Meeting Report: Canadian Pandemic Preparedness Meeting: From Discovery to Frontlines

November 6-8, 2008
Winnipeg MB

Table of Contents

Executive Summary
Meeting Overview
Pre-Meeting Summary
Main Meeting Summary
Welcome and Opening Remarks
Session 1: Biology and Diagnosis of Influenza Virus
Session 2: Pandemic Planning Including Ethics and Legal Issues
Session 3: Transmission, Antivirals and Infection Control
Session 4: Vaccines and Immune Modulation
Closing Remarks
Evaluation of the Meeting by Participants
Appendices

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Organizing Committee
Carol Richardson, Chair	Canadian Institutes of Health Research
Earl Brown	University of Ottawa
Dominique Charron	International Development Research Centre
Michelle Gagnon	Canadian Institutes of Health Research
Michelle Hume	Canadian Institutes of Health Research
Mark Loeb	McMaster University
Anne Malo	Public Health Agency of Canada
Olivier Robledo	Canadian Institutes of Health Research
Manjeet Sethi	Canadian Food Inspection Agency
Bhagirath Singh	Canadian Institutes of Health Research
Program Subcommittee
Earl Brown, Chair	University of Ottawa
Guy Boivin	Centre hospitalier universitaire de Québec
Todd Hatchette	Queen Elizabeth II Health Science Center
Michelle Hume	Canadian Institutes of Health Research
Bryce Larke	Public Health Consultant
Allison McGeer	Mount Sinai Hospital
Christine Power	Canadian Food Inspection Agency
Carol Richardson	Canadian Institutes of Health Research
Ross Upshur	University of Toronto
Veronica von Messling	INRS-Institut Armand-Frappier
Tania Watts	University of Toronto
Tom Wong	Public Health Agency of Canada
Logistics Subcommittee
Tim Booth	Public Health Agency of Canada
Diane Christin	Canadian Institutes of Health Research
Melissa Gagnon	Public Health Agency of Canada
Michelle Hume	Canadian Institutes of Health Research
Susan Lalumière	Canadian Institutes of Health Research
Lucie Lavergne	Canadian Food Inspection Agency
Anne Malo	Public Health Agency of Canada
Carol Richardson	Canadian Institutes of Health Research
Jill Shields	Canadian Institutes of Health Research

Executive Summary

Over 150 influenza and pandemic researchers and experts attended the Canadian Pandemic Preparedness Meeting: From Discovery to Frontlines on November 6-8, 2008 in Winnipeg, Manitoba. The meeting was organized and sponsored by the Canadian Institutes of Health Research Institute of Infection and Immunity (CIHR-III), Public Health Agency of Canada (PHAC) and Canadian Food Inspection Agency (CFIA). The objectives of the meeting were to present and discuss recent research results, foster collaboration, create linkages between researchers and those who will use the knowledge generated, and to identify research needs and gaps. This report provides a summary of the meeting including a synopsis of each oral presentation along with the related research conducted or interests of all meeting participants.

An informative pre-meeting session was held for meeting participants at the Canadian Science Centre for Human and Animal Health (CSCHAH). This is a state-of-the-art laboratory with the only biosafety level 4 containment facilities in Canada. It is home to the PHAC National Microbiology Laboratory (NML) and CFIA National Centre for Foreign Animal Disease (NCFAD). NML works to identify, investigate, control and prevent infectious disease. NCFAD provides scientific and laboratory services for the rapid and accurate identification and reporting of foreign animal diseases. Participants learned about the facility and the research related to pandemic influenza that is being conducted through presentations by CSCHAH researchers.

Dr. Andreas Reis of the World Health Organization (WHO) gave the opening keynote address of the main meeting. Dr. Reis discussed ethical issues in pandemic preparedness and a guidance document on this issue that was published by WHO in 2007. Four main areas of ethical concern were outlined: distributive justice and equitable access, public health measures, obligations of and to health-care workers, international collaboration and research. Dr. Reis elaborated on these issues and described WHO recommendations to address them.

Dr. Bhagirath Singh, Scientific Director of CIHR-III then gave an overview of the Pandemic Preparedness Strategic Research Initiative (PPSRI). PPSRI was established by CIHR-III, with funds from the Government of Canada and partners, to support and promote research and build capacity in pandemic influenza preparedness. In the first phase of PPSRI, strategic research areas were identified and supported by research grants. In the second phase, researchers received grants to set up research teams and plans that will be deployed in the event of a pandemic. An essential third phase will be the dissemination of the knowledge generated. The meeting in Winnipeg is part of this third phase. Dr. Singh said that the number of influenza and pandemic researchers that had gathered for the meeting, the linkages formed and the knowledge exchanged demonstrates that the efforts by CIHR-III and partners are yielding results: Canada has a greater research capacity in this area than it did when the Initiative began in 2006.

The rest of the meeting consisted of oral presentations, roundtable discussions and two poster sessions. The oral presentations were organized into four theme areas: biology and diagnosis of influenza virus; pandemic planning including ethics and legal issues; transmission, antivirals and infection control and vaccines and immunomodulation. Each session began with a keynote address followed by three to four shorter talks. At the end of each session, a roundtable discussion took place in which participants were asked to identify research needs and gaps in the area. Two poster sessions were also held to provide an opportunity for other researchers to present and discuss their research results with meeting participants.

Dr. Adolfo García-Sastre from Mount Sinai School of Medicine gave the keynote address at the start of the session on the biology and diagnosis of influenza virus. Dr. García-Sastre and his colleagues have reconstructed the highly pathogenic 1918 influenza virus. The overall aim of the research is to understand the parts of the 1918 virus that are responsible for its virulence and ability to transmit, because the next pandemic strain of influenza might share some of the same characteristics. The knowledge will be used to predict the risks that existing animal strains of the virus pose to humans and to identify targets for prevention and treatment strategies. In the short talks that followed, participants learned about a mechanism that the influenza virus uses to inhibit cellular processes allowing it to replicate within host cells, genetic approaches to discover host genes that confer susceptibility or resistance to influenza infections, and a novel viral system to allow researchers to safely conduct studies on highly pathogenic influenza viruses.

The oral session on pandemic planning including ethics and legal issues began with a keynote address from Dr. Ross Upshur from the University of Toronto Joint Centre for Bioethics. Dr. Upshur gave an overview of ethical issues raised by public health emergencies such as an influenza outbreak. He described the new CanPREP program that he and his team have implemented. It builds on a report entitled "Stand on Guard for Thee" that provided an ethical framework for pandemic planning and preparedness. The results of the CanPREP program will aid in future emergency and pandemic planning in Canada and abroad. In the short talks, participants learned about a pilot project using focus groups to gauge opinion on public health policies, a new framework for public health ethics, and preliminary studies on the degree to which ethics research is translated into policy.

Dr. Mark Loeb from McMaster University gave the keynote address in the session on transmission, antivirals and infection control. He provided an overview of influenza transmission and described the research that he and his colleagues have undertaken to understand the natural transmission of influenza virus in the community and to determine whether immunization will reduce transmission. The team has studied several Dariusleut Hutterite colonies in Alberta. In the first year of the study, the researchers discovered that there were high rates of viral shedding among participants with and without flu-like symptoms and that the duration of shedding was highly variable. Novel influenza treatments such as the use of nitric oxide and modulators of lipid mediators of inflammation were described in the short talks, along with research on different types of influenza vaccines and their ability to prevent influenza transmission.

The session on vaccines and immunomodulation began with a keynote address by Dr. David Woodland from the Trudeau Institute. Dr. Woodland described research that he and his team have conducted to understand the maintenance of T cell memory following influenza infection and immunization and the recruitment of the memory T cells to the lungs following challenge with influenza. It is essential to understand these processes because improved vaccines against influenza will likely require the generation of robust T cell responses. Dr. Woodland has discovered that the chemokine receptor, CCR5, is needed for the early recruitment of memory T cells to the lungs following infection. In the short talks that followed, participants learned about the results of a clinical trial to assess the safety and efficacy of different pre-pandemic H5N1 influenza vaccines, novel immunization approaches to promote cytotoxic T cell responses, and the results of research examining the effectiveness of Ontario's universal immunization program.

Research needs and gaps were identified in the roundtable discussions that followed each session. Several participants indicated that a repository for influenza resources (e.g. viral strains, recombinant strains, standardized reagents, location where animal studies could be conducted, etc.) needs to be established. Also links between individuals in all areas of pandemic and influenza research must be enhanced. Ideally this would involve the creation of a centre of excellence for influenza research. Participants identified several gaps in the area of influenza and pandemic preparedness for which research is need. These include research on:

• The effects of aging and chronic diseases on influenza transmission and disease.
• Immunological factors that allow individuals to survive pandemic influenza.
• Methods to ensure that health-care workers will want to report to work during a pandemic.
• Ways to improve communication between public health officials and the media.
• Transmission of the influenza virus and how to prevent it.
• The use of combinatorial therapy to improve treatment and circumvent the development of viral resistance.
• Novel antivirals and methods to combine existing antivirals and immunomodulators.
• Ways to create better influenza vaccines, including vaccines that are cross-protective, stimulate T cell responses and/or generate mucosal immunity.
• The impact of natural infection on the immune system.

Dr. Singh closed the meeting by outlining some new initiatives related to influenza and pandemic preparedness research including the International Microbiome Consortium and the Canada-California Strategic Innovation Partnership. He thanked the meeting organizing, program and logistics committees for their efforts and participants for contributing to the meeting. Dr. Singh reminded participants that the threat of pandemic influenza is an ongoing, global issue and that it is essential to maintain the capacity that has been established and to keep the research momentum going.

The participants and meeting organizers agreed that the meeting was a tremendous success. Participants appreciated the breadth of topics and the opportunity to voice opinions in the roundtable discussions. An overwhelming majority stated the meeting provided an excellent opportunity to network and to get to know researchers in different areas.

Meeting Overview

Over 150 Canadian and international influenza and pandemic researchers and experts attended the Canadian Pandemic Preparedness Meeting: From Discovery to Frontlines on November 6-8, 2008 in Winnipeg, Manitoba. The overall goal of the meeting was to provide an opportunity for participants to present new research results, discuss ongoing research and build collaborations and linkages that will help Canada and the rest of the world prepare for the next influenza pandemic. The specific objectives were to:

• summarize the current state of participants' research in pandemic preparedness and influenza;
• enhance linkages and interactions between researchers and end-users of research findings; and
• support networking and collaboration of pandemic preparedness and influenza researchers.

The meeting was organized and sponsored by the CIHR-III, PHAC and CFIA. It included a pre-meeting session at CSCHAH. See Appendix 1 for the pre-meeting program, Appendix 2 for the main meeting agenda and Appendix 3 for a list of participants.

The meeting began with a keynote address from Dr. Andreas Reis of the WHO on ethical issues in pandemic preparedness. Oral presentations were organized into four sessions: biology and diagnosis of influenza virus; pandemic planning including ethics and legal issues; transmission, antivirals and infection control and vaccines and immunomodulation. Each session began with a keynote address followed by three to four shorter talks. See Appendix 5 for further information on the keynote speakers and their research and Appendix 6 for information on the presenters of the short talks. In addition, researchers had an opportunity to view posters and discuss research findings in a two poster sessions (Appendix 7). Additional information regarding pandemic- and influenza-related interests of the participants can be found in Appendix 8.

Pre-Meeting Summary

CSCHAH is jointly operated by the PHAC and the CFIA. Participants were welcomed to the session by Dr. Tim Booth, Director of the Viral Diseases Division of the PHAC National Microbiology Laboratory (NML), and Dr. Søren Alexandersen, Director of the CFIA National Centre for Foreign Animal Disease (NCFAD). This was followed by a series of presentations about the facility and the research related to pandemic influenza that is being conducted by researchers there. See Appendix 4 for additional information about the pre-meeting speakers and their research.

Virtual Tour of the CSCHAH
Ms. Joy Stadnichuk, NML, PHAC
The CSCHAH is home to branches of two Government of Canada agencies: PHAC's NML and CFIA's NCFAD. The agencies have extensive expertise in infectious diseases in humans and animals and work side-by-side on diagnostics and research to protect the health and economy of Canadians. Having both agencies together in one building fosters collaboration and cooperation resulting in better science and policy. The mandate of NML is to identify, investigate, control and prevent infectious disease. NCFAD provides scientific and laboratory services for the rapid and accurate identification and reporting of foreign animal diseases. The facility opened in 1999 and has 500 employees. It houses the only containment level 4 laboratories in Canada and these are used for the study of dangerous agents that usually produce very serious and untreatable disease in humans. Several precautions, including negative pressure air flow, special construction of the labs and sterilization of all air and waste that exit are in place to contain these agents. The majority of the laboratory space has biosafety level 2 and 3 laboratories. The centre has a community liaison committee consisting of representatives from neighborhood groups, community associations, professional organizations and CSCHAH. The committee was established to enhance public trust, provide information and allow public input.

Overview of pandemic research at the PHAC National Microbiology Laboratory
Dr. Tim Booth, NML, PHAC
Dr. Booth described several key research activities performed by NML that are related to seasonal and pandemic influenza. NML is part of the World Health Organization (WHO) influenza surveillance system and is the National Influenza Centre for Canada. Surveillance of influenza strains is needed to ensure that there is a close antigenic match between circulating viruses and seasonal influenza vaccines and for the early detection of pandemic influenza. Accurate surveillance also allows for effective decision making on national influenza control strategies and campaigns. The data collected contributes to FluWatch: a website that provides timely and up-to-date information on influenza activity in Canada and abroad to professionals as well as the public. NML also provides specialized reagents, training and technical support for influenza subtyping, genotyping and drug susceptibility assays. In addition to its surveillance activities, NML conducts research to help Canada prepare for pandemic influenza. The research includes understanding the pathogenesis of pandemic influenza strains, developing new technologies to improve influenza vaccines, and enhancing diagnosis of emerging influenza strains and other respiratory viruses. The reagents, expertise, research capacity and linkages that have been established by NML will be critical during the next influenza pandemic.

Canada's National Influenza Surveillance System
Dr. Nathalie Bastien, NML, PHAC
Influenza virus A evolves constantly leading to recurrent yearly influenza epidemics that cause substantial morbidity and mortality. Experts agree a future influenza pandemic is inevitable, but the timing of the next pandemic cannot be predicted. Close monitoring of circulating influenza viruses is essential to detect the appearance of new variants or novel pandemic influenza strains. Dr. Bastien described the work of the Influenza and Respiratory Virus Section (IRV) of NML, which is the WHO-designated National Influenza Center in Canada. IRV collaborates with the WHO, Centers for Disease Control and Prevention (CDC) and provincial public health laboratories and hospitals to conduct national surveillance on human influenza viruses. The IRV monitors influenza activity, describes antigenic changes in the virus and determines drug-susceptibility in the circulating strains of influenza virus in Canada. It recently participated in the WHO External Quality Assessment Programme for the detection of Influenza type A virus by polymerase chain reaction and identified all of the specimens correctly. The surveillance activity also helps in evaluating vaccine effectiveness. The activities and information generated are vital for developing influenza prevention and treatment strategies for annual epidemics, as well as for the upcoming influenza pandemic.

Reverse Engineering of Flu: Studies on the Pathogenicity of 1918 Virus
Dr. Darwyn Kobasa, NML, PHAC
The influenza pandemic of 1918 was the most devastating single outbreak of infectious disease in human history. It is estimated that 40 to 50 million people died worldwide. Dr. Kobasa and his collaborators have characterized the disease and host responses in nonhuman primates infected with the 1918 virus. The research team used reverse genetics to recreate the 1918 virus and then infected macaques in biosafety level 4 facilities. The team demonstrated that the 1918 virus causes severe illness in nonhuman primates. The lethal outcome of infection is linked to an aberrant response by the host immune system to infection that include suppressed expression of type I interferons (IFNs) and genes stimulated by type I IFNs. The research results provide an understanding of why the 1918 pandemic was so severe and help to explain the mechanisms used by highly pathogenic influenza viruses to cause disease.

Evaluation of Novel Influenza Vaccines and the Basis for Immune Protection
Dr. Gary Kobinger, NML, PHAC
The incidence of poultry-to-human transmission of the H5N1 strain of the influenza virus has increased since 2003. As well, the potential for human-to-human transmission of H5N1 has encouraged efforts to develop prevention strategies. Vaccination is currently the most effective preventative measure against influenza infections, but newer more effective vaccines are needed that can provide protection against several strains at once. Dr. Kobinger and his team are developing novel influenza vaccines, testing them in animal models and examining immune responses in order to select the best vaccine and to understand the basis of protection. Several types of vaccines against H5N1 strains have been tested including ones containing purified protein, DNA, adenovirus or inactivated virus. The vaccinated animals are challenged with the same viral strain or one that is different from the one used in the vaccine, to examine protection levels. The team's studies suggest that cross-protection against diverging strains of avian influenza (H5N1) is achievable with DNA vaccines that include optimal combinations of DNA coding for different viral antigens. The results of these studies will aid in the development of the next generation of influenza vaccines.

Overview of Pandemic Research at CFIA National Centre for Foreign Animal Disease
Dr. John Pasick, NCFAD, CFIA
Dr. Pasick summarized some of the influenza A research that is being conducted at NCFAD and other CFIA laboratories. There are four main research themes: diagnostic test development, pathogenesis, ecology and epidemiology, and vaccines and immunology. In the area of diagnostic testing, researchers generated monoclonal antibodies to several recombinant influenza proteins. The antibodies have been used for several applications including the development of an H5-specific competitive ELISA. Aquatic and nonaquatic avian cell lines have also been developed that are being used to isolate and characterize avian viruses including influenza. In another project, a microsphere immunoassay has been developed to detect the presence of anti-influenza antibodies in biological samples. In the area of pathogenesis, Dr. Pasick and his collaborators have studied the effect of highly pathogenic H5N1 avian influenza on wild Canada geese in the laboratory. The goal is to determine the effect that H5N1 would have on waterfowl if it were to arrive in Canada. Infected adult geese did not develop clinical signs or infection, but naïve juveniles were markedly susceptible and infection was detected in several tissues. Therefore naive juveniles are suitable for surveillance efforts. In the area of ecology and epidemiology, a national surveillance program for influenza A in wild birds has been implemented. The information acquired and research capacity that is built by this program is useful for several reasons including the ability to conduct a retrospective analysis in response to disease outbreaks. Dr. Pasick concluded by describing the Canadian Notifiable Avian Influenza Surveillance System that is being developed by CFIA in collaboration with provincial and territorial governments and poultry industry representatives. The system is designed to meet the guidelines of the World Organisation for Animal Health (OIE) and new trade agreements from the European Union that take effect January 2009.

Vaccination Strategies for Avian Influenza
Dr. Shawn Babiuk, NCFAD, CFIA
Most avian influenza subtypes cause mild or asymptomatic infections in chickens. However, low pathogenic H5 or H7 avian influenza viral strains can evolve within chickens to become highly pathogenic. The highly pathogenic strains of avian influenza cause rapid death in chickens, and some strains can infect and kill humans. Methods to eradicate highly pathogenic strains of avian influenza from birds, such as killing infected flocks, have failed in certain regions. Vaccination would be an alternative approach to limit the impact of avian influenza. Current killed influenza vaccines are effective in preventing death in chickens from avian influenza, but do not prevent viral shedding and are not cross-protective. Several experimental vaccines are being developed by multiple independent groups including Dr. Babiuk's team. The characteristics of an ideal vaccine are that it should be easy to administer (e.g. via drinking water), inexpensive, safe, provide protection against both H5 and H7 pathogenic strains, prevent viral shedding and one should be able to distinguish vaccinated animals from those that have natural infections. Development of such a vaccine would help to improve both avian health and possibly prevent an influenza pandemic.

Review of the 1918 Pandemic Influenza Animal Experiments at National Centre for Foreign Animal Disease
Dr. Hana Weingartl, NCFAD, CFIA
Wild waterfowl are the natural reservoir of influenza A viruses. Influenza viruses occasionally acquire the ability to cross species to infect pigs or humans. For example, it appears that a single amino acid change in the hemaggluttin molecule of 1918 pandemic strain of influenza virus allowed it to infect humans. Pandemics can result if the virus is highly pathogenic and acquires the ability to be transmitted from human to human. Dr. Weingartl and her collaborators have conducted a series of experiments examining the ability of the 1918 virus to infect and cause disease in both pigs and birds. The team discovered that the 1918 virus was able to infect and cause disease in pigs, although the clinical symptoms were less severe than historical reports of hog flu dating from 1918. The results lend support to the hypothesis that the 1918 pandemic influenza virus is an ancestor of both human H1N1 viruses and classical swine H1N1 viruses. In other experiments, all of the birds inoculated with the 1918 pandemic influenza virus survived and did not show clinical signs of disease, although infected ducks did shed the virus. Dr. Weingartl hypothesizes that the 1918 influenza virus originated in birds, spread to humans in a still unknown way and then to pigs, which played a role in maintaining and spreading the human pandemic influenza strain. The better understanding of the biology of the 1918 virus that has been gained by these experiments will allow us to recognize the potential risk of circulating animal viruses to initiate pandemics and will provide novel targets for therapeutic and prophylactic intervention.

Main Meeting Summary

Welcome and Opening Remarks

Chair: Dr. Earl Brown, University of Ottawa
As Chair of the meeting in Winnipeg, Dr. Brown welcomed participants and gave an overview of the program.

Dr. Bhagirath Singh, CIHR Institute of Infection and Immunity
Dr. Singh extended a warm welcome to all meeting participants on behalf of the meeting sponsors; CIHR, PHAC and CFIA. He said that the number of participants and the outcomes of the research to be presented at the meeting in Winnipeg demonstrate that coordinated efforts to build research capacity in the area of pandemic preparedness and influenza are yielding results.

Efforts to support and promote research for pandemic influenza preparedness began with the Influenza Research Priorities Workshop that was held in Ottawa in 2005 and was jointly sponsored by PHAC and the CIHR Institute of Infection and Immunity (CIHR-III). Based on recommendations from the workshop, and with funds from the Government of Canada and partners, CIHR-III established the Pandemic Preparedness Strategic Research Initiative (PPSRI). The meeting in Winnipeg is part of the PPSRI and provides an ideal opportunity to inform colleagues, bring disparate groups together and develop collaborations. Dr. Singh conveyed best wishes for a productive meeting from Dr. Alain Beaudet, President of CIHR, and Dr. Arlene King, Director General of PHAC Centre for Immunization and Respiratory Infectious Diseases.

Dr. Singh concluded by stating that the flu season was approaching and that the efforts of the participants will be important for preventing and treating seasonal influenza, pandemic planning, and preparing for respiratory infections in general.

Ethical Issues in Pandemic Preparedness: Global Guidance and National Planning
Dr. Andreas Reis, World Health Organization
Dr. Reis provided an overview of the work that the WHO has done in addressing ethical issues in pandemic preparedness and response. In 2007, the WHO published a guidance document entitled "Ethical considerations in developing a public health response to pandemic influenza". The report focuses on four main areas of ethical concern: distributive justice and equitable access, public health measures, obligations of and to health-care workers, international collaboration and research.

Distributive justice and equitable access involves trying to find a balance between allocating scarce resources such as vaccines, antivirals and health care to produce the most benefit to society versus giving priority to those at most risk of dying. For example, should one save the most lives, the most life years by treating children first, or give priority to health-care workers and people between the ages of 13 to 40 years of age? Priority setting must respect human rights, involve stakeholder and public engagement and include appropriate communication strategies.

The second area, public health, involves issues of isolation, quarantine and social distancing in which a tension exists between the interests of society and the freedom of the individual. Public health decisions should be made in an open, fair and legitimate manner and involve community participation to enhance trust. Governments should explicitly define who has the power and how decisions will be made. Measures should be voluntary (if possible), personal information should be kept confidential, penalties for noncompliance should be proportional and those quarantined should be cared for.

The third area, obligations of and to health-care workers, involves questions such as: Do health-care workers have a duty to care in a pandemic? Should they receive priority for treatment or vaccination? How and by whom should obligations be formulated and enforced? To address these questions, the WHO recommends that governments should ensure that risks to health-care workers are minimized, that they should receive adequate education and information and that a benefits system be developed. These measures will promote compliance of health-care workers. Policies should be developed jointly before a pandemic occurs.

The final area discussed by Dr. Reis was international collaboration and research. Governments must determine how to balance their duties to their own population versus those in other countries. Ethical issues in research during outbreaks also need to be considered.

Dr. Reis outlined several recent and planned initiatives by the WHO involving ethics and pandemic planning. These include a Canadian Stakeholder Forum organized by the University of Toronto Joint Centre for Bioethics in January 2009. Dr. Reis concluded his keynote address by reminding participants that new infectious diseases will continue to emerge. It is critical to develop national and global capacity to detect and respond effectively in a way that respects ethics and human rights standards.

Canadian Research Agenda for Pandemic Preparedness
Dr. Singh gave an overview of PPSRI. In May 2006, CIHR-III established PPSRI with the support of $21.5 million over five years from the Government of Canada. CIHR-III then moved quickly to establish partnerships with PHAC and CFIA and others to coordinate national strategies and increase funding to $41 million.

The first phase of PPSRI involved both building research capacity and stimulating research in strategic priority areas that were identified by the PPSRI Task Group in consultation with stakeholders. The strategic areas are: vaccines and immunization programs, biology of the virus, prevention and treatment and ethics, legal and social contract. PPSRI has funded grants in all of these areas. In the second phase, preparations are being made for outbreak research via Catalyst grant funding opportunities. An important component is knowledge translation, which is emphasized in the third phase via targeted research funding opportunities and meetings. It is critical to communicate new research results to health-care professionals and policy makers and to the general public via the media.

Dr. Singh closed by saying that he looked forward to the meeting and to hearing about the progress that has been made in influenza and pandemic research. He encouraged those present to keep the momentum that had been generated and to use the meeting as an opportunity to build bridges and create linkages.

Session 1: Biology and Diagnosis of Influenza Virus

Co-Chairs: Dr. Earl Brown, University of Ottawa
Dr. Todd Hatchette, Queen Elizabeth II Health Science Center

Keynote Address: Virulence and Transmission of the 1918 Influenza Virus
Dr. Adolfo García-Sastre, Mount Sinai School of Medicine
The Spanish influenza pandemic of 1918 resulted in the death of 40 million people worldwide. Dr. García-Sastre and his collaborators have reconstructed the 1918 influenza virus based on sequence information obtained from viral genetic material taken from bodies of individuals who died in 1918 and from stored pathological specimens. The overall aim of the research is to understand the genetic determinants of the 1918 virus that were responsible for its virulence and transmission in 1918, because the researchers hypothesize that the future pandemic strain of influenza might share some of the same characteristics. The knowledge can be used to predict the risks that existing animal strains of the virus pose to humans and to identify targets for prevention and treatment strategies.

Dr. García-Sastre and his collaborators have discovered that the 1918 virus has an enhanced ability to replicate in animals and in cultured human cells and that a component of the virus, hemagglutinin (HA), is critical for virulence. Also, a single amino acid change in HA changes receptor specificity and determines transmission in ferrets. The 1918 virus induces exaggerated immune (cytokine) responses in hosts suggesting that part of the pathogenesis might be the result of an excessive host response. Currently available antivirals such as M2 inhibitors and neuraminidase inhibitors prevent death of animals infected with the 1918 virus providing they are administered 24 hours after infection. In addition, immunization against H1N1 protects against the 1918 strain.

Influenza A Virus Infection Activates Phosphatidylinositol 3-kinase (PI3K)/Akt Signalling Pathway
Dr. Yan Zhou, Vaccine and Infectious Disease Organization (VIDO)
Viruses have evolved mechanisms to inhibit cellular processes that would normally help to clear the infection. Dr. Zhou has discovered that the influenza viral protein NS1 activates the PI3K/AKT signaling pathway by directly binding to the p85 subunit of PI3-kinase. One of the roles of this signaling pathway is to inhibit cell death or apoptosis. Dr. Zhou postulates that the lack of host cell death allows the virus to replicate. Dr. Zhou has identified the region of NS1 that interacts with p85 and has determined that virus carrying mutations in this region of NS1 are less able to replicate. The interaction between NS1 and p85 is a potential target for novel anti-influenza drugs.

A New Model of Highly Pathogenic Influenza Virus Infection
Dr. Silvia Vidal, McGill University
During infectious disease outbreaks, some humans die from infection while others survive. Part of this difference is due to variations in innate immune responses of the human host that are caused by genetic differences. Mice are an excellent animal model to study the gene variants that confer protection or susceptibility to infection because several genetically different strains of mice exist and the mouse genome is well characterized. To examine genetic determinants of host susceptibility, Dr. Vidal has infected a number of inbred strains of mice with a mouse-adapted influenza virus that contains pathogenic mutations from highly virulent H5N1 subtypes. The A/J mouse strain had more severe pathological symptoms and was more likely to die. Dr. Vidal has determined that the genes responsible for this susceptibility are located within 12% of the mouse genome. Future work will involve narrowing this region down further to identify the specific genes that are responsible for host susceptibility. Ultimately, this work will help to elucidate the genetic variations that explain why some individuals die and some survive pandemic influenza, and perhaps lead to tailored therapies or treatment regimes.

Development and Characterization of a Safe and Efficient Avian Influenza H5N1 Virus Entry System for Virological and Antiviral Studies
Dr. Xiaojian Yao, University of Manitoba
The H5N1 subtype of avian influenza virus has already caused over 300 deaths in humans, and it is possible that it might acquire the ability to be transmitted from human to human leading to the next influenza pandemic. Therefore, it is essential to develop new antiviral drugs against H5N1 and to understand the biology of the subtype. The requirement for high-level biosafety facilities, however, has limited the number of studies that have been conducted. Dr. Yao has devised a novel and safe method to study H5N1 virus entry in the normal laboratory setting. In his viral entry system, he expressed H5N1 genes [hemagglutinin (HA), neuraminidase (NA) and M2 ion channel] in a lentiviral vector system. He modified the hemagglutinin gene so that trypsin would be needed to cleave HA to allow entry of the virus into cells. He has used this vector system to create a safe and high-throughput method to screen for anti-influenza drugs. Also, this system will allow researchers to examine the ability of envelop proteins derived from clinically-isolated viruses to target human airway cells.

Roundtable Discussion—Session 1
Participants were asked to identify research needs and gaps in the discussion that following the session. The following points were made:

• One participant mentioned that research on diagnostics, including point-of-care tests, does not seem to be a focus of CIHR funding; however, another participant mentioned that researchers at McMaster University had received a PPSRI grant to develop influenza diagnostics.
• Rapid sequencing is now performed at NML and BC Centre for Disease Control (BCCDC), but the infrastructure must be enhanced.
• Influenza might not be the only pandemic, therefore, we should support research on respiratory viruses in general, including determinants of transmission and pathways in the host respiratory tract.
• During infection there is a virus/host interaction and in order to fight infection it will be important to consider human cellular processes that could be targeted.
• Links must be established between virologists and bacteriologists to get a more complete understanding of pandemic influenza. For example, it has been postulated that many of the deaths associated with the influenza pandemic of 1918 were actually caused by bacterial infections.
• One participant suggested that there should be a repository for influenza resources (e.g. viral strains, recombinant strains, location where animal studies could be conducted, etc.)
• Ideally, a centre of excellence for influenza research should be established. Information about animal models and reagents could be shared. As well, a coordinated plan for pandemic research could be formulated before the next pandemic.
• Our population is aging, and we have no good animal models. We need to understand the impact of influenza on non-communicable diseases such as stroke and myocardial infarction. Also, current influenza vaccines do not work well in the elderly—we need to develop better vaccines for this population.
• We need an understanding of the immunological forces that allow many individuals to survive pandemic influenza—in other words, what distinguishes those who live from those who die?

Session 2: Pandemic Planning Including Ethics and Legal Issues

Chair: Dr. Ross Upshur, University of Toronto Joint Centre for Bioethics

Keynote Address: Ethical Challenges in Pandemic Preparedness (The CanPREP Project)
Dr. Ross Upshur, University of Toronto
Until relatively recently, ethical issues related to infectious diseases were largely neglected. This is due in part to the complexity of infectious diseases, which require understanding of a wide-range of disciplines. Also, the nature of infectious disease means that ethical issues must be considered at several levels from personal through to global health. Dr. Upshur and his team have focused on the ethical issues raised by public health emergencies such as an influenza outbreak. Their work started with a study of the ethical problems faced by the SARS crisis in 2003. More recently, they produced a report entitled "Stand on Guard for Thee" that provides an ethical framework for pandemic planning and preparedness. The CanPREP Program will build on this foundation. In one phase of the program, nationwide public perspectives will be solicited on the four ethical challenges faced during a pandemic: health workers' duty to care; restrictive measures to protect the public good; priority setting and allocation of scarce resources; and global governance. This perspective, along with other information collected will be used to develop and refine the "Stand on Guard for Thee" ethical framework. Innovative methods including social networking will be used to gather information. The new knowledge will aid in future emergency and pandemic planning in Canada and abroad.

Should Canada Create a National Antiviral Stockpile for Prophylaxis in the Event of an Influenza Pandemic? – The Criteria System as a Tool for Deliberative Discussion
Dr. Caroline Alfieri, Centre hospitalier universitaire Sainte-Justine and Department of Microbiology and Immunology, University of Montreal
As part of Canada's preparedness strategy for an influenza pandemic, a national antiviral stockpile consisting of 55 million doses of neuraminidase inhibitors for treatment of influenza has been amassed. There is currently no stockpile, however, for prevention of influenza infection. Dr. Alfieri and colleagues undertook a pilot study to determine whether focus group consultations would be useful in determining whether this type of antiviral stockpile should be created, and if so, which groups should be priority recipients. Health-care workers were asked to participate because they would be immediately impacted by decisions regarding antiviral use. Focus group consultations with health-care workers in Montreal and Toronto were conducted. Overall, the findings suggest that while most participants expressed preference in favour of establishing an antiviral stockpile for prevention, their enthusiasm was tempered by concerns for safety and efficacy, and by associated guilt should antivirals be offered to them but not to their family members. The study demonstrated the effectiveness of focus group consultation to obtain input on policy issues from targeted groups. The results attest to the importance of instituting communication channels and special interactive/education sessions before decision-makers enact policy on the creation of a separate antiviral stockpile for prevention.

Some Foundational Reflections for an Ethic of Public Health
Dr. Nuala Kenny, Dalhousie University
Health care, with its focus on individual patient benefits, has dominated the policy agenda for the past fifty years, while public health and public health ethics have been neglected. An influenza pandemic, however, will have an impact upon virtually every aspect of society. Underlying the scientific and heath policy challenges are important ethical issues of justice, care, and protection of the public. The fear, uncertainty, and substantial risks inherent in pandemics raise these ethical concerns to a high level not only for individuals but also for societies. Dr Kenny stated that pandemic planning work regarding these issues has relied on individual bioethical concepts with insufficient attention to communal values. To remedy this situation, she and her colleagues are developing a robust, coherent and meaningful public health ethics document for Canada that will serve in times of disaster response. It will be rooted in sound values and principles such as relational autonomy, social justice, and the public good. To date, the group has made progress in laying out the inadequacy of established approaches and has identified and developed some new, relational, substantive foundations for public health ethics. The group is also analyzing the legal implications of the ethical decision making framework for pandemic planning, and methods to best involve the general public in various aspects of the ethical decision-making framework.

Ethics of Pandemic Preparedness: From Discovery to Frontlines
Dr. Jaro Kotalik, Lakehead University
Dr. Kotalik presented some preliminary data from a study he has conducted to determine whether ethics research results and recommendations are actually put into practice. In other words, whether results of ethics research is taken from discovery to the frontlines. He used as an example, a report entitled "Stand on Guard for Thee" published by the Influenza Pandemic Working Group at the University of Toronto Joint Centre for Bioethics, which contains a 15-point ethical guide for pandemic planning. Indeed, the framework has been incorporated into the Ontario Health Plan for an Influenza Pandemic. In contrast, a monthly newsletter entitled "The Pandemic Planner" published by the Ontario Ministry of Health and Long-term Care made no reference to ethical issues between September 2007 and September 2008 except for one reference to precautionary principles which is not mentioned in "Stand on Guard for Thee". Dr. Kotalik also noted that the ethical framework for the Ontario plan requires that the decision-making process ought to be inclusive. However, the plan itself provides no opportunities for stakeholders to be engaged in the decision-making process, and thus the inclusivity is lacking. Dr. Kotalik concluded that it can be difficult to translate complex ethical values into action, but he made several suggestions to enhance knowledge translation. These include: creating opportunities for ethicists to talk to people involved in pandemic planning, incorporating ethics programs in all pandemic training programs and ongoing monitoring and evaluating pandemic planning from an ethical perspective. These activities have a potential to enhance the incorporation of results of ethics research into pandemic planning.

Roundtable Discussion—Session 2
The following research needs and gaps were identified in the discussion that followed the session:

• One of the most difficult issues in a pandemic is that of individual autonomy as it relates to health-care workers. We need to develop ways to ensure that health-care workers will want to report to work. One way to address this issue is to explore the role of triage in acute care settings. In addition, ethical issues such as those presented should be part of the training and recruitment of health-care workers.
• There is a risk communication gap between public health officials and the media. Part of the problem is the nature of media stories, which emphasize crisis or the plight of the "little man". Solitary conversations and serious reflection with the media and ordinary Canadians is needed.
• Public health ethics that employs a utilitarian approach in which policies are put in place to do the greatest amount of good for the most people will not work well in the event of a pandemic. Health-care ethics will also have to be considered.
• In bioethics, there are two kinds of research: one that focuses on what is happening and another that focuses on what ought to be happening. The latter helps to develop a common mind, which is important in the prepandemic period.
• In addition to education and information sessions for health-care workers, the public also needs information to better prepare for a pandemic.
• We need a new conversation about the interface between the public and physicians.

Session 3: Transmission, Antivirals and Infection Control

Co-Chairs: Dr. Bryce Larke, Public Health Consultant
Dr. Guy Boivin, Centre hospitalier universitaire de Québec

Keynote Address: Influenza Transmission: An Epidemiologic Perspective
Dr. Mark Loeb, McMaster University
Dr. Loeb gave an overview of the epidemiology of influenza transmission, and reviewed previous limited studies that have attempted to examine the natural course of influenza infection in humans. The symptoms of influenza are reported to last approximately eight days, and a proportion of individuals shed the virus for several days prior to the onset of symptoms. To better understand the natural history of viral shedding and human transmission, Dr. Loeb and his colleagues have been studying several Dariusleut Hutterite colonies in the David Thompson Health Region in Alberta. 397 participants were enrolled during the 2007/08 influenza season. The researchers discovered that there were high rates of viral shedding among both symptomatic and asymptomatic participants and that the duration of shedding was highly variable. Since the Hutterites are pig farmers, there is also an opportunity to assess pig reservoirs of influenza virus and pig-to-human viral transmission. Last year, field tests were conducted to assess the logistics of sending specimens for analysis.

In September 2008, the researchers began an ambitious program to determine whether influenza immunization will protect other members of the community, particularly the elderly, from influenza infection. Sixty colonies in different health regions are being randomized for the trial. Primary outcomes of laboratory-confirmed influenza infection and secondary outcomes, such as influenza-like illnesses, will be monitored over a 2.5 year period. The results from these studies will provide a better understanding of human-to-human as well as human/animal influenza transmission, and the role of immunization in preventing transmission.

Dr. Loeb also described feasibility studies to assess whether there is a difference in the incidence of influenza infections in nurses who wear either surgical masks or fit-tested N95 masks when treating patients with febrile respiratory illnesses. The studies are ongoing, however, and it is too early to draw any conclusions regarding mask use and the prevention of influenza transmission.

Inhalational Delivery of Nitric Oxide Gas Reduces Infectivity of Influenza A and Highly Pathogenic Avian Influenza
Dr. Chris Miller, University of British Columbia
Dr. Miller presented evidence to show that nitric oxide is a broad-spectrum antimicrobial agent that could be used to either prevent disease transmission or improve clinical outcome in a pandemic. Nitric oxide is produced by the body and acts as a signaling molecule in many biological processes. It has antimicrobial properties, does not seem to damage host cells and has a short-half life. It is currently used as a vasodilator in neonatal medicine and in early research trials to treat patients with cystic fibrosis. Dr. Miller showed that nitric oxide reduced influenza infection of cells in culture. Nitric oxide also appeared to return temperatures and clinical symptoms to normal in a bovine viral respiratory disease study. The mechanism of action of the antiviral properties of nitric oxide is unclear, but nitric oxide might prevent viral entry into cells or reduce viral replication. Human studies examining the effect of nitric oxide on influenza infection and treatment have not yet been performed. The preliminary results that Dr. Miller presented, however, suggest that nitric oxide has the potential to be an important antiviral agent during a pandemic.

Role of the Lipid Mediators of Inflammation in a Mouse Model of Influenza Virus Infection
Dr. Louis Flamand, Université Laval (for Dr. Pierre Borgeat, Université Laval)
To counter influenza infection, the body releases a number of compounds that stimulate our immune system. These compounds are usually beneficial, but sometimes cause an exaggerated response that contributes to the pathology seen during infection. Dr. Borgeat and Dr. Flamand are focusing on a group of these compounds called "lipid mediators of inflammation". In preliminary experiments, the team discovered that three different classes of lipid mediators are elevated in the lungs of mice infected with influenza. Of the lipid mediators measured, LTB4 was most strongly increased (more than 10 fold). Next, the team plans to assess whether agonists or antagonists of the mediators will reduce inflammation, morbidity and mortality in severe influenza infections. The advantage of this approach is that the agonists and antagonists are already used as drugs or are in phase II and phase III clinical trials. These studies will provide important information that could rapidly lead to improved treatments of influenza using already available drugs.

Efficacy of Vaccines in Blocking Inter-host Transmission of Influenza Virus
Dr. Anice Lowen, Mount Sinai School of Medicine
Interventions aimed at preventing viral transmission, as opposed to specifically reducing morbidity, have the potential to effectively control influenza in all age groups, thereby reducing the burden of influenza illness. Dr. Lowen has examined the efficacy of vaccination in blocking transmission of human H3N2 subtype influenza viruses between guinea pigs. She found that previous infection through a natural route prevented transmission of the influenza virus to or from previously infected animals. Vaccination with a whole inactivated influenza vaccine, in contrast, did not prevent guinea pigs from becoming infected upon viral challenge, but did reduce the number of secondary transmission events from vaccinated animals to naive cage-mates. Vaccination with an NS1 modified live attenuated influenza vaccine created sterilizing immunity against challenge by intranasal inoculation or contact exposure. Overall, the results suggest that the efficiency of transmission is a valuable read-out when evaluating vaccine efficacy and that live attenuated influenza vaccines may be more useful in preventing influenza transmission.

Roundtable Discussion—Session 3
The following research needs and gaps were identified in the discussion that followed the session:

• Central repositories are needed for standardized reagents and viruses that can be accessed by researchers.
• More research is needed on person-to-person transmission, preventing transmission, correlating transmission with viral shedding and the role of preexisting immunity.
• Most of the interventions that have been presented at the meeting involve a single modality. Combinatorial therapy is needed to improve treatment and circumvent the development of viral resistance. More antivirals are needed, along with studies to examine combination therapies with existing antivirals and immunomodulators.
• In the Hutterite study, it is important to take into consideration contact in the community—need a randomized cohort with large enough numbers.
• Influenza vaccination rates are up in many communities, but mortality and serious complications due to influenza are seen in a proportion of the vaccinated elderly population.
• The estimates of effectiveness of the healthy vaccinee model have been exaggerated. We need to have better vaccines for those at high risk.
• All members of a Hutterite colony eat in a communal setting. This is different from the usual one to four contacts in most Canadian households. Therefore, if no effect of vaccination is observed in the Hutterite study, it is possible that vaccination would still be useful in a setting where there are fewer close contacts.
• The International Consortium on Anti-Virals could help in choosing the best models to develop NO further and cooperation would allow for comparisons to be made with other antivirals.

Session 4: Vaccines and Immune Modulation

Co-Chairs: Dr. Veronika von Messling, INRS-Institut Armand-Frappier
Dr. Allison McGeer, Mount Sinai Hospital

Keynote Address: Regulation of T Cell Immunity in the Lung
Dr. David Woodland, Trudeau Institute
It is essential to develop better influenza vaccines, because the ones in current use are suboptimal: they generate relatively weak immunity and must be reformulated every year. Dr. Woodland stated that improved vaccines will have components that generate robust T cell responses. To develop these vaccines, a detailed knowledge of T cell responses to influenza including T cell memory is needed. Dr. Woodland presented results from a series of experiments in which he examined the recruitment of memory CD8 T cells into the lung following influenza infection. There is an early and a late phase of recruitment. In the early phase (2-7 days), non-dividing, effector memory CD8 T cells that are not antigen specific are recruited. In the late phase (4-14 days), proliferating, antigen-specific, central memory CD8 T cells are recruited. Dr. Woodland has used knockout mice to examine the role of chemokines in the early phase. CCR5-deficient mice, unlike CXCR3-deficient mice, showed a profound defect in early memory CD8 T cell recruitment. Thus, CCR5 plays a major role in the recruitment of memory CD8 T cells. Rapid recruitment of memory CD8 T cells was correlated with a significant decrease of virus titers within the lung airways.

There are several implications from these results and other data presented. Cross-reactive T cells are able to mediate potent control of secondary influenza virus infections. Effective cellular immunity depends on a rapid mucosal effector memory T cell response. Contrary to current dogma, influenza virus vaccines need to be developed that promote (or refresh) long-lasting mucosal effector memory T cells.

Safety and Cross-reactive Immunogenicity of Two H5N1 A/Indonesia/5/2005 (clade 2.1) AS03-Adjuvanted Prepandemic Candidate Influenza Vaccines. A Phase I/II Clinical Trial
Dr. Joanne Langley, Canadian Centre for Vaccinology
Prepandemic H5N1 vaccines are being developed and clinically tested so that they are ready to be used in the event of a pandemic alert. The vaccines should be antigen-sparing, have an acceptable safety profile and offer cross-reactive immunity to non-vaccine strains. Most clinical studies have evaluated clade 1 strains which infected humans in 2004-2005, while clade 2 strains have infected humans since 2005. Dr. Langley and her colleagues have evaluated two H5N1 vaccine candidates made with a clade 2.1 strain. The vaccine candidates, produced by GSK at two sites (Dresden [D], Quebec [Q]) by two distinct processes, were made with A/Indonesia/05/2005 (clade 2.1) antigens. Adults were vaccinated twice, 21 days apart, with hemagglutinin (HA) with an oil-in-water emulsion-based Adjuvant System (AS03) or with antigen alone. Although, injection site pain was more frequent in the AS03-adjuvanted vaccine groups, redness and swelling occurred in less than 5% of subjects. Importantly, compliance with the two-dose schedule was as high in all groups indicating excellent vaccine acceptance. The AS03-adjuvanted A/Indonesia/05/2005 vaccines were markedly more immunogenic against the vaccine strain and a Clade 1 strain compared to the un-adjuvanted vaccine, and no safety concerns were identified. Further analysis is planned, but the results to date suggest that the adjuvanted vaccines are safe and immunogenic.

Enhancing CD8 T Cell Immunity to Influenza Virus
Dr. Theo Moraes, University of Toronto
Dr. Moraes described research he has conducted in the laboratory of Dr. Tania Watts. The overall goal of the research is to study T cell immune responses and define what CD8 T cell characteristics are relevant for protective immunity to influenza. Ultimately this would lead to vaccines that generate robust, long-term, cross-protective CD8 T cell responses. To achieve this goal, the researchers have created an adenoviral vector vaccine containing DNA coding for the nucleoprotein of the influenza virus along with the CD8 T cell costimulatory molecule 4-1BBL. When the vaccine was administered intranasally to mice, it enhanced the generation of NP-specific CD8 T cells in the lung, spleen and lymph nodes that were observed even six months after immunization. The response, however, was not significantly different from an adenoviral vector vaccine containing DNA coding for NP alone when high doses of the vaccine were used. At lower vaccine doses; however, immunization with NP and 4-1BBL offered superior protection. Thus, the addition of DNA coding for the costimulatory molecule allows for dose sparing of the antigen, which is important for both maximizing the number of doses that can be administered to a population and also for minimizing potential toxicity. In addition, the induction of CD8 immune responses offers the possibility of cross-protective immunity to multiple strains of influenza, which is relevant to both pandemic and epidemic viruses.

Evaluating Ontario's Universal Influenza Immunization Program
Dr. Jeff Kwong, Institute for Clinical Evaluative Sciences
In 2000, Ontario began the world's first large-scale universal influenza immunization program
(UIIP) to provide free influenza vaccines for the entire population aged 6 months or older. Dr. Kwong and his research team evaluated Ontario's UIIP in relation to targeted programs that exist in other provinces in Canada. While vaccination rates increased across Canada from 1996 to 2005, there was a greater increase for those under 65 years of age in Ontario. Introduction of Ontario's UIIP was associated with greater decreases in influenza-associated mortality and health-care use (hospitalizations, emergency department use, and visits to doctors' offices) in the overall population compared to other provinces. This effect was driven by younger age groups. No differences in health-care outcomes were observed in the elderly despite greater increases in vaccination rates in other provinces. These results, showing a positive effect of UIIP, will help policy-makers make informed decisions about influenza vaccination program strategies.

Roundtable Discussion—Session 4
The following research needs and gaps were identified in the discussion that followed the session:

• There needs to be more emphasis on influenza vaccines that stimulate T cells.
• Several groups are working on vaccines that stimulate innate responses, but these do not appear to be particularly useful against influenza. Natural killer cells; however, can modulate the responses by T cells.
• To combat influenza, T cells must be recruited to mucosal sites. It is not known what prevents the recruitment of central memory T cells to these sites.
• It would be useful for researchers in this area to have all of the knowledge that has been generated compiled, so that next steps could be planned.
• New methods are needed to generate mucosal immunity. It is not easy to get memory cells that are recruited to the lungs with systemic vaccination.
• It appears that older humans have some immunity to H5N1 because this strain has adversely affected more children to date, but experiments need to be done to show this.
• Studies are needed to assess the impact of natural infection on the immune system. It might be more beneficial for children to get influenza naturally when they are young so that they will be protected in old age instead of generating weak immune responses via vaccination when they are young.
• It would be useful to develop a universal vaccine that does not need to be reformulated every year, but the T cell memory that is required does not seem to be durable. Therefore, it might be necessary to boost every year with the same vaccine.

Poster Session
Over sixty posters were presented in two lively sessions that were held during the afternoon on the first day of the meeting. Posters were organized into the four meeting theme areas: biology and diagnosis of influenza virus; pandemic planning including ethics and legal issues; transmission, antivirals and infection control and vaccines and immunomodulation. A list of presenters along with their poster titles is found in Appendix 7.

Closing Remarks

Dr. Bhagirath Singh, CIHR Institute of Infection and Immunity
Dr. Singh thanked participants for coming to the meeting and contributing to the sessions. He said he was impressed with the number of participants and the breadth of expertise.

Emerging pathogens are one of the priorities of the Institute, and it is essential to maintain capacity in this area to serve the country. There are several new initiatives that CIHR is involved with that relate to influenza research. One is the International Human Microbiome Consortium that was established in October 2008. Another is the Canada-California Strategic Innovation Partnership that has infectious disease as one of its theme areas. In terms of biobanks for storing samples, NML has the capacity and has stored samples from other flu outbreaks.

Dr. Singh then extended his thanks to Ms. Carol Richardson and Ms. Michelle Hume for their efforts in organizing the meeting in Winnipeg. He thanked Dr. Mark Loeb for his work as Chair of the PPSRI Task Force. He also thanked Dr. Earl Brown for chairing the Meeting Programme Committee and Ms. Jill Shields for her assistance on the Meeting Logistics Committee. He also acknowledged CIHR's funding partners PHAC and CFIA for helping to support the event.

Dr. Singh closed by reminding participants that the threat of pandemic influenza is an ongoing, global issue. Canada is better prepared to face an influenza pandemic now in comparison with three to four years ago. This enhanced capacity is due in large part to the efforts of meeting participants and the activities of the PPSRI. It is essential to maintain the capacity that has been established and to keep the research momentum going.

Evaluation of the Meeting by Participants

The participants and organizing committee agreed that the meeting was a success. Participants appreciated the breadth of topics and the dynamic nature of the roundtable discussions. Participants felt that the meeting gave them a good picture of the varied research activities of Canadian researchers and also enjoyed the presentations from the international participants. An overwhelming majority stated that they appreciated the opportunity to get to network and get to know researchers in different areas. Most said that they would recommend the meeting to others if another meeting of the same type were held in the future. Many also enjoyed the pre-meeting session and the opportunity to visit CSCHAH. Topics that participants said should be either enhanced or incorporated into a future meeting included: public health and pandemic planning, diagnostics, novel vaccine technologies, reservoir (swine/bird) epidemiology and mathematical modeling. See Appendix 9 for a summary of responses to a questionnaire soliciting feedback on the meeting from participants.

Appendices

Appendix 1: Pre-Meeting Program [ HTML | PDF (53 KB) | Help ]
Appendix 2: Meeting Agenda [ HTML | PDF (65 KB) | Help ]
Appendix 3: Participant List [ HTML | PDF (95 KB) | Help ]
Appendix 4: Pre-Meeting Speaker Abstracts [ HTML | PDF (78 KB) | Help ]
Appendix 5: Keynote Speaker Biosketches and Abstracts [ HTML | PDF (96 KB) | Help ]
Appendix 6: Short Talk Speaker Abstracts [ HTML | PDF (130 KB) | Help ]
Appendix 7: Poster Index by Theme Area [ HTML | PDF (88 KB) | Help ]
Appendix 8: Participants' Pandemic-Related Work [ HTML | PDF (582 KB) | Help ]
Appendix 9: Summary of Evaluation of Meeting by Participants [ HTML | PDF (88 KB) | Help ]