USA ES IC V R E S N A M U H & D H H E T P L A A R E T H M F F E N O T Accelerated Development of Vaccines Preface In 1982, the National Institute of Allergy and Infectious Dis­ Along with these technological advances, there has been a eases (NIAID) established the Program for the Accelerated heightened awareness of the importance of vaccines for global Development of Vaccines. For 20 years, this program has helped health and security. Acquired immunodeficiency syndrome stimulate the energy, intellect, and ability of scientists in micro­ (AIDS), malaria, and tuberculosis have demonstrated to the biology, immunology, and infectious diseases. Vaccine research world the importance of public health in economic development. has certainly benefited. The status report reflecting this Most recently, the threat of bioterrorism has reminded many progress in vaccine research has come to be known as the Jor­ Americans of the value of vaccines as public health tools. dan Report in recognition of Dr. William Jordan, past director of NIAID’s Division of Microbiology and Infectious Diseases Articles by outside experts in this edition highlight many of the (DMID) and the program’s earliest advocate. scientific advances, challenges, and issues of vaccine research during these two decades. As we look to the decade ahead, the This anniversary edition of the Jordan Report summarizes 20 payoffs from basic research will continue to invigorate vaccine years of achievements in vaccine research driven by the explo­ development, but economic, risk communication, and safety sive technological advances in genomics, immunology, and challenges are likely to influence the licensing of new vaccines. molecular biology. Increased knowledge of the immune system The “easy” vaccines have been developed; many challenges lay has helped to define the mechanisms needed for successful ahead for new and improved vaccines. The emergent tools and immunization. Genomic tools are helping researchers identify enhanced interest, commitment, and resources that have been and fine-tune the targets most appropriate for use in developing developed in the preceding decades will be required to meet candidate vaccines. The payoffs from genomics are just begin­ these challenges. ning. Using tuberculosis as an example, in just 6 years research­ ers have sequenced the genome, have identified new targets for Carole Heilman, Ph.D. vaccine development, are working to analyze the function of Director more than 400 proteins, and are poised to conduct clinical evalu­ Division of Microbiology and Infectious Diseases ations of the first new candidate vaccines in 80 years. This year National Institute of Allergy and Infectious Diseases the Anopheles gambiae and Plasmodium falciparum genomes National Institutes of Health have been sequenced and, together with the human genome data, will allow researchers for the first time to listen in on immu­ nologic conversations of vector, pathogen, and host. The Jordan Report Acknowledgements This report was prepared under the supervision of the Division EXPERT ARTICLE CONTRIBUTING of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious Diseases (NIAID), National AUTHORS Institutes of Health (NIH). Dr. Carl R. Alving Dr. Maurice R. Hilleman Dr. Carole Heilman Dr. Pamela McInnes Ms. Sarah Landry Director Deputy Director Editor Dr. Norman W. Baylor Dr. William Jordan In addition to those who wrote special articles, sincere thanks Dr. Ann Bostrom Dr. Margaret A. Liu and appreciation are expressed to the staff of DMID for updat­ ing the scientific sections and the material presented in Appen­ Dr. Brenda Candries Dr. Loris D. McVittie dix C; to Ms. Alice Knoben, U.S. Food and Drug Administration, for reviewing and updating the material presented in Appendix Dr. Susan S. Ellenberg Dr. Julie Milstien D; to the staff of the Division of Acquired Immunodeficiency Syndrome for assembling the information in Appendices E and Dr. Geoffrey Evans Dr. Derek O’Hagan F; and to Dr. William Jordan for his continued enthusiasm for this important document. Dr. Anthony S. Fauci Dr. Stanley A. Plotkin A special thanks to Steve O’Krepky, Becky Lau, Louise Mr. Gregory K. Folkers Dr. Jeffrey B. Ulmer Dickerson, Judy Reemes, Bruce Dennis, Ann Hennigan, and Judy Zukoski at Analytical Sciences, Inc., for their help in de­ Dr. Mary A. Foulkes Dr. Frederick R. Vogel signing, compiling, and editing the report. Images, unless otherwise noted, were provided by the Centers for Disease Control and Prevention (CDC) image database. The Jordan Report Table of Contents EXPERT ARTICLES Candidiasis ........................................................ 101 Coccidioidomycosis .......................................... 102 History and Commentary ............................................ 1 Cryptococcosis ................................................. 103 The Ten Most Important Discoveries in Vaccinology Histoplasmosis .................................................. 104 During the Last Two Decades ............................... 18 Paracoccidioidomycosis .................................... 105 Pythiosis ............................................................ 106 Vaccines and the Vaccine Enterprise: Historic and Contemporary View of a Scientific Initiative Herpesvirus Infections ............................................. 107 of Complex Dimensions ....................................... 23 Overview .......................................................... 108 Cytomegalovirus ................................................ 111 Vaccine Technologies ................................................ 31 Varicella-Zoster Virus ........................................ 115 Progress in Immunologic Adjuvant Development: Epstein-Barr Virus ............................................. 117 1982-2002 ........................................................... 38 Jordan Perspective: Varicella Vaccine ................. 119 Changes in the Regulations for Vaccine Research and Human Immunodeficiency Virus (HIV) Disease ....... 120 Development ........................................................ 44 Overview .......................................................... 121 Recent Advances............................................... 121 Vaccine Efficacy and Safety Evaluation ...................... 50 Progression of Clinical HIV Research ................ 122 The Evolution of Vaccine Risk Communication in the Preclinical Developments ................................... 123 United States: 1982-2002 ..................................... 57 Challenges ......................................................... 124 Economics of Vaccine Development and Implementation: Conclusion ........................................................ 125 Changes Over the Past 20 Years ........................... 72 Parasitic and Tropical Infections .............................. 127 Vaccine Research and Development: The Key Roles of Overview .......................................................... 127 the National Institutes of Health and Other United Leprosy ............................................................ 128 States Government Agencies ................................. 80 Malaria ............................................................. 129 Schistosomiasis ................................................. 133 VACCINE UPDATES Other Parasitic Diseases ................................... .134 Respiratory Infections ............................................. 136 Enteric Infections ...................................................... 88 Overview .......................................................... 137 Overview ............................................................ 89 Bordetella Pertussis ......................................... 137 Cholera ............................................................... 89 Chlamydia Pneumoniae .................................. 140 Shiga Toxin-Producing E. Coli (STEC) Group AStreptococci........................................ 142 and Enteropathogenic E. Coli (EPEC) ............... 90 Group B Streptococci ....................................... 145 Enterotoxigenic E. Coli (ETEC) .......................... 90 Haemophilus Influenzae Type B ...................... 147 Helicobacter Pylori........................................... 91 Nontypeable Haemophilus Influenzae .............. 148 Polio ................................................................... 91 Influenza ............................................................ 150 Enteric Viruses .................................................... 94 Measles ............................................................ 152 Shigella ............................................................... 94 Mumps ............................................................. 154 Typhoid ............................................................... 95 Rubella .............................................................. 155 Campylobacter.................................................... 96 Meningococcal Disease ..................................... 156 Fungal Infections ....................................................... 97 Moraxella Catarrhalis ..................................... 158 Overview ............................................................ 98 Mycoplasma Pneumoniae................................ 159 Blastomycosis ................................................... 100 Parainfluenza Virus ............................................ 160 I Accelerated Development