H1N1 Swine Flu: the 2010 Perspective

Agenda

Abstracts

Transmission and Pathogenesis of H1N1 Influenza Viruses in Ferrets

Terrence M. Tumpey, Centers for Disease Control and Prevention

In March 2009 an influenza A H1N1 virus variant was introduced into the human population and continues to cause illness in regions of the world. We have developed a comparative ferret model that parallels the efficient transmission of seasonal influenza viruses and the poor transmission of avian H1N1 influenza viruses in humans. The ferret model provides both contact and respiratory droplet transmission evaluation of influenza viruses. Selected 2009 H1N1 isolates were assessed for their ability to cause disease in ferrets, and compared with a contemporary seasonal H1N1 virus for their ability to transmit by respiratory droplets to naïve ferrets. In contrast to seasonal influenza H1N1 virus, 2009 H1N1 viruses caused increased morbidity, replicated to higher titers in lung tissue and were recovered from the intestinal tract of intranasally inoculated ferrets. The 2009 H1N1 viruses exhibited less efficient respiratory droplet transmission in ferrets in comparison to the high-transmissible phenotype of a seasonal H1N1 virus. These results along with pathogenesis and transmission data from other H1N1 viruses will be presented and may provide further insight into the current H1N1 pandemic virus.

Transmission of the 2009 H1N1 Pandemic Influenza Virus

Anice Lowen, Mount Sinai School of Medicine

Novel, swine origin influenza viruses of the H1N1 subtype were first detected in humans in April 2009; by the 11th of June, human-to-human transmission had become so widespread that the WHO labelled the outbreak a full-fledged pandemic. Estimates of the basic reproduction number (R0) based on the first wave of transmission suggest that the 2009 pandemic strain spreads with comparable or slightly greater efficiency among humans than seasonal influenza viruses. Data from animal models support this finding: the 2009 H1N1 strains transmit readily among ferrets and guinea pigs. The transmission phenotype of 2009 H1N1 influenza viruses is remarkable when one considers the behaviour of diverse swine isolates in human and guinea pig hosts. Although both species are susceptible to infection with swine influenza viruses of various lineages, transmission to contacts is infrequent. Thus, it appears 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 facilitate efficient human-to-human spread. In addition to these viral factors, host and environmental factors have had a clear impact on pandemic viral transmission. The observed inverse correlation between attack rate and age, for example, is most likely due to the exposure history of hosts in different age groups. Indeed, guinea pigs with prior exposure to seasonal influenza show lower rates of transmission, while vaccination of mice with classical H1N1 influenza viruses protects against disease upon challenge with the pandemic strain. The emergence of the swine-origin strain during the spring in the Northern Hemisphere was also important in shaping its epidemiology: although transmission continued throughout the summer, peak influenza activity occurred only later, during the autumn and winter months. In the guinea pig model, we have found that aerosol transmission of a 2009 pandemic strain shows a very similar dependence on humidity and temperature as a seasonal H3N2 influenza virus suggesting that, in the coming years, novel H1N1 epidemics will adopt winter-time seasonality.

Pathology Findings of Fatal 2009 Influenza A/H1N1 Viral Infections in New York City

James Gill, Office of Chief Medical Examiner

We reviewed medical records, autopsy reports, microbiologic studies, and microscopic slides of 34 people who died between May 15 and July 9, 2009. The majority of the 34 decedents (62%) were between 25-49 years of age (median 41.5 years). Tracheitis, bronchiolitis, and diffuse alveolar damage were noted in most cases. Influenza viral antigen was observed most commonly in the epithelium of the tracheobronchial tree, but also in alveolar epithelial cells and macrophages. Most were RT-PCR positive for influenza. Bacterial pneumonia was detected in 55%. Underlying medical conditions including cardiorespiratory diseases and immunosuppression were in 91% of deaths. Obesity (BMI >30) was noted in 72% of adults and adolescents. The pulmonary pathological findings in fatal disease caused by the novel pandemic influenza virus are similar to findings identified in past pandemics. Superimposed bacterial infections of the respiratory tract were common. Pre-existing obesity, cardiorespiratory diseases, and other co-morbidities also were prominent findings among the decedents.

CDC Pandemic Response: Testing Preparedness

Michael W. Shaw, Centers for Disease Control and Prevention

As the US Government primary front-line responder to infectious disease outbreaks, the Centers for Disease Control and Prevention has for many years conducted extensive pandemic response exercises in preparation for the inevitable appearance of a new, rapidly spreading influenza pandemic strain. These preparedness assumptions were put to the test over the past year as the real thing occurred and unanticipated developments required real-time reassessment and modification of response strategies. From the initial identification of the new pandemic strain by CDC in the Spring of 2009 to the roll-out of the vaccination campaign the following Fall, CDC was intimately involved in surveillance, clinical management, and infection prevention and has served as the primary source of information for the public and scientific communities here and abroad. Systems put in place prior to the pandemic proved to be invaluable as severe strains were placed on the public health system of the US. Data and viruses were shared rapidly and openly, new diagnostic assays were deployed in record time, and a new vaccine was developed, tested, and dispensed all with the cooperation of numerous government and private agencies and institutes. A history of events will be presented illustrating the rapidly evolving situation and the CDC role in this first influenza pandemic of the Twenty-First Century.

The 2009 H1N1 Pandemic - An Industry Perspective

James Matthews, Sanofi Pasteur

For much of the past five years, the WHO, Governments and Industry have focused on plans to contain the next pandemic that many thought would evolve from one of the avian H5N1 viruses that have now become endemic in most of Southeast Asia. Many of the planning scenarios predicted an epicenter in Southeast Asia with high case-fatality ratios and with some effort of early containment to slow the spread of the pandemic by employing limitations of movement, antivirals and stockpiled H5N1 vaccines. Based on clinical experience with H5N1 vaccines from the past decade, it was assumed the pandemic vaccine would likely be adjuvanted and probably require the administration of two doses, in order to provide full protection. In April 2009, the public health community was somewhat surprised, therefore, by the appearance of a novel H1N1 virus with pandemic potential, not in Southeast Asia but in North America. In this presentation, I will review the chronology of events from the time that the 2009 H1N1 virus was first identified as a pandemic threat, focusing on activities related to the development and distribution of inactivated H1N1 vaccines. The presentation will attempt to highlight how the 2009 H1N1 pandemic and the H1N1 vaccine was a departure from the avian H5N1 planning scenarios and some of the lessons we might learn in anticipation of the next pandemic.

Influenza Virus-Like Particle (VLP) as Effective and Economical Human and Animal Vaccines

Jose M. Galarza, TechnoVax, Inc.

Influenza virus-like particle (VLP) vaccines have been demonstrated to be highly immunogenic and efficacious in protecting against diverse strains of influenza virus. The flu VLP vaccines are created by the simultaneous expression of four influenza proteins, M1, M2, HA and NA which self assemble at the plasma membrane of the producing cell and are released from the cell surface as virus-like particles. VLPs are morphologically and biochemically similar to wild type virus; but do not carry virus genetic material, making these particles unable to replicate or cause infection. Electron microscopic examination of purified VLPs has shown that these structures appear identical in conformation and distribution of surface components to the wild type influenza virus. In addition, VLPs are functional in agglutinating red blood cells which demonstrates their ability to bind the sialic acid containing viral receptor. Because of the repetitive array and native conformation of the surface antigens, VLP vaccines are highly immunogenic when administered via parenteral (im, sc, id) or local mucosal routes. Production of VLP vaccines can be attained using different protein expression systems, e.g. baculovirus, continuous cell lines, and other vector systems. Given the time constraints of preparing for epidemic and pandemic pathogens as well as the large number of doses of vaccine required world wide, it is imperative that we create a better and faster strategy for vaccine creation and production. We have developed not only new production methods to increase capacity and reduce time but also a novel strategy for creating polyvalent VLP vaccines. This new method allows for the generation of particles that display on their surfaces two or more antigenically distinct influenza hemagglutinin (HA) molecules, e.g. H5 and H1. This approach would reduce manufacturing steps while increasing vaccine coverage. Immuno-electromicroscopy of polyvalent VLP have shown that both HA molecules are present on the surface of the same VLP. The influenza VLP technology provides a versatile platform not only to create and develop monovalent or polyvalent influenza vaccines, but also for large scale manufacture in cell systems which overcomes most of the limitations of the current egg-based production method. This VLP platform offers a viable new method for the production of highly immunogenic and efficacious influenza vaccines in a shorter time, larger scale and more competitive cost to attend to the human and animal influenza vaccine demands.

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