THE JORDAN REPORT ACCELERATED DEVELOPMENT OF VACCINES 2012 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Allergy and Infectious Diseases Images on cover, from the top: Courtesy of the US Centers for Disease Control and Prevention; istock.com; Courtesy of the National Library of Medicine; Courtesy of MedImmune THE JORDAN REPORT ACCELERATED DEVELOPMENT OF VACCINES 2012 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Allergy and Infectious Diseases NIH Publication No. 11-7778 January 2012 www.niaid.nih.gov ADDITIONAL RESOURCES National Institute of Allergy and Infectious Diseases, www.niaid.nih.gov Vaccines.gov: your best shot at good health, www.vaccines.gov Centers for Disease Control and Prevention: Immunization Schedules, www.cdc.gov/vaccines/recs/schedules/ Table of Contents INTRODUCTION VACCINE UPDATES Foreword by Anthony S. Fauci, M.D. ......................................... 3 Dengue M. Cristina Cassetti, Ph.D. .......................................................... 95 Tribute by Carole A. Heilman, Ph.D. ......................................... 5 HIGHLIGHT BOX Vaccine Against Chikungunya Virus in Development EXPERT ARTICLES Gary J. Nabel, M.D., Ph.D. and Ken Pekoc ......................... 97 Vaccinomics and Personalized Vaccinology Severe Acute Respiratory Syndrome Gregory A. Poland, M.D., Inna G. Ovsyannikova, Ph.D. and Frederick J. Cassels, Ph.D. ............................................................ 98 Robert M. Jacobson, M.D. .............................................................11 HIGHLIGHT BOX Sex Differences in Immune Responses to Vaccines Vaccine Delivery Technologies Col. Renata J. M. Engler, M.D. and Mary M. Klote, M.D. ....... 19 Martin H. Crumrine, Ph.D. ................................................. 105 Immunization and Pregnancy West Nile Virus Flor M. Munoz, M.D. .................................................................. 27 Patricia M. Repik, Ph.D. ............................................................. 106 HIGHLIGHT BOX Second-Generation Malaria Vaccines: A Definitive End to Malaria-Related Deaths? Henipaviruses (Nipah Virus and Hendra Virus) Vasee S. Moorthy, MRCP, Ph.D. .................................................. 34 M. Cristina Cassetti, Ph.D. .................................................. 109 Structural Biology and Other Resolution-Enhancing Group B Streptococcus Technologies in the Design of an Effective HIV–1 Vaccine Xin-Xing Gu, M.D., Linda C. Lambert, Ph.D. and Peter D. Kwong, Ph.D., John R. Mascola, M.D. and Carol Baker, M.D. .........................................................................110 Gary J. Nabel, M.D., Ph.D. ........................................................... 40 HIGHLIGHT BOX CMV Vaccine Shows Promise New Methods for Analyzing Vaccine Responses Walla Dempsey, Ph.D., M. Cristina Cassetti, Ph.D. Mark M. Davis, Ph.D. and John D. Altman, Ph.D. ................... 46 and Mason Booth ...................................................................114 Developing Vaccines for the Neglected Tropical Diseases HIV/AIDS David J. Diemert, M.D., FRCP(C) and Rona L. Siskind, M.H.S. ...............................................................115 Saman Moazami, B.A. .................................................................. 53 HIGHLIGHT BOXES The Public Health Need for a Staphylococcus aureus Vaccine Herpevac Trial for Women Concludes Scott K. Fridkin, M.D. and John A. Jernigan, M.D., M.S. ........ 66 Amanda Schleif, M.P.H. ....................................................... 120 Adjuvants—Past, Present, and Future Chlamydia Vaccine Being Tested in Nicholas I. Obiri, Ph.D. and Nonhuman Primates Nathalie Garçon, Pharm.D., Ph.D. ..............................................74 Harlan D. Caldwell, Ph.D. and Ken Pekoc ........................ 122 Progress, Promises, and Perceptions: The National Vaccine Promising HIV Vaccine Trial Results: RV144, Plan—A Path Forward for the Coming Decade the Thai HIV Vaccine Trial Bruce G. Gellin, M.D., M.P.H. and Sarah R. Landry, M.A. ..... 85 Rona L. Siskind, M.H.S. ....................................................... 126 1 Influenza Linda C. Lambert, Ph.D. and Frederick J. Cassels, Ph.D. ...... 127 HIGHLIGHT BOX NIAID Centers of Excellence for Influenza Research and Surveillance Sarah E. Miers, J.D. ............................................................... 132 Malaria Peter D. Crompton, M.D., M.P.H. and Steven R. Rosenthal, M.D., M.P.H. ................................................................................ 133 HIGHLIGHT BOX The International Centers of Excellence for Malaria Research Malla R. Rao, Dr.P.H., M.Eng. ............................................ 134 Respiratory Syncytial Virus Sonnie Kim, M.S. ......................................................................... 139 HIGHLIGHT BOX Impact of Regulatory Science on Influenza Vaccine Development David S. Cho, Ph.D., M.P.H. ................................................ 139 Tuberculosis Christine F. Sizemore, Ph.D. ...................................................... 144 HIGHLIGHT BOX Hepatitis C Virus: Prospects for Vaccine Development Sarah E. Miers, J.D. and Rajen Koshy, Ph.D. .................... 147 Rotavirus Diana S. Berard ........................................................................... 149 APPENDIXES Appendix A: Status of Vaccine Research and Development, 2012...................................................................... 153 Appendix B: NIAID-Supported HIV Vaccine Candidates in Preclinical Development ............................................................ 179 Appendix C: Ongoing Clinical Trials of HIV Vaccine Candidates in HIV-Uninfected Adults .................................... 180 2 THE JORDAN REPORT 2012 Foreword to 2012 Jordan Report Anthony S. Fauci, M.D., National Institute of Allergy and Infectious Diseases, National Institutes of Health n 1981 the National Institute of Allergy and Infectious Diseases (NIAID) recognized the critical role vaccines Ihave played in preserving human life and human health by initiating the Program for the Accelerated Development of Vaccines. The goal of this program was to build on 20th century vaccine triumphs against such important infectious diseases as diphtheria, measles, pertussis, poliomyelitis, tetanus, yellow fever, and others. Conceived of by NIAID scientist John R. Seal (1912–1984), the new program was ably directed for 6 critical early years by William S. (Bill) Jordan (1917–2008). After retirement in 1987, Dr. Jordan stayed involved with NIAID, and particularly in vaccine research, for another 20 years, time enough to teach and influence a new generation of NIAID scientists who today continue the tradi- tion in support of the vaccine goals first articulated in 1981. Progress in vaccine development is periodically reviewed and published by NIAID scientists in what has come to be called, with the affection and admiration of his colleagues, The Jordan Report. Drs. Seal and Jordan are sadly no longer with us, but after an eventful 30 years the initiative they started remains healthy and vigorous. As discussed in greater depth in this report, progress in vaccine development has moved continuously forward, sometimes leaping ahead while at other times seeming to crawl. Looking back at the challenges of 30 years ago, however, it is undeniable that there have been remarkable achievements. We now have licensed vaccines against Haemophilus influenzae type B and pneumococcal types that cause high childhood morbidity and mortality, against hepatitis A and B, against rotaviruses, and against varicella. We also have improved vaccines against such diseases as influenza and pertussis, and passive immunotherapy against respiratory syncytial virus (RSV) in newborns. In addition to technological advances in making vaccines, including protein conjugation of bacterial polysaccharides, Top: A grade school boy, held by a young woman wearing a safety patrol belt, DNA vaccines, viral chimeras, viral vectors, and other novel is about to receive an immunization from a nurse (circa 1940). Courtesy of the platforms, the last 30 years also have been characterized by National Library of Medicine noteworthy advances in delivering vaccines to the developing Bottom: Aerial view of a crowd awaiting polio immunization at a city auditorium in San Antonio, TX (1962). Courtesy of CDC/Mr. Stafford Smith world. Public health programs, supported by governments and energetic philanthropic foundations, have had extraordinary FOREWORD 3 success in reducing childhood mortality. Poliomyelitis is now delivery of lifesaving vaccines to the world’s poorest nations. on the brink of elimination, and global measles mortality has NIAID and other global health leaders have joined this initia- been markedly reduced in recent years, with eradication a tive, which seeks to dramatically reduce child mortality and possibility. New vaccines against rotaviruses, which kill half save millions of lives by 2020. a million children annually, are already having an important Some of the successes we have enjoyed and the challenges beneficial effect in the developing world and promise an enor- we now face are highlighted in this report. After 30 years, it mous impact in reducing mortality in coming years. Vaccines has become clear that vaccines will remain critical to human against pneumococci and Haemophilus influenzae type B health for the foreseeable future and that development and already