H1N1 Swine Flu: The 2010 Perspective
Influenza viruses such as H1N1 continue to pose a major global public health problem, so understanding their pathogenicity and transmission is crucial. A symposium held on May 24, 2010, at the New York Academy of Sciences revisited the 2009 swine flu (H1N1) outbreak and examined strategies against future outbreaks. Invited speakers covered virulence, transmission, the New York City experience, vaccine development, and the public health implications of a worldwide pandemic. A roundtable discussion featuring all speakers then reflected on the successes and problems during the 2009 outbreak, debated whether this is now considered a rehearsal for more virulent outbreaks, and presented updated strategies to confront future pandemics.
In his examination of H1N1 virulence, Terrence Tumpey from the Centers for Disease Control and Prevention (CDC) discussed the use of a ferret model to investigate the pathogenesis and transmissibility of three 2009 H1N1 viruses compared with a seasonal H1N1 virus. Selected 2009 H1N1 isolates were assessed for their ability to cause disease, and were found to cause increased morbidity and exhibit less efficient respiratory droplet transmission in ferrets compared to the high-transmissible phenotype of a seasonal H1N1 virus. Anice Lowen of the Mt. Sinai School of Medicine reflected on transmission of the 2009 H1N1 pandemic influenza virus during the 2009 pandemic. Researchers studying the virus suggested that the 2009 pandemic strain spread with comparable or greater efficiency among humans than seasonal influenza viruses. It appeared that the unique constellation of gene segments comprising the 2009 H1N1 viral genome and/or adaptive changes that differentiate those gene segments from their swine precursors facilitated efficient human-to-human spread. Host and environmental factors also played a role in spread of the disease. The emergence of the swine-origin strain during the spring in the northern hemisphere was also important in shaping its epidemiology, as transmission continued throughout summer but peak influenza activity occurred later, during autumn and winter. Work in guinea pig models has found that aerosol transmission is dependent on humidity and temperature, suggesting that novel H1N1 epidemics will continue to adopt winter seasonality.
In a fascinating examination of pathology findings of all fatal 2009 influenza A/H1N1 viral infections seen in New York City, James Gill from the Office of Chief Medical Examiner summarized a review of all medical records, autopsy reports, microbiologic studies, and microscopic slides of the 34 people who died between May 15 and July 9, 2009. The majority of the 34 decedents (62%) were between 25 and 49 years of age, and most cases showed tracheitis, bronchiolitis, and diffuse alveolar damage. Bacterial pneumonia was detected in 55% of decedents, and underlying medical conditions (including cardiorespiratory diseases, immunosuppression, and obesity, as defined by a BMI >30) were associated with most deaths.
To address the role and response of the CDC, as the U.S. government primary front-line responder to all infectious disease outbreaks, Michael Shaw discussed their various pandemic response exercises, conducted in preparation for the appearance of new influenza pandemic strains. These preparedness assumptions were tested during the 2009 outbreak and required real-time reassessment and modification of response strategies. On reflection, systems put in place prior to the pandemic proved to be invaluable. Data and viruses were shared rapidly and openly, new diagnostic assays were deployed in record time, and a new vaccine (which proved to be an excellent match) was developed, tested, and dispensed with the cooperation of numerous government and private agencies and institutes. Lessons learned included the need for further strengthening of global surveillance systems, including animals; the need for improved vaccine technology and delivery to provide vaccines faster and more efficiently (particularly those vaccines not requiring refrigeration, for use in developing countries); and the usefulness of new media (including Twitter, Facebook, and YouTube) for disseminating important and useful messages to the community.
James Matthews from Sanofi Pasteur then provided an industry perspective on H1N1 vaccine development and deployment. Based on an avian virus outbreak in 1997, combined intelligence from the World Health Organization (WHO), various governments, and industry predicted that 'the next pandemic' would evolve from an avian H5N1 virus with origins in Southeast Asia. It was anticipated that the pandemic vaccine would likely be adjuvanted and probably require the administration of two doses in order to provide full protection. Surprisingly, the novel H1N1 virus appeared in April 2009 in North America, after it was assumed that subsequent pandemics would be of Southeast Asian and avian origin.
Despite the relatively short time from the 2009 H1N1 virus first being identified as a pandemic threat (April 2009) to the development and distribution of an H1N1 vaccine (September 2009), there is a continuing need to develop our capacity to shorten the duration to the first availability of the vaccine. To discuss new technologies in vaccine development, Jose Galarza of Technovax, Inc. discussed their efforts to develop a new way to produce highly immunogenic non-infectious monovalent and polyvalent influenza virus-like particle (VLP) vaccines. Improved production techniques have brought about many-fold increases in safe vaccine production without the need for inactivation, introducing the potential for higher yields in a reduced timeframe and at lower cost. Philip Dormitzer from Novartis Vaccines and Diagnostics then convened a panel discussion with all speakers.
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Presentations available from:
Doris Bucher (New York Medical College)
Terrence Tumpey (CDC)
Anice Lowen (Mt. Sinai School of Medicine)
James Gill (New York Office of Chief Medical Examiner)
Michael W. Shaw (CDC)
James T. Matthews (Sanofi Pasteur)
Jose M. Galarza (Technovax, Inc.)
This event is part of the Dr. Paul Janssen Memorial Series at the New York Academy of Sciences.
This program is supported by an educational grant from Gilead Sciences, Inc.
Doris Bucher, PhD
Doris Bucher is an associate professor in the Department of Microbiology and Immunology at New York Medical College. Bucher has dedicated most of her research career to work on influenza viruses and influenza vaccine development. Her laboratory at New York Medical College (NYMC) is one of only three laboratories worldwide which produce high growth reassortant 'seed' viruses for the influenza vaccine. For the past seven years (including 2010–2011), the NYMC H3N2 reassortants have been used either exclusively or for the bulk of world production of 400–450 million doses of influenza vaccine (inactivated). Shortly after identification of 2009 H1N1 (swine influenza) April, 21, 2009, by the CDC her laboratory was provided with the 2009 H1N1 isolate. Her laboratory group developed a reassortant virus 'seed' virus for the vaccine in about three weeks. This reassortant, NYMC X-179A, was used worldwide by manufacturers to produce most of the 2009 H1N1 vaccine (inactivated, egg based). Several weeks later her laboratory produced a second generation reassortant, NYMC X-181, with even better growth properties and many flu manufacturers continued production of swine flu vaccine with this reassortant. Flu vaccine manufacturers are now in full production for the 2010–2011 flu season. The vaccine formulation will include the 2009 H1N1 (NYMC X-179A or NYMC X-181), an H3N2 ('Perth-like' reassortant, NYMC X-187) and type B (B/Brisbane/60/2008 or the 'Brisbane-like' NYMC BX-35).
The Bucher lab is supported by a consortium of the major (and several minor) influenza vaccine manufacturers through their organization, IFPMA (International Federation of Pharmaceutical Manufacturers and Associations), Influenza Vaccine Supply International Task Force, based in Geneva.
Jennifer Henry, PhD
The New York Academy of Sciences
Jennifer Henry received her PhD in plant molecular biology from the University of Melbourne, Australia, with Paul Taylor at the University of Melbourne and Phil Larkin at CSIRO Plant Industry in Canberra, specializing in the genetic engineering of transgenic crops. She was then appointed as Associate Editor, then Editor, of Functional Plant Biology at CSIRO Publishing. She moved to New York for her appointment as a Publishing Manager in the Academic Journals division at Nature Publishing Group, where she was responsible for the publication of biomedical journals in nephrology, clinical pharmacology, hypertension, dermatology, and oncology.
Jennifer joined the Academy in 2009 as Director of Life Sciences and organizes 35–40 seminars each year. She is responsible for developing scientific content in coordination with the various life sciences Discussion Group steering committees, under the auspices of the Academy's Frontiers of Science program. She also generates alliances with outside organizations interested in the programmatic content.
Jose M. Galarza, DVM, PhD
Jose Galarza is CEO and founder of TechnoVax, Inc. a biotechnology company focusing on vaccine research and development. He has more than 28 years of scientific experience in the field of virology, molecular biology and vaccine development and is currently an adjunct associate professor of microbiology and immunology at the New York Medical College. Before founding TechnoVax, he was principal scientist and leader of the influenza subunit vaccine development program in the Vaccine Division of Wyeth, in Pearl River, New York. Galarza is the inventor of the influenza virus-like particle (VLP) vaccine technology, a platform with great potential for the creation and development of vaccines for a variety of targets. Prior to joining Wyeth, Galarza held research positions in the Department of Microbiology and Molecular Genetics, University of California at Irvine, Irvine, CA and in the Department of Cellular, Viral and Molecular Biology, at the University of Utah Medical Center in Salt Lake City, Utah. He is a member of numerous professional associations and serves as scientific reviewer, emphasis vaccines, for the Center of Scientific Review, National Institutes of Health (NIH). He holds a DVM and a doctorate in microbiology from the University of La Plata, La Plata, Argentina.
James Gill, MD
James Gill is a forensic pathologist and the deputy chief medical examiner of the Bronx Office of Chief Medical Examiner of the City of New York. His office investigates approximately 1,800 deaths per year and performs 1,100 autopsies. After receiving his bachelor's degree in Biology from MIT, he earned his medical degree from the University of Connecticut. He did his pathology training at Yale and Memorial Sloan-Kettering Cancer Center and is board certified in anatomic and forensic pathology. He is a clinical associate professor in the Department of Forensic Medicine at the New York University School of Medicine and has faculty appointments in the Departments of Pathology at the Yale School of Medicine and Albert Einstein School of Medicine.
Anice Lowen, PhD
Anice Lowen began her university studies at the University of Alberta (Edmonton, Canada), where she obtained her Bachelor of Science degree in the field of biochemistry. She then moved to the Institute of Virology in Glasgow, Scotland to join the laboratory of Richard Elliott. Lowen's work as a PhD student in the Elliott lab centered on reverse genetics of the tri-segmented, negative strand RNA virus, Bunyamwera virus. For her post-doctoral studies, Lowen moved to Mount Sinai School of Medicine (New York City) to work on influenza virus in the group of Peter Palese. During her post-doctoral studies, she developed the guinea pig as a model host for influenza virus transmission and then applied this system to identify viral, host, and environmental factors which impact viral spread. One important finding that stemmed from this work was the observation that aerosol transmission of influenza viruses is dependent on temperature and humidity, suggesting that these climatic factors could contribute to the seasonal epidemiology of influenza. Since July 2009, Lowen has continued her research on influenza virus transmission as an assistant professor in the Department of Microbiology at Mount Sinai School of Medicine.
James Matthews, PhD
James Matthews is vice president for health and science policy at Sanofi Pasteur. Matthews received his PhD from the University of Pennsylvania. After completing his fellowship at Harvard Medical School, Matthews was a senior research investigator at Bristol-Myers Squibb where his research focused on the identification of inhibitors of herpes and influenza viruses. Since joining Sanofi Pasteur, Matthews has been the principal scientist for a number of influenza vaccine research and development projects and a director for external research. Currently based in Washington DC, Matthews is responsible for coordinating all aspects of U.S. Government Non-commercial Contracts.
Michael W. Shaw, PhD
Michael Shaw received his PhD in microbiology from the University of Alabama in Birmingham in 1980 before doing postdoctoral research in the Virology Laboratory at the Rockefeller University in New York City. He has received a faculty position in Virology at the Rockefeller University and later worked in the Department of Epidemiology in the School of Public Health at the University of Michigan in Ann Arbor before joining the Centers for Disease Control and Prevention in 1993. He has worked with influenza viruses for more than 30 years with primary interests in the genetics and evolution of human and animal influenza strains. He currently serves as the associate director for laboratory science in the Influenza Division of the National Center for Immunization and Respiratory Disease at CDC in Atlanta. Most recently he was in charge of the 2009 H1N1 Pandemic laboratory activities at CDC overseeing and coordinating domestic and international laboratory responses.
Terrence M. Tumpey, PhD
Terrence M. Tumpey earned his Bachelor of Arts degree in biology from the University of Minnesota, Duluth and his PhD in microbiology/immunology from the University Of South Alabama School Of Medicine in Mobile, Alabama. He was a recipient of the American Society for Microbiology (ASM) Postdoctoral Fellowship award and conducted his postdoctoral training at the Influenza Division, Centers for Disease Control and Prevention (CDC). He later served the U.S. Department of Agriculture (USDA) as a microbiologist at the Southeast Poultry Research Laboratory in Athens, Georgia. Since 2003, Tumpey has been with the CDC and is currently a microbiologist and team leader of pathogenesis, within the Immunology and Pathogenesis Branch. His research on pathogenesis and immunity during the last 21 years is documented in 105 total peer-reviewed publications and in 2006 he was honored with the Lancet Award for the top scientific paper of 2005 presented by Lancet. He also received the 2006 and 2008 Shepard Award from the CDC for Outstanding Research Paper. Tumpey was appointed to the editorial board of the Journal of Virology in 2006 and in 2007 was inducted into the University of Minnesota, Duluth Academy of Science and Engineering.
Panel Discussion Chair
Philip R. Dormitzer, MD, PhD
Philip R. Dormitzer is head of the Viral Advanced Programs Global Project Team and a senior project leader for Viral Vaccine Research at Novartis Vaccines and Diagnostics in Cambridge, Massachusetts. He is a practicing physician, who is board certified in Internal Medicine. After studying anthropology at Harvard College and carrying out a field study of the Efe Pygmies in the Ituri Forest of the present-day Democratic Republic of Congo, Dormitzer completed his MD and PhD at Stanford University. His graduate research in the laboratory of Harry Greenberg focused on rotavirus antigenic structure. Dormitzer completed house-staff training in Internal Medicine at Massachusetts General Hospital and a fellowship in the Harvard Combined Infectious Diseases Training Program. He conducted his fellowship research in the Laboratory of Molecular Medicine, led by Stephen Harrison.
As an assistant professor of pediatrics at Harvard Medical School, Dormitzer led a structural virology laboratory. The Dormitzer group and its collaborators determined the structures of the rotavirus neutralization antigens by NMR spectroscopy, X-ray crystallography, and near atomic resolution electron cryomicroscopy. Dormitzer is a member of the editorial board of the Journal of Virology and coauthor of numerous articles in such publications as Nature, Science, PNAS, the EMBO Journal, the Journal of Virology, and the American Journal of Physical Anthropology. His writing for medical texts includes the chapters on rotaviruses for Mandell's Principles and Practices of Infectious Diseases, 6th and 7th editions. Since joining NV&D in 2007, Dormitzer has lead research on virus-like-particle vaccines and vaccines against respiratory viruses, including influenza and respiratory syncytial virus. He led the research component of the response to the H1N1 swine-origin influenza pandemic at NV&D, which rapidly developed and distributed three licensed pandemic influenza vaccines, including a cell-culture based vaccine. He is now responsible for advancing new viral vaccine candidates from research through clinical development, industrialization, and licensure.