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The Compelling Need for Game-Changing Influenza Vaccines

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THE COMPELLING NEED FOR GAME-CHANGING INFLUENZA VACCINES AN ANALYSIS OF THE INFLUENZA VACCINE ENTERPRISE AND RECOMMENDATIONS FOR THE FUTURE OCTOBER 2012 The Compelling Need for Game-Changing Influenza Vaccines An Analysis of the Influenza Vaccine Enterprise and Recommendations for the Future Michael T. Osterholm, PhD, MPH Nicholas S. Kelley, PhD Jill M. Manske, PhD, MPH Katie S. Ballering, PhD Tabitha R. Leighton, MPH Kristine A. Moore, MD, MPH The Center for Infectious Disease Research and Policy (CIDRAP), founded in 2001, is a global leader in addressing public health preparedness and emerging infectious disease response. Part of the Academic Health Center at the University of Minnesota, CIDRAP works to prevent illness and death from targeted infectious disease threats through research and the translation of scientific information into real-world, practical applications, policies, and solutions. For more information, visit: www.cidrap.umn.edu. This report was made possible in part by a grant from the Alfred P. Sloan Foundation. This report is available at: www.cidrap.umn.edu This report was produced and designed by Betsy Seeler Design. © 2012 Regents of the University of Minnesota. All rights reserved. Contents Preface...............................................................................................................................................................2 Executive Summary..........................................................................................................................................5 Chapter.1.. Understanding Influenza as a Vaccine-Preventable Disease.................................................10 Chapter.2... Currently Licensed Influenza Vaccines: Historical Perspective...............................................16 Chapter.3. Efficacy, Effectiveness, and Cost-Effectiveness of the Currently Licensed Influenza Vaccines.....................................................................................................................20 Chapter.4... How Safe Are Current Influenza Vaccines?.............................................................................35 Chapter.5... Public Acceptance of Influenza Vaccines.................................................................................40 Chapter.6... Seasonal and Pandemic Influenza Vaccine Availability .........................................................44 Chapter.7... Recommendations for Influenza Vaccine Use and Public Health Promotion .......................51 Chapter.8... Influenza Immunology: Infection, Current Vaccines, and New Developments....................65 Chapter.9... Potential Game-Changing Influenza Vaccines in the Research Pipeline: Framing the Discussion ............................................................................................................76 Chapter.10... Regulation of the Influenza Vaccine Enterprise.....................................................................84 Chapter.11.. Market Considerations, Challenges, and Barriers to Achieving Game-Changing Influenza Vaccines.....................................................................................................................92 Chapter.12... Public Health Policy Barriers to Achieving Game-Changing Influenza Vaccines ...............102 Chapter.13... Organization and Leadership Barriers to Achieving Novel-Antigen, Game-Changing Vaccines ......................................................................................................115 Chapter.14... Conclusions and Recommendations......................................................................................120 Appendix.A... List of Abbreviations..............................................................................................................124 Appendix.B....Reprint of Osterholm et al 2012 Lancet Infectious Diseases paper and Web appendix ...126 Preface ating back to Hippocrates, influenza has been many questions about the adequacy of our influenza and continues to be one of the “lion kings” of vaccine response. Dinfectious diseases. It occurs in two different patterns: (1) annual seasonal epidemics during winter In December 2009 the Alfred P. Sloan Foundation months in the temperate countries and year-round provided a grant to the Center for Infectious Disease in the tropics, and (2) global pandemics, which can Research and Policy (CIDRAP) at the University of occur during any season and last more than a year. An Minnesota to support the CIDRAP Comprehensive estimated 3,000 to 49,000 individuals in the United Influenza Vaccine Initiative (CCIVI). The primary States die every year from seasonal influenza. objectives of CCIVI were to provide a comprehensive review of all aspects of 2009-2010 pandemic Influenza pandemics occur when novel influenza A(H1N1)pdm09 influenza vaccine preparedness and viruses in animals undergo genetic changes that allow response based on the events of the pandemic vaccine the viruses to infect humans, who in turn transmit the effort and to review the scientific and programmatic new human-adapted virus to others. Four pandemics basis for the current seasonal influenza vaccine efforts. have occurred in the last 100 years: 1918, 1957, 1968, This review included all aspects of influenza vaccine and 2009. Influenza pandemics can vary in severity; research and development, financing, manufacturing, in 1918 an estimated 50 million to 100 million people efficacy, safety, regulatory issues, procurement, died worldwide. In the 1957 and 1968 pandemics, distribution, vaccine usage, public education, consumer an estimated 1.5 million and 750,000 people died, acceptance, and public policy. respectively. An official estimate of worldwide deaths from the 2009 pandemic is not expected until late 2012. And now, almost 3 years later, we share with you the completed CCIVI report; it represents one of the most Today more than 500 infectious diseases are known exhaustive reviews of any vaccine ever undertaken. When to occur in humans, yet in the United States, public we started, we had no idea where this initiative would health officials recommend routine childhood or adult take us. It was like peeling back the proverbial onion; vaccinations for only 17 of these diseases. And, for the more extensively we examined the “cradle to grave” only one of these diseases is there a recommendation aspects of our current seasonal and pandemic influenza for universal annual vaccination: namely, influenza. vaccines, the more questions—and lack of answers— In 2010 the Advisory Committee on Immunization we identified. In short, we found that current influenza Practices (ACIP) established the first national universal vaccine protection is substantially lower than for most seasonal influenza vaccination recommendation. routinely recommended vaccines and is suboptimal. It Annual vaccination is currently recommended with is clear, however, that during some influenza seasons trivalent inactivated influenza vaccine for all persons vaccination offers substantially more protection for most 6 months of age and older or with live-attenuated of the population than being unvaccinated. For this influenza vaccine for healthy nonpregnant persons reason, we believe current influenza vaccines will continue aged 2 to 49 years. Influenza vaccine availability also is to have a role in reducing influenza morbidity until more the cornerstone of influenza pandemic preparedness. effective interventions are available. But we can no longer accept the status quo regarding vaccine research and The Initiative development. In 2009, the world experienced its first influenza pandemic of the 21st century; it occurred 41 years This final CCIVI report includes 14 chapters and an after the previous one. Since the re-emergence of executive summary; it has 505 unique references. But H5N1 influenza in birds and humans in 2003 in to target the actions that we believe are necessary to Asia, the international public health community and move the international influenza vaccine enterprise influenza vaccine manufacturers have worked to toward critically needed novel-antigen, game-changing expand the global influenza vaccine manufacturing vaccines, we have identified just 10 key findings and capacity to respond to an emerging pandemic. six “high-level” recommendations. While our review However, early on in the 2009 pandemic there were and analysis effort was exhaustive, we have made every 2 effort to produce a report that allows the reader to The CCIVI Expert Advisory Group distinguish the forest from the trees! • Alfred Sommer, MD, MHS (Chair) Professor and Dean Emeritus, Johns Hopkins The Alfred P. Sloan Foundation generously provided Bloomberg School of Public Health unrestricted funding for the first year of the study • Ruth Berkelman, MD and allowed us to complete the final report when Director, Center for Public Health we finished our “onion peeling.” The remainder of Preparedness and Research, Emory University the support for this effort came from the general • Gail Cassell, PhD budget of CIDRAP and the ongoing efforts of a very Visiting Professor, Harvard Medical School dedicated CIDRAP team. We have no potential conflicts Ret. VP, Scientific Affairs and Distinguished of interest to report. In total, 13 CIDRAP staff and 2 Research Scholar, Eli Lilly and Company affiliated researchers provided thousands of hours of • Walt Dowdle, PhD painstaking “document detective work,” literature Consulting Director, the Task Force for Global review, and subject matter interviews. Health
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