable Background for which no vaccines currently exist. By to severe illness from B. pertussis.The t has been almost 25 years since the increasing their understanding of the illness affects 50 million people world­ first vaccine research and development immune system and how it fights off wide each year. I“state of the science” report, otherwise harmful microbes, researchers have also known as The Jordan Report, was pub­ made exciting developments in vaccine Challenges and Opportunities lished by the National Institute of Allergy research methodology, which have Despite considerable progress in vaccinol­ and Infectious Diseases (NIAID), part of resulted in recent clinical trials to evaluate ogy, the emergence of new infectious the National Institutes of Health. Since candidate vaccines against malaria, diseases, the re-emergence of old diseases, that time, significant scientific progress tuberculosis and West Nile virus. and the persistence of intractable diseases has been made in developing new and An exciting scientific milestone (sometimes due to drug resistance), better vaccines against a wide array of occurred in January 2004, when a new make infectious diseases some of the infectious diseases, including those that tuberculosis vaccine entered Phase I most complex and difficult challenges are emerging or re-emerging. clinical trials. NIAID has supported facing the public health community today. Historically, vaccines have led to some research on this candidate vaccine since HIV/AIDS, malaria, and tuberculosis of the greatest public health triumphs ever, its earliest stages. The vaccine was the are still among the leading killers world­ including the eradication of naturally- first to reach human trials in the United wide and no licensed vaccines against occurring smallpox from the globe more States and, in fact, the first new tubercu­ them currently exist. In addition, new than 50 years ago, and the near-eradication losis vaccine to be tested in more than infectious diseases continue to emerge. of polio. In addition, there has been a 60 years. Since the last edition of The Jordan significant reduction in the disease burden Childhood and adolescent vaccines Report, the world has seen an outbreak imposed by measles, mumps, hepatitis, are another area in which significant of a novel coronavirus termed “severe influenza, diphtheria, and many other advances have been made. In March acute respiratory syndrome” (SARS), infections. 2005, global health leaders presented new yearly West Nile virus outbreaks, and This edition of the Jordan Report research findings showing that vaccinating most recently, the continuing threat of a outlines a number of significant advances infants against Streptococcus pneumoniae— potential avian influenza pandemic. made in infectious disease vaccine a bacterium that causes deadly pneumonia, Even as infectious diseases emerge research and development since the last meningitis, and sepsis—could substan­ and re-emerge, however, scientists con­ document was published in 2002. In tially reduce death and serious illness tinue to rapidly develop and design addition, it offers a variety of perspectives among children in the developing world. novel vaccine approaches. These include from experts in the field on timely This study, The Gambia Pneumococcal developing new adjuvants and novel immunization topics, including adolescent Vaccine Trial, was supported in part by delivery systems such as oral, nasal, vaccine platforms and vaccine supply. the NIAID. transcutaneous vaccinations, and com­ In October 2005, study results were bination vaccine strategies. In addition, Advances in Vaccine Research released for the NIAID-supported acellular the application of genomic and post- and Development pertussis trial, which showed that the genomic technologies in the development One factor contributing to the rapid candidate vaccine was more than 90 of a new generation of tailor-made expansion of the current vaccine arsenal percent effective in preventing the trans­ vaccines has the potential to provide a is the acceleration of technological mission of B. pertussis in people between stunning opportunity to “customize” advances, including those using recom­ the ages of 15 and 65. An important vaccines against novel microbes. INTRODUCTION 3 There is also great enthusiasm and renewed effort for exploring opportunities for vaccine development in less traditional areas. These areas include therapeutic vaccines for managing chronic diseases, vaccines for controlling autoimmune dis­ eases, and vaccines against diseases of particular public health concern that have implications for global health. Positive Spin-offs of Basic Research NIAID’s investment in research on biode­ fense pathogens will have many positive implications for global public health. Studies of microbial biology and the pathogenesis of organisms with bioterror potential will lead to a better under­ standing of other, more common and naturally occurring infectious diseases and advance future vaccine development pathways and strategies. Furthermore, this research promises to enhance the understanding of molecular and cellular mechanisms (including regulation) of the immune system, which may help in the search for new ways to treat and prevent a variety of immune-mediated diseases