Vaccine Research
and Development
to Advance Pandemic
and Seasonal
Influenza Preparedness
and Response
Lessons from COVID-19
Enriqueta Bond, Kanta Subbarao, and Hoda Soltani, Editors
Committee on Vaccine Research and Development Recommendations
for Advancing Pandemic and Seasonal Influenza Preparedness
and Response
Board on Global Health
Health and Medicine Division
A Consensus Study Report of
and
NATIONAL ACADEMY OF MEDICINE
THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu
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This activity was supported by a contract between the National Academy of Sciences and the Office of Global Affairs with the U.S. Department of Health and Human Services. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.
International Standard Book Number-13: 978-0-309-08781-0
International Standard Book Number-10: 0-309-08781-3
Digital Object Identifier: https://doi.org/10.17226/26282
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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2022. Vaccine research and development to advance pandemic and seasonal influenza preparedness and response: Lessons from COVID-19. Washington, DC: The National Academies Press. https://doi.org/10.17226/26282.
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COMMITTEE ON VACCINE RESEARCH AND DEVELOPMENT RECOMMENDATIONS FOR ADVANCING PANDEMIC AND SEASONAL INFLUENZA PREPAREDNESS AND RESPONSE1
ENRIQUETA BOND (Co-Chair), Founding Partner, QE Philanthropic Advisors
KANTA SUBBARAO (Co-Chair), Director, Collaborating Centre for Reference and Research on Influenza, World Health Organization
MARIA ELENA BOTTAZZI, Associate Dean, National School of Tropical Medicine; Professor of Pediatrics and Co-Director, Texas Children’s Center for Vaccine Development, Baylor College of Medicine; Co-Chair, Vaccines and Therapeutics Taskforce, Lancet Commission on COVID-19
REBECCA J. COX, Professor of Medical Virology and Head of the Influenza Centre, University of Bergen and Haukeland University Hospital
ANNETTE FOX, Senior Research Scientist, Collaborating Centre for Reference and Research on Influenza, World Health Organization
FLORIAN KRAMMER, Professor of Microbiology, Department of Microbiology, Icahn School of Medicine at Mount Sinai
GRACE M. LEE, Professor of Pediatrics, Stanford University School of Medicine JOHN C. MARTIN (until March 30, 2021, deceased), former Chief Executive Officer and Executive Chairman, Gilead Sciences
JOSHUA M. SHARFSTEIN, Professor of the Practice in Health Policy and Management, Johns Hopkins Bloomberg School of Public Health
MILAGRITOS D. TAPIA, Professor, Pediatrics, University of Maryland School of Medicine
Study Staff
HODA SOLTANI, Study Director
EMILIE RYAN-CASTILLO, Senior Program Assistant
ELIZABETH ASHBY, Research Associate
HANNAH K. COLLINS, Research Associate
PATRICIA A. CUFF, Senior Program Officer
JULIE A. PAVLIN, Senior Director, Board on Global Health
Consultant
MAARTJE WOUTERS, Science Writer
___________________
1 See Appendix B, Disclosure of Unavoidable Conflict of Interest.
In Memoriam
John C. Martin, Ph.D., M.B.A.
1951–2021
Reviewers
This Consensus Study Report was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process.
We thank the following individuals for their review of this report:
Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations of this report nor did they see the final draft before its release. The review of this report was overseen by ANN M. ARVIN, Stanford University School of Medicine, and ALASTAIR J. WOOD, Vanderbilt University. They were responsible for making certain that an independent
examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.
National Academy of Medicine
Advancing Pandemic and Seasonal Influenza Vaccine Preparedness and Response Series
This study, Vaccine Research and Development to Advance Pandemic and Seasonal Influenza Preparedness and Response: Lessons from COVID-19, provides recommendations on how to leverage the knowledge gained from the COVID-19 pandemic to optimize research and development for future pandemic and seasonal influenza vaccines. It is one of four studies conducted under the Advancing Pandemic and Seasonal Influenza Vaccine Preparedness and Response Initiative, which explores how the scientific and technological breakthroughs throughout the COVID-19 pandemic could inform and advance future pandemic and seasonal influenza vaccine preparedness and response efforts.
The three companion studies to this study examine how the lessons learned from COVID-19 around vaccine distribution and supply chain contingencies, public health interventions and countermeasures, and global coordination, partnerships, and financing could be best utilized to improve the development and distribution of future pandemic and seasonal influenza vaccines. Together, the four studies present a path toward better preparedness in addressing pandemic and seasonal influenza.
Launched by the National Academy of Medicine with support from the Office of Global Affairs, U.S. Department of Health and Human Services, the Advancing Pandemic and Seasonal Influenza Vaccine Preparedness and Response Initiative acknowledges that influenza is here to stay. The unprecedented scope of this initiative allowed for international experts to look at this issue from multiple angles and provide recommendations that set out a pathway to more effective influenza vaccines worldwide. Driven by international cooperation, this independent initiative provides a platform to highlight why we need to act as a global community to better prepare for pandemic and seasonal influenza.
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Acknowledgments
The committee has been honored and privileged to be able to contribute to this important effort and wishes to acknowledge the valuable contributions and assistance of many individuals who shared their expertise. The Statement of Task was developed by an international committee of experts assembled by the National Academy of Medicine. Many thanks to many area experts who volunteered their time to present to the committee and provided invaluable insights to inform the recommendations in this report. In this vein, we extend our thanks to Ben Cowling (University of Hong Kong); Barney Graham (NIH); Rita Helfand (WHO); Robert Johnston (BARDA); David Kaslow (PATH); Jerome Kim (International Vaccine Institute); Nicole Lurie (CEPI); Peter Marks (FDA); Kathleen Neuzil (University of Maryland – Center for Vaccine Development); Julie Ostrowsky (CIDRAP); Rino Rappuoli (GlaxoSmithKlein); Nadine Rouphael (Emory Vaccine Center); and Melanie Saville (CEPI). Finally, we thank the outstanding support and work of the National Academies of Sciences, Engineering, and Medicine project staff for overseeing the assembly of our committee and the details of this report. We deeply appreciate the work of Hoda Soltani, Study Director; Emilie Ryan-Castillo, Senior Program Assistant; Elizabeth Ashby, Research Associate; Hannah Collins, Research Associate; Patricia Cuff, Senior Program Officer; and Julie Pavlin, Senior Director, Board on Global Health. This project would not be possible without the support of the Office of Global Affairs at the U.S. Department of Health and Human Services.
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Preface
The National Academy of Medicine (NAM) has established an international committee in coordination with the U.S. Department of Health and Human Services’ Office of Global Affairs (OGA) to inform and facilitate efforts to advance global influenza pandemic preparedness. This international committee will provide OGA with an iterative, interactive multidisciplinary process for assessing the global effect that capabilities, technologies, processes, and policies developed for COVID-19 pandemic could have on pandemic and seasonal influenza global preparedness and response, especially regarding vaccine development. As part of the NAM initiative, the National Academies of Sciences, Engineering, and Medicine are carrying out four concurrent consensus studies. As one of the four work streams of this effort, our committee examined the technological and scientific advances achieved during the global response to COVID-19 and other outbreaks to distill lessons learned for vaccine research, development, and manufacturing, including the use of platform technologies to recommend strategies to harness the science, technology, policy, and practice required to improve global influenza pandemic preparedness and response.
In the 1980s as the United States mounted a response to address the harsh realities of the HIV/AIDS pandemic, Nobel laureate Joshua Lederberg warned that the public and political leadership of the United States needed to seriously address emerging infectious diseases and their potential for devastating epidemics. In 1992 the Institute of Medicine (IOM) published the landmark report Emerging Infections: Microbial Threats to Health in the United States, which pointed to major challenges for the public health and medical care communities in detecting and managing infectious disease
outbreaks and monitoring the prevalence of endemic diseases. A decade later Microbial Threats to Health: Emergence, Detection, and Response, underscored the revolution in globalization of all spheres including political, economic, cultural, technological, and informational—a new global environment where infectious agents could migrate with the internationalization of goods and people.
The severe acute respiratory syndrome (SARS), the Middle East respiratory syndrome, and Ebola serve as classic examples for how diseases can emerge and reemerge with unexpected fluctuations in different parts of the world. Fortunately, each was controlled before it grew into a pandemic. Then SARS coronavirus 2 (SARS-CoV-2) emerged, causing the COVID-19 pandemic, with dramatic loss of human life and devastating social and economic disruption worldwide. In October 2020, Cutler and Summers estimated the costs of COVID-19 in the United States at $16 trillion. As of August 2021, the Johns Hopkins University map notes that globally there have been nearly 190 million cases, more than 4 million recorded deaths, though some estimate total deaths may be as high as 16 million, and nearly 3.6 billion courses of vaccine administered. While an unprecedented number of vaccines has been developed, much more needs to be done to reach the nearly 8 billion human beings on Earth. The pandemic continues as variants have emerged.
Most experts believe that an influenza pandemic is inevitable given (1) the circulation of different influenza A subtypes in animals, (2) current global circulation of two A subtypes in humans, and (3) the ability of the viruses to mutate and reassort. In the early 20 century, the Spanish influenza caused an estimated 50 million deaths worldwide. Additional influenza pandemics in 1957, 1968, and 2009 claimed lower numbers of lives but still had an enormous impact on global human health and the economy. For this reason, for several years, governments, philanthropy, and global organizations have focused much attention to influenza pandemic preparedness planning. These efforts certainly facilitated the scientific and public health response to COVID-19, but they fell short, as we have seen with the inequities and the inability to vaccinate all. In the process of responding to COVID-19, lessons learned can be deployed to help the world respond better to the next influenza pandemic.
The main lesson has been that, given the astonishing and devastating costs to human life and the global economy, many more resources need to be sustainably invested in continued research, platform development for new influenza vaccines, and the regional capacity to research, manufacture, and distribute vaccines. Unprecedented cooperation and coordination among the different academic, government, industry, philanthropic, and global organizations have facilitated COVID-19 vaccine development and provided models for the future, but more needs to be done to ensure that
low- and middle-income countries also benefit and that we do not lose momentum in preparing ourselves for a future influenza pandemic.
Enriqueta Bond, Co-Chair
Kanta Subbarao, Co-Chair
Committee on Vaccine Research and Development
Recommendations for Advancing Pandemic and Seasonal Influenza Preparedness and Response
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Boxes and Figures
BOXES
2-1 Basic and Translational Science: Lessons Learned from the COVID-19 Pandemic
3-1 Clinical Science: Lessons Learned from the COVID-19 Pandemic
4-1 Manufacturing Science: Lessons Learned from the COVID-19 Pandemic
4-3 Gaps and Challenges for the Use of mRNA-based Vaccines as a Tool for Influenza Preparedness
4-4 Essential Responsibilities and Functions of Manufacturers
4-5 Attributes of Effective Manufacturing Technology Transfer During Pandemics
5-1 Regulatory Science: Lessons Learned from the COVID-19 Pandemic
FIGURES
1-1 Mapping the major elements of the committee’s Statement of Task to the chapters of this report
1-2 A history of global pandemics
1-3 The COVID-19 vaccine development timeline
2-1 Coalition for Epidemic Preparedness Innovations–supported COVID-19 vaccines in development
4-1 Estimated potential annual pandemic production capacity over time (since 2006)
4-2 Countries reporting adult immunization programs by vaccine type and WHO region
4-3 Countries reporting adult immunization programs by vaccine type and income level
4-4 Countries with influenza vaccine production capacity in 2019
Acronyms and Abbreviations
| Ad26 | adenovirus serotype 26 |
| BARDA | Biomedical Advanced Research Development Authority |
| CDC | U.S. Centers for Disease Control and Prevention |
| CEPI | Coalition for Epidemic Preparedness Innovations |
| CIDRAP | Center for Infectious Disease Research and Policy |
| CMC | chemistry, manufacturing, and control |
| COBRA | computational optimized broadly reactive antigens |
| CONSISE | Consortium for the Standardization of Influenza Seroepidemiology |
| COVID-19 | coronavirus disease 2019 |
| CVD | Centre pour le Developpement des Vaccins |
| DNA | deoxyribonucleic acid |
| EMA | European Medicines Agency |
| EUA | Emergency Use Authorization |
| FDA | U.S. Food and Drug Administration |
| FLUCOP | Standardization and Development of Assays for Assessment of Influenza Vaccine Correlates of Protection |
| GAP | Global Action Plan |
| GISAID | Global Initiative on Sharing All Influenza Data |
| GISRS | Global Influenza Surveillance and Response System |
| HA | hemagglutinin |
| HHS | U.S. Department of Health and Human Services |
| HI | hemagglutinin inhibition |
| HIC | high-income country |
| ICMRA | International Coalition of Medicines Regulatory Authorities |
| IHR | International Health Regulations |
| IP | intellectual property |
| LMIC | low- and middle-income country |
| mAb | monoclonal antibody |
| MDCK | Madin-Darby canine kidney |
| MERS | Middle East respiratory syndrome |
| NA | neuraminidase |
| NAM | National Academy of Medicine |
| NIAID | National Institute of Allergy and Infectious Diseases |
| NIH | National Institutes of Health |
| NK | natural killer |
| OWS | Operation Warp Speed |
| PRR | pattern recognition receptor |
| QIV | quadrivalent inactivated vaccine |
| R&D | research and development |
| SARS | severe acute respiratory syndrome |
| SARS-CoV-2 | severe acute respiratory syndrome coronavirus 2 |
| SPEAC | Safety Platform for Emergency vACcines |
| TIV | trivalent inactivated vaccine |
| TTS | thrombosis with thrombocytopenia syndrome |
| UIV | universal influenza vaccine |
| VAERS | Vaccine Adverse Event Reporting System |
| VE | vaccine effectiveness |
| VSD | Vaccine Safety Data Link |
| WHO | World Health Organization |
| YODA | Yale Open Data Access |
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