Pandemic Preparedness Strategic Research Initiative – Report on Activities & Outcomes

March 2010

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1. Highlights of the Pandemic Preparedness Strategic Research Initiative

By the beginning of the 21st century, the emergence of avian influenza (bird flu) heightened concerns that an influenza pandemic was close at hand. Experts estimated that up to 7 million people could die in a pandemic, including 58,000 Canadians.

In May 2006, the Government of Canada announced a $21.5 million, five-year investment in pandemic preparedness research. These funds helped the Canadian Institutes of Health Research-Institute of Infection and Immunity (CIHR-III) create the Pandemic Preparedness Strategic Research Initiative (PPSRI). CIHR-III moved quickly to develop partnerships with other agencies, who invested an additional $18.5 million and worked with CIHR-III to coordinate strategies, stimulate new research and build capacity in priority areas identified by a PPSRI Task Group.

This research preparedness was tested in 2009 with the unexpected emergence of a novel strain of H1N1 influenza virus (H1N1/09) that rapidly spread to several countries causing an influenza pandemic. While infectious symptoms were generally mild, the virus caused severe disease and death in a proportion of individuals.

Highlights of PPSRI activities include:

Funding essential pre-pandemic research
In consultation with researchers and stakeholders, PPSRI identified and began supporting research in four priority areas: vaccines and immunization, the virus, prevention and treatment, and ethical, legal and social issues. Examples of funded research include developing diagnostics, antiviral drugs and vaccines; understanding and preventing disease transmission; and identifying ethical ways to use limited resources during a pandemic.

Building research capacity
PPSRI's directed funding encourages researchers to undertake influenza and pandemic research, thereby building the national expertise. This includes a network of researchers (Public Health Agency of Canada/CIHR Influenza Research Network--PCIRN) who are developing methodologies to evaluate influenza vaccines and implement immunization programs.

Preparing for outbreak research
PPSRI helped researchers prepare for outbreak research by offering application development funds. When the H1N1 outbreak occurred, two national research teams submitted abbreviated applications for expedited peer review and funding.

Funding critical H1N1 pandemic research
CIHR worked quickly to fund research in H1N1/09 priority areas. As well, PCIRN received additional funding to have procedures in place to evaluate the pandemic vaccine.

Fostering collaborations and networks
Through the International Opportunities Program, PPSRI supports research collaborations between Canadian researchers and researchers in China, Thailand, Peru, India, Europe, and the United States. As well, support for PCIRN has created an national network of applied public health researchers..

Enhancing communication and knowledge translation
Fostering communication is a central part of PPSRI's goal. For example, PPSRI research teams must collaborate with research users, such as public health practitioners and policy makers, throughout the research project. In addition, the first annual PPSRI meeting of researchers and users of the research knowledge was held in November 2008 featuring presentations by Canadian and international authorities on pandemic and influenza research. A second meeting of influenza researchers and pandemic experts was rapidly organized and held in July 2009 to foster collaborations and research in response to the H1N1/09 pandemic.

Impact
PPSRI has already increased research capacity and strengthened linkages and partnerships for enhanced pandemic influenza planning and control. The capacity and expertise that was fostered by PPSRI enhanced our ability to respond to the H1N1/09 pandemic. In addition, knowledge from PPSRI-funded research will lead to improved methods to prevent and treat seasonal influenza and respond to future influenza pandemics. Canada must remain committed to the intense, organized and sustained effort required to be ready to rapidly respond to the next infectious disease outbreak, whenever it occurs.

2. Executive Summary

Influenza is an infectious viral disease that generally causes fever, sore throat, muscle pain, headache and fatigue. But, infections can be severe and result in several thousand deaths worldwide each year. Occasionally, a new strain of the influenza virus emerges to cause an influenza pandemic that, in the past, has resulted in several million deaths. By the early 2000s, most experts agreed that the next pandemic was overdue. An influenza pandemic could have severe health, economic and social consequences. Worldwide, between 2 million and 7.4 million people could die including 11,000 to 58,000 Canadians. It is estimated that 4.5 to 10.6 million Canadians could become ill.

Surprisingly, given the potentially devastating health, economic and social consequences of a pandemic, there are large gaps in knowledge concerning influenza. More research is needed to effectively meet the challenges of a highly virulent strain of influenza. This research will help develop new health-care strategies, policies and products that could be used to prevent or respond to a pandemic. Many countries are conducting influenza research, but it is essential to develop research capacity in Canada to meet the unique needs of this country and to have local experts available in the event of a pandemic. New research knowledge will be an essential component of an effective national annual and pandemic influenza response plan.

Recognizing the need to develop a coordinated and focused research effort and to build research capacity in pandemic influenza in Canada, the Canadian Institutes of Health Research Institute of Infection and Immunity (CIHR-III) established the Pandemic Preparedness Strategic Research Initiative (PPSRI). The mandate of the PPSRI is to identify strategic research priorities and support pandemic preparedness research. PPSRI is guided by the Pandemic Preparedness Strategic Research Initiative Task Group. The Task Group has representatives who carry out pandemic research, as well as members who apply new research knowledge. The PPSRI is supported by the Canadian federal government which announced in May 2006 that it will provide $21.5 million over five years to support pandemic influenza research.

The purpose of this report is to provide background information about the PPSRI and to summarize its activities, accomplishments and future plans. Significant progress has been made. In September 2005, CIHR-III and the Public Health Agency of Canada (PHAC) organized an Influenza Research Priorities Workshop to identify areas of seasonal and pandemic influenza research requiring support. To direct the activities of the PPSRI, the Task Group refined, developed and further prioritized the research areas first identified during the Workshop. These draft priorities were sent to stakeholders for feedback, and the comments were used to revise the priorities. The key areas identified are: i) vaccines and immunization programs, ii) the influenza virus, iii) prevention and treatment, and iv) ethics, legal and social research.

It is critical that research that addresses the strategic priorities is funded in a timely manner. To this end, CIHR-III has taken a lead role and has also collaborated with other CIHR Institutes and organizations to launch funding opportunities to build capacity in pandemic preparedness research and to support research before an outbreak. For example, in June 2006, CIHR-III launched a funding opportunity for pandemic preparedness research operating grants with emphasis on disease control, prevention measures and the health-care system. Twenty-six of the 60 applications that were received were funded. The funded research is wide-ranging and innovative. Highlights of the proposed projects include studies to discover novel antiviral drugs, to develop vaccines that would protect individuals from multiple strains of the virus, to determine the best methods to respond to a pandemic, and to identify ethical issues pertaining to a pandemic and to determine how they should be addressed.

In July 2006, CIHR-III and the CIHR International Relations Branch, as part of the International Opportunity Program, launched funding opportunities for seed and collaborative research grants to encourage and support international research collaborations in the area of pandemic preparedness research. Results of the competition were announced in March 2007. The eight researchers who received grants plan to engage in international research in areas such as determining risk factors for emerging diseases, understanding the genetic changes in influenza viruses that take place in children in different countries, determining the factors that protect individuals against influenza and the development of broad spectrum antivirals.

To continue to build research capacity and support research before a pandemic, a major round of funding opportunities was launched in December 2006. These included requests for applications for operating grants to support research that addresses influenza diagnostics, transmission, ethics review and antiviral medication, as well as team grants either in influenza biology, vaccines, ethics, legal and social research or in influenza transmission and prevention research. To support individuals with an interest in applying for these grants and to foster collaborations among them, an application development workshop was held in Ottawa in March 2007. One team grant was awarded in October 2007 to Dr. Mark Loeb who is examining influenza transmission and prevention in a model community. In March 2008, five researchers received awards under the operating grant opportunity. It is expected that the funded research will lead to rapid diagnostics, better methods for controlling disease spread and new ways to treat affected individuals.

Late in 2007, the PPSRI moved into an important second phase. The goal of this phase was to support the research community to prepare for outbreak research. To this end, CIHR-III and PHAC announced two innovative outbreak catalyst grant opportunities. One was for individual researchers or small teams to start the preparatory phase of outbreak research projects. Five researchers received grants under this funding opportunity in March 2008. The other funding opportunity was for application development funds to team leaders who can bring together a research team in a key area that will require a response when an outbreak occurs. It was anticipated that this would allow for an immediate response during an influenza pandemic because team leaders, research protocols and tools will have been identified ahead of time.

In addition to the catalyst grants, PHAC and CIHR-III collaborated to establish the PHAC/CIHR Influenza Research Network (PCIRN) with the overall objective to develop and test methodologies to evaluate the safety, immunogenicity and effectiveness of influenza vaccines and to establish methods for vaccine program implementation. An application development workshop was held in Ottawa in February 2008 to assist researchers with an interest in applying to this funding opportunity and to provide an opportunity for them to meet each other, exchange information and begin preparation of an application.

The importance of building research capacity and expertise was highlighted in April 2009 with the emergence of a novel strain of H1N1 influenza A virus (H1N1/09). The virus quickly spread from Mexico to other countries including Canada. In June 2009, the World Health Organization (WHO) announced that a pandemic was underway. While most infections were mild, a proportion of infected individuals developed severe respiratory symptoms requiring prolonged stays in intensive care units and ventilator support. Experts worried that intensive care units would be overwhelmed and that the virus would mutate to become more pathogenic.

On April 27, 2009, immediately after reports that H1N1/09 had spread to Canada, CIHR-III convened an urgent meeting of the PPSRI Task Group to develop a coordinated research response. Representatives from PHAC, the Canadian Food Inspection Agency and PCIRN were invited to join the PPSRI Task Group. The expanded Task Group worked with researchers and other experts to identify several questions that required immediate attention in the areas of transmission, infection, detection, treatment, vaccination and health services.

Approval to fund the PHAC/CIHR Influenza Research Network (PCIRN) for three years was expedited to allow a national team of over 80 scientists from 30 research institutions across Canada to immediately start work on evaluating a pandemic vaccine when it was released. Working with the PHAC and provincial and municipal public health authorities, the network will inform Canadian immunization procedures and policies both during the 2009 pandemic and in preparing for annual seasonal influenza outbreaks.

Recipients of the Pandemic Outbreak Team Leader Catalyst Grants were asked to submit H1N1 research proposals, which received unprecedented acceleration through the funding system. The program is supporting the work of two national research teams: one based at Université Laval that will study the genetic evolution of pandemic H1N1/09 influenza virus and its susceptibility to antiviral drugs; and one at the University of British Columbia that will use mathematical models to understand the transmission and spread of the virus.

In early July 2009, CIHR-III announced $1.2 million for the Catalyst Grant: Pandemic Outbreak Research Response funding opportunity. Its aim was to bring together researchers in outbreak priority research areas by supporting team planning and development activities. With short deadlines for application submission, peer review and funding approval, research teams were funded in October 2009. In addition to these activities, CIHR and partners have held two annual meetings of pandemic and influenza researchers and end-users of the knowledge created. The first meeting took place in Winnipeg in November 2008 and brought together 150 participants. The second meeting, organized rapidly in response to the H1N1 pandemic, was held in Toronto in July 2009 and had over 180 participants. The meetings have provided an overview of the current state of pandemic and influenza research, built collaboration amongst researchers and linkages to knowledge-users, and supported knowledge translation of research findings.

The research and activities supported by PPSRI enhanced Canada's research response to the H1N1/09 influenza virus. It is anticipated that research and activities that are ongoing will help to identify strategies to prevent or mitigate a future pandemic outbreak, including new methods and procedures to control disease spread (both human-to-human and from animals to humans) and to treat affected individuals. In addition, the international research collaborations established and supported through the International Opportunities Program, Team Grants and the PPSRI Annual Meeting will enhance linkages amongst Canadian and international researchers. This is important because the threat of an influenza pandemic is global.

3. Introduction

CIHR-III is leading the PPSRI to develop a coordinated and focused research effort and to build influenza and pandemic preparedness research capacity in Canada. Work includes identifying current gaps in knowledge and supporting research training, operating grants, teams and multidisciplinary approaches to pandemic preparedness. The PPSRI also supports knowledge translation activities to ensure that research results are rapidly taken up by end users. The ultimate goal is that the new knowledge will allow Canada and others around the world to prevent or mitigate an influenza pandemic. The purpose of this report is to provide background information about the Initiative and to summarize the activities, accomplishments and future plans of the PPSRI.

4. Background

At the start of the 21st century, most experts agreed that an influenza pandemic was overdue. A cause of concern is the human deaths caused by a new highly pathogenic strain of influenza A virus (H5N1) that emerged in south-east Asia in the late 1990s, which has spread widely in birds, the natural reservoir for the virus. By June 2008, the World Health Organization had confirmed 385 cases of human H5N1 infection and 243 deaths. It was not known whether H5N1, or some other strain, would cause the next pandemic.

PHAC has estimated that, in the event of a severe influenza pandemic, 4.5 to 10.6 million Canadians will become clinically ill, 2 to 5 million will require outpatient care, 34,000 to 138,000 will require hospitalization and that 11,000 to 58,000 will die. The World Health Organization has suggested that worldwide between 2 million and 7.4 million people could die from a global influenza pandemic.

The World Health Organization and public health agencies in many countries have developed plans to prevent and prepare for a pandemic. Canada was one of the first countries to develop a preparedness and response strategy, the Canadian Pandemic Influenza Plan for the Health Sector. The Plan was developed to assist with the main components of planning, including surveillance, vaccine programs, use of antivirals, health services, emergency services, public health measures and communications.

Surprisingly, considering the scope of the potential health, economic and social consequences of pandemic influenza, there are severe gaps in knowledge about the virus. For example, questions remain about the prevention of influenza transmission and treatment of the disease. There has also been a lack of discussion and consensus concerning ethical and social issues, such as the allocation of scarce resources during a pandemic. Acquiring knowledge in these and other areas will facilitate development of new health-care system strategies, policies and products for pandemic preparedness. Therefore, in addition to public health planning, it is critical to mount a comprehensive influenza research initiative. Ultimately, the knowledge acquired will be an essential component of an effective national annual influenza and pandemic influenza response plan.

Other countries have, and continue to develop, research responses to pandemic influenza. In the USA, for example, influenza pandemic preparedness research is a priority of the American government. Examples of current research projects include H5N1 vaccine clinical trials being run by the National Institutes of Health (NIH) vaccine treatment and evaluation units, as well as the National Institute of Allergy and Infectious Diseases' (NIAID) influenza genome project. Additionally, the NIH and NIAID Cooperative Research Partnership for Influenza Product Development supports research leading to the discovery and development of therapeutics, diagnostics and vaccines for influenza.

The Medical Research Council in the United Kingdom is also supporting research in several identified priority areas. These include the modes of transmission of avian flu to humans, the molecular and cellular mechanisms of virulence and pathogenicity, mechanisms of immune protection, creation of improved vaccines, effective use of antivirals, development of rapid diagnostics and determination of methods to prevent the spread of infection.

In Canada, CIHR-III has led the way in developing and supporting pandemic influenza preparedness research. CIHR-III established the PPSRI to support research with the goal to improve Canada's ability to prevent and/or respond to an influenza pandemic. Another objective is to facilitate collaboration and linkages amongst researchers and end-users of the new research knowledge in order to ensure that research results are translated in a timely fashion. It is essential to build a network of researchers and end-users in Canada, to address issues unique to this country and so that local experts and knowledge are available during a pandemic.

The Initiative is funded by the Canadian federal government which announced in May 2006 that it would provide $21.5 million over five years to CIHR to support pandemic preparedness activities.

The importance of supporting pandemic preparedness research and building research capacity and expertise in influenza was reinforced with the emergence of a novel pandemic strain of H1N1 influenza A virus (H1N1/09) in April 2009. The virus quickly spread from Mexico to other countries including Canada. In June 2009, the World Health Organization (WHO) issued a phase 6 pandemic influenza alert indicating that an influenza pandemic was underway. While most infected individuals experienced mild symptoms, a proportion developed severe respiratory symptoms requiring prolonged stays in intensive care units and ventilator support. Experts worried that intensive care units would be overwhelmed, and that the virus would mutate to become more pathogenic.

5. Report on Activities

5.1 Influenza Research Priorities Workshop

CIHR-III and PHAC organized the Influenza Research Priorities Workshop in Ottawa in September 2005. Ten research areas were identified by national and international influenza experts attending the Workshop. Pandemic influenza was recommended as a major research focus in the short term. Participants discussed gaps in knowledge, research activities to help bridge the gaps and infrastructure and capacity requirements that are currently lacking. See the Institute website for the Workshop report.

5.2 Pandemic Preparedness Strategic Research Initiative Task Group

To develop and guide the PPSRI, CIHR-III formed the PPSRI Task Group. The Task Group includes members carrying out pandemic research, as well as members who will apply the new research knowledge to help Canada prepare for and respond to a pandemic (see Appendix 1 for a list of members and their expertise). The mandate of the Task Group encompasses the following objectives: to make recommendations on strategic research priorities and mechanisms to support these areas; to develop outcome indicators/measures for research; to facilitate research linkages; to identify national and international experts to act as peer reviewers; and to identify partners and obtain funding to support necessary research activities.

5.3 Draft Pandemic Preparedness Strategic Research Priorities

To support the PPSRI and direct its future activities, the Task Group refined, developed and further prioritized the research areas first identified during the Influenza Research Priorities Workshop. The objective of the Task Group was to identify areas in which Canadian researchers could obtain results that would have a significant impact on the ability to prevent and/or respond to an influenza pandemic. The Task Group considered current pandemic and annual influenza research in progress in Canada and internationally, and identified gaps in research that Canadian researchers are well positioned to fill. The implications of potential research results in specific areas were also considered.

The Task Group felt that vaccine research should form the cornerstone of an influenza pandemic preparedness research effort, because an effective vaccine is key to stopping a pandemic. To develop vaccines and assist in the prevention of infection and treatment of influenza, fundamental knowledge about the influenza virus and molecular mechanisms of transmission is needed. And, in the event that a vaccine for a new strain of influenza is not available at the start of a pandemic, methods to prevent the spread of the virus and to treat affected individuals will also be critical. The Task Group determined that preparing for and responding to a pandemic raises many ethical, legal, social and societal issues, many of which relate to the other broad research areas. They also noted that research carried out under the PPSRI will impact and inform future responses to annual influenza outbreaks. Detailed descriptions of each priority are contained in the next section of the report.

The research priorities identified by the Task Group reflect areas that require investment through strategic initiatives such as targeted funding opportunities. The priorities are not intended to lessen the importance of other areas of influenza and infectious disease research, which remain eligible for funding through regular grant programs and other targeted initiatives offered by CIHR and other funding agencies.

5.4 Consultation Process with Stakeholders

The draft pandemic preparedness strategic research priorities were sent to the Canadian Rapid Research Response Team and additional stakeholders in pandemic-related fields. For a list of those who were consulted, see Appendix 2. The purpose of the consultation was to give stakeholders an opportunity to review the draft priorities and provide feedback. The consultation also helped to create linkages with organizations working in areas related to pandemic preparedness, as well as users of research knowledge nationally and internationally.

The PPSRI received 16 responses to the consultation request. The overwhelming majority agreed that each of the draft areas identified by the Task Group was a priority for Canadian research. The comments were incorporated, and the finalized priorities are presented below in a summary of the strategic research priority areas. The following organizations indicated they would like to partner in supporting one or more of the research areas:

American Red Cross
Canadian Food Inspection Agency
Association of Medical Microbiology and Infectious Disease Canada / Canadian Foundation for Infectious Diseases
Canadian International Development Agency
Emerging Infectious Disease Research Network
First Nations and Inuit Health Branch, Health Canada
Rx&D (an association of Canada's research-based pharmaceutical companies) Health Research Foundation
International Development Research Centre
Public Health Agency of Canada

5.5 Pandemic Preparedness Strategic Research Priorities

5.5.1 Pandemic Preparedness Strategic Research Priorities (2006)

The following is a summary of the Pandemic Preparedness Strategic Research Priorities that were developed in 2006 by the Task Group in consultation with stakeholders. These priorities direct the activities of the PPSRI.

Capacity Building

An overarching theme is the need to build capacity in pandemic influenza research in Canada. It is essential for Canada to build research expertise now so that it will have expert researchers to call on during a pandemic outbreak. The Task Group felt that the best way to achieve this is to support training in influenza research, such as doctoral and fellowship support, as a component of operating and team grants.

Vaccines and immunization programs: optimal use and efficiency of existing vaccines and development of new pandemic vaccines

Research is needed to further our understanding of immune response and protection, as well as to devise new vaccine technologies. Effective vaccination strategies would greatly reduce the impact of a new strain of influenza.

Research is required to: optimize existing vaccination programs; aid in the discovery of novel means of vaccine delivery; examine scheduling and dosing; and address issues of safety.

Proposed projects to further our understanding of immune response and protection would: study human and animal immune responses to immunization and indicators of protective immunity; assess the carry-over and cross-protection by vaccines; develop cross-protective vaccines; study the effectiveness of human vaccines to prevent reassortment of animal and human influenza; and develop novel influenza virus vaccine technologies and new vaccine platforms.

Research is also needed to: develop better assessments of the potential benefits and short- and long-term safety of influenza vaccines in specific populations, study and measure the economic benefits of immunization, develop methodologies and capacity for annual assessment of program effectiveness.

The virus: biology of the influenza virus and rapid diagnostics

Much more information is needed about the influenza virus and reliable and rapid diagnostic tests for influenza are currently not available.

Research is needed on: the biology of the influenza virus; the human and animal host response to infection such as the innate and acquired immune response; and the role of mucosal immunity and correlates (predictors) of protection. Recommended research would also include: studies to investigate the genetics of influenza; analysis of influenza evolution in avian and mammalian species; and assessment of disease production and immune response using animal and human models.

Research is required to develop and evaluate rapid diagnostic tests for hospital laboratories and "point-of-care" applications which, at the present time, are not available. Research would also evaluate the utility and impact of optimized diagnostic testing.

Prevention and treatment: modes of transmission, use of antivirals and alternate strategies for prevention

In the event of a pandemic, knowledge of ways to prevent the spread of the virus and to treat infected individuals will be critical. Further knowledge is needed on how influenza spreads in different settings.

Research is required to study: the molecular basis for transmission of the influenza virus between humans, as well as from animals; the mechanisms involved in pathogenesis; the mode of transmission including influenza shedding patterns; and, the risk factors for infection. Research is also required to determine optimal methods of preventing transmission at the individual, institutional and community level. Research areas include comparison of protective equipment such as masks, the utility of vaccination of specific populations and the value of increasing social distancing and containment.

There is a need for new antivirals in light of the limited number that are currently available, but discovery of new drug targets and development of new antivirals are long-term projects. In a pandemic, it will be critical to optimally use existing limited supplies of antiviral drugs such as Tamiflu. Research is needed to determine the optimal dosing, effects on various influenza strains, usage in a variety of settings and degree of development of viral resistance to antivirals. Research might also include discovery of innovative uses of existing antivirals, as well as discovery of existing drugs that have an antiviral effect.

Ethics, legal and social contract: research in risk communication, prioritization and the regulatory approval process

It is essential that research and discussions that aid in the planning of how to prevent and respond to a pandemic are in place before a pandemic starts. Research is needed to develop and optimize communication strategies, determine effective means to educate health care providers in the application of care guidelines and to identify effective protective measures in the Canadian context. There is a need for research to address the issues of surge capacity in pandemic situations. Research into prioritization and resource allocation could address global, hospital, and bedside requirements, fairness of distribution of limited resources and would take into account ethical issues. Ethics research is needed to examine the perceptions among health care providers and the public on the scope and extent of obligations and duty to care during a pandemic. Research is needed to understand the social, economic, cultural and secondary impact of such measures and examine the needs of vulnerable populations and children in pandemic outbreaks.

In the event of a pandemic, new therapeutics and diagnostics will require expeditious approval in a manner that protects human subjects. Research is needed into ways to improve efficiency of the ethics review process. This would include development of models, processes, guidelines and standard operating procedures to allow the research community and research ethics review boards to submit and process applications related to public health threats quickly.

There are opportunities to learn from the research work carried out in this area during the Severe Acute Respiratory Syndrome (SARS) outbreak. As a starting point, research could take the form of analysis of funded SARS research and lessons learned from that research.

5.5.2 H1N1/09 Pandemic Strategic Research Priorities

At the end of April 2009, immediately after reports that the pandemic H1N1 influenza virus had spread to Canada, CIHR-III convened an urgent meeting of the PPSRI Task Group to coordinate research efforts. The Task Group was expanded to include key representatives from the PHAC, the Canadian Food Inspection Agency and the newly formed PHAC/CIHR Influenza Research Network on Vaccine Evaluation (see Appendix 1).

In May 2009, CIHR-III and the expanded Task Group invited researchers to participate in a series of teleconferences to discuss research priorities and ways to facilitate research. The Task Group reviewed recommendations and developed the following strategic areas:

Transmission

What is the mode of transmission of H1N1/09 including viral shedding patterns?
What are the medical, economic and other costs of possible transmission of H1N1/09 compared to those associated with practices to avoid transmission (e.g., development of a vaccine)?
How can the ethical issues related to the use of social distancing measures, such as school closures, be resolved?

Infection

Why do severe infections from H1N1/09 appear to be more common in pregnant women and in First Nations, Metis and/or Inuit people?
What immune responses reduce/increase the severity of infection?
What is the role co-infection, genetics and the environment in transmission and disease course?
What is the pathogenesis of viral infection including the long-term effects of severe disease?
What is the role of pre-existing influenza immunity in offering cross-protection?

Detection

How is the virus evolving in humans and pigs, especially with respect to antiviral resistance and enhanced virulence?
What new rapid point-of-care diagnostic tests will detect the virus, and is there a way to exploit new technologies?

Treatment

What is the efficacy and safety of antiviral drugs and how can resistance be minimized?
What is the public consensus regarding the acceptability of priority setting schemes for antivirals and hospital resources?
What are the best health system strategies for treating of those affected, while minimizing untoward effects on others?

Vaccination

What types of immune responses offer protection?
Is there evidence for antigen competition when flu vaccines are used together?
Do specific vaccine types reduce flu-associated morbidity/mortality?
Do existing vaccines offer cross-protection against H1N1?
How can ethical issues in rapid vaccine deployment such as priority setting and compensation for vaccine-related harm be resolved?

The Task Group continued to meet regularly by teleconference to review research strategies and respond to changing issues throughout 2009 and into 2010.

5.6 Funding Opportunities and Research Supported

It is critical that the strategic research priorities identified during the Influenza Research Priorities Workshop and by the PPSRI Task Group are funded in a timely manner. To this end, CIHR-III has taken a lead role and has also collaborated with other CIHR Institutes and organizations to launch several funding opportunities to support pandemic preparedness research. The applications have been peer-reviewed, grants have been awarded to successful applicants and research is underway. These funding opportunities and the research supported are summarized in section 5.6.1. The PPSRI has also supported pandemic preparedness research by providing funds to successful applicants to other programs or initiatives, providing the research proposed addresses one or more of the PPSRI strategic priorities. These funding opportunities and the research supported are described in section 5.6.2.

5.6.1 Funding Opportunities Led by the PPSRI and Summary of the Research Supported

Operating Grants: Pandemic Preparedness
Funding Opportunity
Funding Decision

In June 2006, CIHR-III, PHAC and Mathematics of Information Technology and Complex Systems (MITACS; a Network of Centres of Excellence) launched this first funding opportunity to address the recommendations made at the Influenza Research Priorities Workshop. The purpose is to further strengthen Canadian influenza research in preparation for a potential pandemic outbreak by funding two-year projects to conduct critical research on disease control, prevention measures and health-care system preparedness. In August 2006, CIHR-III received a strong response to this opportunity with the receipt of 60 applications, and 26 were funded in February 2007 (Table 5.6.1.1). The research proposed is wide-ranging and innovative, and will be vital to help Canada and the rest of the world prepare for a potential pandemic outbreak. For example, it is anticipated that the research will lead to novel methods to detect pandemic strains of influenza, to a universal influenza vaccine that would protect against multiple strains of influenza, to new ways to prevent the spread of the virus and to treat people with influenza infections, to improved health-care strategies and to a better understanding of ethical issues pertaining to a pandemic and how they should be addressed. The funding also supports and helps to build influenza research capacity in Canada, which is essential to meet the unique needs of this country and to ensure that local experts are available in the event of a pandemic. See Appendix 3.1 for project summaries.

Table 5.6.1.1 – Projects Funded under the Operating Grants: Pandemic Preparedness Funding Opportunity
Principal Investigator	Host Institution	Project Title
Boivin, Guy	Université Laval	Mechanisms of resistance of influenza to antiviral agents and evaluation of new therapeutic modalities
Buckeridge, David	McGill University	Understanding epidemics in special populations: Guiding intervention and planning
Coombs, Kevin	University of Manitoba	Proteomics of influenza virus-infected human cells
Dascal, André	Sir Mortimer B. Davis Jewish General Hospital (Montreal)	Ability and willingness of health care workers to report for work in an influenza pandemic
Day, Robert	Université de Sherbrooke	Antiviral inhibitors of furin and related convertases
Earn, David	McMaster University	Consequences of evolution for pandemic preparedness
Gutfreund, Klaus	University of Alberta	Immunotargeting with CD154 to induce antiviral immunity to avian influenza
Kelvin, David	University Health Network (Toronto)	The role of complement cascades in pathogenesis of H5N1 disease
Kenny, Nuala	Dalhousie University	Pandemic planning and foundational ethical questions of justice, the common good and the public interest
King, Malcolm	University of Alberta	Cough and bioaerosol in influenza pandemic containment
Kobinger, Gary	University of Manitoba	In vivo evaluation of conventional and experimental avian influenza A (H5N1) virus vaccines
Lapointe, Réjean	Centre hospitalier de l'Université de Montréal	Development of a pan-specific cellular immune response to influenza
Leclerc, Denis	Université Laval	Development of a universal influenza vaccine candidate
Magor, Katherine	University of Alberta	Antiviral responses to influenza in the natural host
Maunder, Robert	Mount Sinai Hospital	Education and support to increase the resilience of health-care workers facing pandemic influenza: What is the minimum effective dose?
Nicholas, David	Hospital for Sick Children (Toronto)	Pandemic planning for paediatric care
Pante, Nelly	University of British Columbia	Toward the development of novel anti-influenza drugs that block nuclear import of influenza
Predy, Gerald	Capital Health Region (Edmonton)	Feasibility and effectiveness of a community triage centre to manage influenza-like illness in an urban setting
Skowronski, Danuta	University of British Columbia	Influenza vaccine effectiveness against serious outcomes
Skowronski, Danuta	University of British Columbia	From genotype to phenotype: Early detection of influenza variants and correlation with variation in vaccine effectiveness
Suresh, Mavanur	University of Alberta	Targeted dendritic cell vaccines for influenza: Providing a vaccine to all 33M Canadians
Tellier, Raymond	Hospital for Sick Children (Toronto)	Early detection of avian influenza isolates with increased affinity for the human sialic acid receptor
Upshur, Ross	University of Toronto	Ethics and pandemic planning: Engaging the voices of the public
von Messling, Veronika	Institut national de la recherche scientifique (Québec)	Pandemic potential assessment of recent animal influenza isolates
Watts, Tania	University of Toronto	Mouse models for evaluating the protective value of increased costimulation of CD8 T cell responses in the lung
Zhou, Yan	University of Saskatchewan	The role of PI3K/Akt pathway in modulating chemokine IP-10/CXCL10 production by influenza A virus infection in human airway epithelial cells

CIHR International Opportunity Program: Seed and Other Grants
Funding Opportunity: Opportunity 1 and Opportunity 2
Funding Decision

CIHR-III and the CIHR International Relations Branch issued a joint call for applications to the International Opportunity Program for both seed and collaborative research project grants that are relevant to pandemic preparedness in July 2006. The purpose of the seed grants is to assist Canadian researchers to explore, develop and establish new international collaborations with foreign researchers. These one-time grants support Canadian participation in the pre-research stages that will lead to new international research collaborations. The Other Collaborative Research Grant enables Canadian researchers to participate in international research projects approved for funding by foreign entities in which the Canadian participants must secure their own funding.

The importance that CIHR-III places on establishing international collaborations is evidenced by its participation in a re-launch of the funding opportunity for International Opportunity Program Seed Grants in October 2006.

Eight grants were awarded under the program in March 2007 (Table 5.6.1.2). It is anticipated that the results of the research will improve our ability to prevent and treat pandemic influenza and will foster necessary international research linkages in this important area. See Appendix 3.2 for project summaries.

Table 5.6.1.2 – Projects Funded under the CIHR International Opportunity Program
Seed Grants
Principal Investigator	Host Institution	Project Title
Brewer, Timothy	McGill University Health Centre	Risk factors for emerging diseases
Brown, Earl	University of Ottawa	Evolution of interferon resistance of avian and human influenza viruses
Fish, Eleanor	University Health Network (Toronto)	Canada-EU collaboration: Development of broad-spectrum antivirals
McElhaney, Janet	Vancouver Coastal Health Research Institute	The roadmap to improved correlates of protection against influenza
O'Callaghan, Christopher	Queen's University (Kingston, Ontario)	Building global capacity for evidence-based research in communicable diseases
Pourbohloul, Babak	University of British Columbia	Pandemic preparedness: An international modeling exchange
Tran, Dat	Hospital for Sick Children (Toronto)	Genetic epidemiology of influenza: A multinational pediatric initiative
Other Collaborative Research Grants
Principal Investigator	Host Institution	Project Title
von Messling, Veronika	Institut national de la recherche scientifique (Québec)	Characterizing the potential and mechanism of type I interferons as influenza treatment

Team Grants: Influenza Transmission and Prevention
Funding Opportunity
Funding Decision

In December 2006, CIHR-III and CIHR/Rx&D Collaborative Research Program launched this funding opportunity in partnership with Canada's Research-Based Pharmaceutical Companies (Rx&D) Health Research Foundation 2006, the Canadian Food Inspection Agency, CIHR Institute of Aboriginal Peoples' Health and the International Development Research Centre. The objective of the CIHR Team Grant program is to strengthen Canadian health research by supporting teams of talented and experienced researchers conducting high-quality research and providing superior research training and mentorship. It is anticipated that the results will be realized more rapidly and more efficiently through the CIHR Team Grant program than if the components were to be funded as a series of separate operating grants.

The goal of this funding opportunity was to fund three-year team grants to study the modes of transmission of the influenza virus and alternative strategies for prevention of infections. Dr. Mark Loeb from McMaster University and his team were awarded a grant in October 2007 to examine influenza transmission and prevention in a model community (Table 5.6.1.3). The results of this research will form the basis of policy decisions on how best to prevent the spread of annual and pandemic influenza. See Appendix 3.3 for a project summary.

Table 5.6.1.3 – Project Funded under the Team Grants: Influenza Transmission and Prevention Funding Opportunity
Principal Investigator	Host Institution	Project Title
Loeb, Mark	McMaster University	HRF/CIHR/CFIA Team in Influenza –Transmission and prevention of influenza among Hutterites: A model for pandemic preparedness

Operating Grants: Influenza Diagnostics, Transmission, Ethics Review and Antivirals
Funding Opportunity
Funding Decision

CIHR-III launched this funding opportunity in collaboration with the PHAC, CIHR Institute of Aboriginal Peoples' Health, Canadian Foundation for Infectious Diseases and Association of Medical Microbiology and Infectious Disease Canada in December 2006. The purpose is to fund three-year research projects that will examine the optimal use of existing antivirals, disease transmission, rapid diagnostics and the ethics review process. Funding decisions were made in March 2008. Of the nine applications that were received, five were funded (Table 5.6.1.4). It is expected that the funded research will lead to rapid diagnostics, better methods for controlling disease spread and new ways to treat affected individuals. See Appendix 3.4 for project summaries.

Table 5.6.1.4 – Projects Funded under the Operating Grants: Influenza Diagnostics, Transmission, Ethics Review and Antivirals Funding Opportunity
Principal Investigator	Host Institution	Project Title
Boivin, Guy	Université Laval	Mechanisms of influenza resistance to neuraminidase inhibitors and evaluation of new therapeutic modalities
Borgeat, Pierre	Université Laval	A rationale approach towards alternative pharmacological interventions in the treatment of influenza virus infection.
Krahn, Murray	University Health Network (Toronto)	The cost-effectiveness of pandemic influenza Mitigation strategies using a stochastic, agent-based transmission model
Richter, Martin	Université de Sherbrooke	Targeting host cell mechanisms: A novel approach to anti-influenza prophylaxis and therapy, and the study of the subsequent host immune response
Smieja, Marek	McMaster University	Rapid molecular diagnostics for influenza

Team Grants: Influenza Biology, Vaccines, Ethics, Legal and Social Research
Funding Opportunity
Funding Decision

Also in December 2006, CIHR-III launched this funding opportunity in collaboration with the PHAC, CIHR Institute of Aboriginal Peoples' Health, Ethics Office of CIHR and the Canadian Food Inspection Agency. The purpose is to fund three-year team grants on vaccines, the biology of the influenza virus, including the animal-human interface, and the social, ethical and legal issues related to preventing and responding to a pandemic. Expected outcomes of funded research (Table 5.6.1.5) are the identification of strategies to prevent or mitigate a pandemic outbreak, as well as methods and procedures to control disease spread between humans and from animals to humans, and to treat affected individuals. See Appendix 3.5 for project summaries

Table 5.6.1.5 – Projects Funded under the Team Grants: Influenza Biology, Vaccines, Ethics, Legal and Social Research Funding Opportunity
Principal Investigator	Host Institution	Project Title
Agrawal, Babita	University of Alberta	Investigation of Novel Vaccine Strategies for Influenza: Targeting Innate and Adaptive Immunity for Cross-protective Vaccines
Boivin, Guy	Université Laval	Optimization of influenza vaccines for human and avian influenza strains
Brown, Earl	University of Ottawa	Natural and Experimental Models of Evolution of Influenza A Viruses.
Feldmann, Heinz	University of Manitoba	Comparison and basis of efficacy in commercial conventional vaccines against the H5N1 influenza virus.
Jean, François	University of British Columbia	CIHR Team Grant in the Functional Infectomics of H5/H7 Influenza A Virus.
McCarthy, Anne	Ottawa Health Research Institute	Optimizing Health Care Worker Interpandemic Vaccine Uptake in Acute and Long Term
Skowronski, Danuta	University of British Columbia	Sentinel Network to Monitor Influenza Vaccine Effectiveness During Annual Outbreaks and Pandemics
Upshur, Ross	University of Toronto	Canadian Program of Research on Ethics in a Pandemic (CanPREP): Whose risks, whose duties, and what priorities?
Watts, Tania	University of Toronto	Correlates of Protection Against Influenza Illness: From Mouse Models to Older Adults

Research Syntheses: Knowledge Translation
Funding Opportunity

CIHR-III launched this funding opportunity in December 2006 in partnership with the CIHR Knowledge Translation Branch. The purpose is to strengthen knowledge translation by funding research syntheses related to preparing for and responding to an influenza pandemic. There are opportunities to learn from research work carried out during the Severe Acute Respiratory Syndrome (SARS) and other disease outbreaks. No applications related to pandemic preparedness were received.

Workshop/Symposia Support in collaboration with Knowledge Translation Branch
Funding Opportunity
Funding Decision

CIHR-III and the CIHR Knowledge Translation Branch announced in December 2006 that they will provide partial support of workshops and symposia that either support knowledge translation research and/or contribute to building networks relevant to pandemic research in order to assist in pandemic preparedness planning and pandemic control. Dr. Thomas Coleman and his colleagues were awarded a grant in February 2008 to support a symposium he is organizing in Toronto entitled: Pandemic Preparedness: Strategies and Tools (Table 5.6.1.6). Experts in quantitative methods for pandemic planning and in public health will discuss methods to enhance pandemic preparedness and to develop the most appropriate response plan. See Appendix 3.6 for a project summary.

Table 5.6.1.6 – Projects Funded under the Workshop/Symposia Support in collaboration with Knowledge Translation Branch Funding Opportunity
Principal Investigator	Host Institution	Project Title
Coleman, Thomas	University of Waterloo	Pandemic Preparedness: Strategies and Tools

Application Development Workshop

An application development workshop for researchers with an interest in submitting applications to the December 2006 funding opportunities was held in Ottawa in March 2007. Over 20 individuals, including researchers with expertise in influenza and vaccine evaluation, participated in the workshop. The purpose of the workshop was to assist researchers in the application process by providing a review of the relevant research areas in the funding opportunity, a description of the goals of the organizations collaborating to fund this research and information about writing a successful grant application. The workshop also allowed researchers to meet each other to discuss areas of common interest. Participants stated that the meeting was effective in enhancing linkages and helping them begin to plan an application.

Catalyst Grant: Mobilization of the Research Community for Outbreak Response
Funding Opportunity
Funding Decision

At the PPSRI Application Development Workshop held in March 2007, participants highlighted a need for research planning and preparation before an outbreak occurs to enable the research community to be poised to act immediately in the event of a pandemic. This funding opportunity, launched by CIHR-III and PHAC in September 2007, will support researchers by funding catalyst grants for individual researchers or small teams to start the planning and preparatory phase of research projects that will be essential for pandemic control during an outbreak, and to gather data for analysis in order to develop recommendations to prevent or mitigate future outbreaks. A total of 14 applications were received, and five were funded in March 2008 (Table 5.6.1.7). See Appendix 3.7 for project summaries.

Table 5.6.1.7 – Projects Funded under the Catalyst Grant: Mobilization of the Research Community for Outbreak Response Funding Opportunity
Principal Investigator	Host Institution	Project Title
Bisaillon, Martin	Université de Sherbrooke	Development of a SOFA-ribozyme-based strategy to control the propagation of the influenza virus
Buckeridge, David	McGill University	Evaluating the population effect of a new vaccination policy: An international comparison
Christian, Michael	Mount Sinai Hospital (Toronto)	Prognostic scoring for patients with severe disease due to influenza
McGeer, Allison	Mount Sinai Hospital (Toronto)	Pandemic research priorities in influenza transmission and its prevention
Tran, Dat	Hospital for Sick Children (Toronto)	Genetic determinants of influenza severity in children: A pre-pandemic community-based feasibility study

Operating Grant: Winter2008 Priority Announcement (Pandemic Preparedness)
Funding Opportunity

In December 2007, CIHR-III and PHAC launched this priority announcement to fund three-year operating grants to address questions of influenza transmission, the effectiveness of public health control measures and the fostering of compliance with public health control measures. It is anticipated that this research will lead to the identification of effective public health control measures for responding to an influenza pandemic and controlling disease spread, and the identification of effective strategies for improving compliance with such measures. No grants were funded through this opportunity.

Catalyst Grant: Pandemic Outbreak Team Leader
Funding Opportunity
Funding Decision

CIHR-III and PHAC launched this program in December 2007 with the goal to provide application development funds to team leaders with expertise in the areas of influenza and pandemic who can bring together a research team in key areas that will require a research response when an outbreak occurs. Developing research teams before a pandemic ensured that teams of qualified researchers were in place to rapidly respond to an outbreak. A total of three applications were received and two were funded in January 2009 (Table 5.6.1.8). Dr. Guy Boivin and his research team planned to develop a national network to assess the evolution of influenza stains during a major influenza outbreak with a focus on the development of antiviral resistance. Dr. Babak Pourbohloul created a research team to develop mathematical models in order to improve Canada's response to any potential threat from emerging infections, both nationally and internationally.

With the advent of the H1N1 pandemic in April 2009, both team leaders were asked to provide further details of their research plans. The plans received unprecedented acceleration through the funding system, and funding was approved on June 16, 2009. See Appendix 3.8 for further details on the pre-pandemic and H1N1 2009 phases of the research projects.

Table 5.6.1.8 – Projects Funded under the Catalyst Grant: Pandemic Outbreak Team Leader
Principal Investigator	Host Institution	Project Title
Boivin, Guy	Université Laval	National network for characterization of influenza virus evolution and antiviral drug susceptibility
Pourbohloul, Babak	University of British Columbia	Catalyst Grant: Pandemic Outbreak Team Leader in Mathematical Modeling

Influenza Research Network
Funding Opportunity
Funding Decision (Letter of Intent): http://www.cihr-irsc.gc.ca/e/decision_media/2008/200805irl_e.pdf

CIHR-III, and PHAC, announced a funding opportunity in December 2007 to establish an Influenza Research Network. Its overall objective is to develop and test methodologies to evaluate the safety, immunogenicity and effectiveness of influenza vaccines and to establish methods for vaccine program implementation. The network will consist of a network leader who must be a researcher with proven leadership capabilities and experience and at least five additional independent investigators who have an established research track record in areas related to the collaborative project. Dr. Scott Halperin from Dalhousie University and a team of researchers from across Canada were invited to submit a full application in October 2008 following acceptance of their Letter of Intent in May 2008.

Approval for $10.8 million over 3 years to fund the PHAC/CIHR Influenza Research Network (PCIRN) led by Dr. Halperin was expedited to allow a national team of over 80 scientists from 30 research institutions across Canada to immediately start work on evaluating the pandemic H1N1/09 vaccine. To speed this process, PCIRN received an additional $2.7 million in August 2009. Working with the PHAC and provincial and municipal public health authorities, the network informed Canadian immunization procedures and policies both during the H1N1 pandemic and in preparing for annual seasonal influenza outbreaks. See Appendix 3.9 for details.

Influenza Research Network Application Development Workshop

An application development workshop for researchers with an interest in submitting an application to the Influenza Research Network funding opportunity was held in Ottawa in February 2008. The purpose of the workshop was to assist researchers in gaining an understanding of the application process and the expectations of the sponsoring organizations. The workshop also provided an opportunity for researchers to meet each other, exchange information and begin preparation of an application.

Catalyst Grant: Pandemic Preparedness (2008)
Funding Opportunity
Funding Decision

The purpose of this funding opportunity was to provide funds to researchers to start the planning and preparatory phase of research projects that will be essential for pandemic control during an outbreak or to collect information to develop recommendations to prevent or mitigate future outbreaks. A total of seven applications were received, and three were funded in March 2009 (Table 5.6.1.9). Dr. Skowronski at the University of British Columbia, for example, is developing a surveillance network to better understand the risk of serious outcomes due to influenza in pregnant women. Through the network, she will also assess influenza vaccine uptake and its role in protection against flu in pregnancy. See Appendix 3.10 for summaries of all funded research projects.

Table 5.6.1.9 – Projects Funded under the Catalyst Grant: Pandemic Preparedness (2008)
Principal Investigator	Host Institution	Project Title
Moghadas, Seyed	University of Winnipeg	PAP Evaluation of Mitigation Strategies for Pandemic Preparedness in Canada
Pourbohloul, Babak	University of British Columbia	Pan-Canadian Decision-Making Support Network for Pandemic Preparedness
Skowronski, Danuta	University of British Columbia	Burden of Influenza And Its Prevention In Pregnancy

Meetings, Planning and Dissemination Grant: Infection and Immunity (2008)
Funding Opportunity
Funding Decision

Dr. Anne McCarthy from the Ottawa Health Research Institute received a Meetings, Planning and Dissemination Grant to bring together stakeholders, immunization champions and end-users of vaccines in Winnipeg in June 2009. The purpose of the meeting is to assist in establishing the Canadian Influenza Knowledge Exchange Network. The Network will help to increase vaccination rates among healthcare workers by providing information to healthcare administrators and occupational health immunization planners. See Appendix 3.11 for further details.

Meetings, Planning and Dissemination Grant: End of Grant Knowledge Translation Supplement (2008)
Funding Opportunity

The Knowledge Synthesis and Exchange (KSE) Branch in partnership with CIHR-III will provide supplemental funding for knowledge translation activities following the completion of a CIHR grant, or component of a grant, when it is appropriate to disseminate the results of the research beyond the traditional scientific community and using methods supplementary to and in addition to publication in peer reviewed journals.

Operating Grant: Fall 2008 Priority Announcement (Pandemic Preparedness)
Funding Opportunity

This Priority Announcement on the Fall 2008 CIHR Operating Grant competitions offers additional sources of funding for highly rated applications that are relevant to pandemic preparedness and the current pandemic influenza threat.

Knowledge Synthesis Grant (2008-2009)
Funding Opportunity

CIHR-III launched this funding opportunity in December 2008 in partnership with CIHR Knowledge Translation Branch. Its purpose is to strengthen knowledge translation by funding research syntheses related to preparing for, or in responding to, an influenza pandemic.

Catalyst Grant: Pandemic Preparedness (2008-2009)
Funding Opportunity
Funding Decision

The purpose of this funding opportunity that was launched in December 2008 was to provide seed money for researchers in areas where there are still gaps in knowledge and knowledge translation related to pandemic preparedness. Ten investigators received grants under this initiative (Table 5.6.1.10). Many of the funded projects will examine novel antiviral agents or new methods to modulate host defenses to either fight infection or to suppress harmful exaggerated immune responses. See Appendix 3.12 for further details.

Table 5.6.1.10 – Projects Funded under the Catalyst Grant: Pandemic Preparedness (2008-09)
Principal Investigator	Host Institution	Project Title
Bisaillon, Martin	Université de Sherbrooke	Development of a SOFA-ribozyme-based strategy to control the propagation of the influenza virus.
Dimock, Kenneth	University of Ottawa	The role of sialyltransferases in generating influenza receptors
Gaetz, Stephen	York University (Toronto, Ontario)	Understanding Pandemic Preparedness in the Context of the Canadian Homelessness Crisis
Gagnon, Anita	McGill University	Pandemic Flu Preparedness Among Migrants and Host Communities in Thailand
Hirasawa, Kensuke	Memorial University of Newfoundland	In vivo treatment of influenza virus infection with a MEK inhibitor
Kelvin, David	University Health Network (Toronto)	Alleviation of Influenza Induced Immunopathological Events Through Selective Suppression of Kinase Signalling Pathways
Kollmann, Tobias	University of British Columbia	Optimization and Validation of High-throughput Anti-influenza Peptide Immunoassays
Lin, Rongtuan	Jewish General Hospital (Montreal)	Small molecule agonists of the RIG-I pathway as innate stimulatory agents against influenza virus infection
Mubareka, Samira	Sunnybrook Health Sciences Centre	Understanding the role of host factors in human influenza virus transmission
Skowronski, Danuta	University of British Columbia	Sentinel Household Surveillance: Web Platform for Community-based Monitoring and Evaluation during a Pandemic

Catalyst Grant: Vaccines of the 21st Century
Funding Opportunity

Vaccines and immunization programs were strategic research areas identified by the PPRSI Task Group in consultation with stakeholders. The purpose of this funding opportunity, which was announced in December 2008 is to support vaccine research in areas such as better understanding of the human immune response that provides protective immunity, correlates of immune protection, improved animal models for vaccine development, new adjuvants, harnessing the innate immune response, system biology approaches, modes of vaccine administration and regulatory barriers to developing new and improved vaccines. Two applications were funded under this opportunity (Table 5.6.1.11). Drs Gaston De Serres, Danuta Skowronski and Brian Ward will examine the antibody responses to influenza B viral strains in infants and toddlers who were vaccinated with two different strains of influenza B virus in consecutive years in order to determine whether the current influenza vaccination strategy in this population is the most effective. The goal of Dr. Ralph Pantophlet's project is to create an influenza vaccine with broad specificity by designing proteins that contain highly conserved regions of influenza viral proteins and testing them in a vaccine. See Appendix 3.13 for project summaries.

Table 5.6.1.11 – Projects Funded under the Catalyst Grant: Vaccines of the 21st Century
Principal Investigator	Host Institution	Project Title
De Serres, Gaston; Skowronski, Danuta; Ward, Brian	B.C. Centre for Disease Control	TITRE II: TIV Infant/Toddler Response Evaluation (TITRE) – follow-up & focus on influenza B
Pantophlet, Ralph	Simon Fraser University	Immunogen design to elicit broadly neutralizing antibodies to influenza

Operating Grant: Winter 2009 Priority Announcement (Pandemic Preparedness)
Funding Opportunity

This Priority Announcement on the Winter 2009 CIHR Operating Grant competitions offers additional sources of funding for highly rated applications that are relevant to pandemic preparedness and the 2009 pandemic influenza threat. Dr. John Schrader was funded under this opportunity (Table 5.6.1.12). He and his team plan to use a novel Canadian technology to isolate monoclonal antibodies against pandemic H1N1/09 influenza in order to create a new therapeutic candidate for critically ill patients. See Appendix 3.14 for a project summary.

Table 5.6.1.12 – Projects Funded under the Operating Grant: Winter 2009 Priority Announcement (Pandemic Preparedness)
Principal Investigator	Host Institution	Project Title
Schrader, John	The Biomedical Research Centre, Vancouver	A novel Canadian platform to reduce the mortality of novel H1N1 influenza

Catalyst Grant: Pandemic Outbreak Research Response
Funding Opportunity
Funding Decision

In its efforts to mobilize the pandemic influenza research community, CIHR-III announced a new funding opportunity: Catalyst Grant: Pandemic Outbreak Research Response on July 13, 2009. Its aim is to bring together researchers in priority research areas by supporting team planning, development activities and research that will lead to strategies to control the current H1N1 outbreak and contribute to future pandemic planning. The CIHR Institutes of Aboriginal Peoples' Health and Circulatory and Respiratory Health partnered with CIHR-III and will support research that aligns with their mandates. Five successful research teams (Table 5.6.1.13) were funded in October 2009 following an expedited application deadlines and peer review. Much of the research will focus on determining why certain individuals infected with the H1N1 influenza virus develop severe illness and on discovering both clinical and public health interventions that will reduce disease severity. See Appendix 3.15 for project summaries.

Table 5.6.1.13 – Projects Funded under the Catalyst Grant: Pandemic Outbreak Research Response
Principal Investigator	Host Institution	Project Title
Fowler, Robert	Sunnybrook Health Sciences Centre	Influenza-and H1N1-Related Critical Illness – Demand and Capacity in the Health Care System: the Canadian ICU Flu Study
Mcgeer, Allison	Mount Sinai Hospital (Toronto)	Outcomes of Pandemic Influenza in Pregnancy (OPIP)
Schrader, John	University of British Columbia	A novel Canadian platform to reduce the mortality of novel H1N1 influenza
Sharma, Satyendra	University of Manitoba	The mechanism and immunological correlates of severe respiratory illness following 2009 H1N1 pandemic influenza virus infection
Tremblay, Cécile	Centre Hospitalier de l'Université de Montréal (CHUM)	Controlling the Influenza A H1N1 pandemic strain infection: dynamics and mechanisms of innate and adaptive immune responses in a system biology approach

5.6.2 Funding Opportunities Initiated by Others and Summary of Research Supported by the PPSRI

Operating Grants: Partnerships for Health System Improvement
Funding Opportunity
Funding Decision

In the event of a pandemic, many issues will arise that relate to health systems and services. Research is needed to create new knowledge for informed decision making in pandemic planning and policies. To encourage this research, CIHR-III partnered with the CIHR Institutes of Health Services and Policy Research and Population and Public Health to launch this funding opportunity in July 2007. The purpose is to support teams of researchers and decision-makers interested in conducting applied health research in the area of pandemic preparedness useful to health system managers and/or policy makers. Dr. Fawziah Marra at the University of British Columbia and her colleagues will determine whether pharmacists in rural areas in British Columbia can be used to improve vaccination rates in these areas. If this approach is successful, it could easily be adapted to other vaccination programs and other jurisdictions. See Appendix 4.1 for further details.

Bridge Funding: Pandemic Preparedness Strategic Research Initiative
Funding Decision

Bridge funding offers support to researchers who submit excellent research operating grant applications that are not funded through the regular CIHR competition. Three researchers in areas relevant to the PPSRI were awarded bridge funding operating grants in February 2007 (see Table 5.6.2.1). The research that is supported will examine the risk of infection attributable to emergency ward visits, the role of cytokines in the pathogenesis of influenza and the mechanisms involved in long-term protection against influenza infection.

Table 5.6.2.1 – Projects Funded under the Bridge Funding: Pandemic Preparedness Strategic Research Initiative
Principal Investigator	Host Institution	Project Title
Kelvin, David	University Health Network (Toronto)	The role of chemokines and chemokine receptors in the development of host response and immunopathogenesis during H5N1 influenza infections
Quach-Thanh, Caroline	Montreal Children's Hospital	Transmission of infections in health-care settings: Determining the risk of infection in elderly after a visit to the emergency room
Watts, Tania	University of Toronto	Costimulation and maintenance of T cell memory

China-Canada Joint Health Research Initiative – Grants Program
Funding Decision

The program is jointly managed and funded by CIHR and the National Natural Science Foundation of China (NSFC). Its aim is to promote the development of Canadian-Chinese scientific co-operation between universities, hospitals, research institutes or affiliated research organizations in Canada and China through the support of collaborative research grants. One of the twenty successful grants awarded in October 2007 under this program is directly relevant to the strategic priorities of the PPSRI and was supported by the Initiative (Table 5.6.2.2). The successful applicants, Dr. Jingxin Cao and Dr. George Gao, plan to examine why certain forms of avian influenza are highly pathogenic in humans. Their research results will be useful in helping to contain the spread of influenza and in treating humans infected with highly pathogenic forms of the virus. See Appendix 4.2 for a project summary.

Table 5.6.2.2 – Project Funded under the China-Canada Joint Health Research Initiative – Grants Program Funding Opportunity
Principal Investigator	Host Institution	Project Title
Cao, Jingxin and Gao, George	University of Manitoba Chinese Academy of Medical Sciences (Beijing)	Studies on roles of NS1 protein of avian influenza H5N1 virus in evasion of innate and adaptive immunities using an interferon sensitive vaccinia virus recombinant system

Applied Public Health Chairs
Funding opportunity
Funding decision

CIHR Institute of Population and Public Health manages and supports this program in partnership with the PHAC. The goal is to support research in policy and program intervention that has national relevance to public health, to foster links with the public health system, and to educate and mentor public health researchers. Two of the ten successful grants awarded in the July 2007 competition have direct relevance to pandemic preparedness and, therefore, were partially supported by the PPSRI (Table 5.6.2.3). Dr. Manuel plans to evaluate the impact of Ontario's Universal Immunization Program on population health and to create tools that will enable public health planners at all governmental levels estimate the potential of intervention strategies on population health. Dr. Sargeant plans to investigate population-level risk factors and intervention strategies for zoonotic disease by bringing together networks of animal and human health researchers, practitioners and decision makers. This research and the networks established will be essential for pandemic planning and response because pandemic influenza is a zoonotic disease that initially spreads from animal reservoirs, such as birds, to humans. See Appendix 4.3 for project summaries.

Table 5.6.2.3 – Project Funded under the Applied Public Health Chairs Funding Opportunity
Principal Investigator	Host Institution	Project Title
Manuel, Douglas	Sunnybrook Health Sciences Centre	Population health impact intervention assessment tools (PHIIAT)
Sargeant, Janice	University of Guelph	Meeting the zoonotic disease public health challenge: Integrated methodologies for research and application

Team Grant: China-Canada Collaborative Teams in Health Research
Funding Opportunity

CIHR in partnership with the Ministry of Science and Technology of the People's Republic of China announced this funding opportunity in March 2009. Its purpose is to further strengthen health and medical research capacity in treatment and vaccine development for pandemic influenza in both countries. No grants were funded under this opportunity.

Operating Grant: Health Systems Research on H1N1
Funding Opportunity

The CIHR Institute of Population and Public Health (IPPH) led this initiative in partnership with several CIHR institutes and the PHAC. The purpose of this funding opportunity was to support the prompt initiation of research focused on public health and health care system interventions to H1N1 and to study the differential effects of these responses on vulnerable populations. Research was encouraged on the potential ethical, legal and social implications of public health and other health care system interventions directed at the H1N1 outbreak.

6. PPSRI Annual Meeting of Researchers and Knowledge-Users

CIHR and partners plan to organize annual meetings of pandemic and influenza researchers and end-users of the knowledge created. Participants will include researchers funded through the PPSRI, other national and international researchers from university, hospital, government and private research laboratories, heath-care and public health practitioners, program administrators, policy and decision makers and representatives from sponsoring organizations. The meetings will provide an overview of the current state of pandemic and influenza research, build collaboration amongst researchers and linkages to end-users, and support knowledge translation of research findings.

6.1 Canadian Pandemic Preparedness Meeting: From Discovery to Frontlines. Winnipeg, Manitoba, November 6-8, 2008

The first annual PPSRI meeting, entitled: "Canadian Pandemic Preparedness Meeting: From Discovery to Frontlines", was organized and sponsored by CIHR-III, PHAC and CFIA and was held in Winnipeg on November 6-8, 2008. Over 150 influenza and pandemic researchers and stakeholders from across Canada participated in the meeting. The meeting succeeded in bringing people together who would not have done so otherwise, resulting in increased awareness among researchers of each others' work, as well as creating national momentum in pandemic preparedness research.

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. Participants learned about the facility and the research related to pandemic influenza that is being conducted through presentations by CSCHAH researchers.

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.

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 appreciated the opportunity to network and to get to know researchers in different areas. A report summarizing the meeting can be found online.

6.2 Canadian Pandemic Preparedness Meeting: H1N1 Outbreak Research Response. Toronto, Ontario, July 8, 2009

In the summer of 2009, the pandemic H1N1/09 influenza virus was spreading throughout the world. While most infected individuals experienced mild symptoms, a proportion developed severe respiratory symptoms requiring prolonged stays in intensive care units and ventilator support. Intensive care units in countries in the Southern hemisphere were beginning to reach their capacity. There were concerns that increased numbers of cases would overwhelm resources during the 2009 flu season in the Northern hemisphere. There was also the risk that the virus will mutate to become more pathogenic.

Health-care providers and policymakers were under significant pressure to make informed health-care and public health decisions based on scientific information. To facilitate this process, the Canadian Institutes of Health Research (CIHR), Rx&D Health Research Foundation (HRF) and Canadian Food Inspection Agency (CFIA) sponsored a one-day research meeting of more than 180 influenza and pandemic experts from across Canada on July 8, 2009, in Toronto.

The day began with a plenary session in which participants were given an overview of the current pandemic from experts in epidemiology, animal science, ethics, vaccines and immunization and public health. Participants then gathered in smaller groups for workshops focused on specific research areas. The workshops included short presentations on current research results and plans related to the pandemic and provided an opportunity for participants to discuss research needs and ways to work together. The meeting closed with an open forum plenary session in which critical aspects of Canada's research response were discussed. A report summarizing the meeting can be found online.

7. Midterm Evaluation of PPSRI

In an effort to continually improve its strategic programs, CIHR-III contracted Natalie Kishchuk Research and Evaluation Inc. to carry out a midterm evaluation of the PPSRI. Information from several sources was compiled and analyzed in order to assess the design and progress of the Initiative up to March 2009.

Overall the mid-term evaluation of PPSRI was favourable. For example the evaluator found that PPSRI priority setting was effective in identifying pandemic research priorities that were inclusive, widely endorsed, and quickly translated into funding opportunities. As of March 2009, PPSRI supported an estimated 150 trainees, thereby building research capacity in pandemic preparedness. Development workshops and meetings organized by CIHR increased awareness of the Initiative and research findings. The number of applications received in some of the priority areas, particularly those concerning public health measures and knowledge translation opportunities, was low. In future initiatives, novel promotion strategies will be developed to increase application rates.

The evaluator concluded that the PPSRI was successful in stimulating targeted research that will improve Canada's influenza pandemic preparedness. The evaluation report can be found online.

8. Summary

Significant progress has been made by CIHR-III and partners in developing a research initiative to build research capacity and to prepare for and respond to a pandemic influenza. Successful applicants to the first funding opportunity for pandemic preparedness operating grants in June 2006 were announced in February 2007, and critical research projects are underway. The PPSRI Task Group worked with stakeholders over the summer of 2006 to quickly set strategic research priorities that have formed the basis of a second major round of funding opportunities for pandemic preparedness research in December 2006. To enhance the funding available for these grants, the CIHR-III approached and reached agreements with partners that have a mutual interest in influenza pandemic preparedness. Collaboration with the PHAC led to the launch of a third major set of funding opportunities in the fall of 2007, and has allowed the PPSRI to enter a second important phase: supporting team leaders and individuals in their preparations for outbreak research. CIHR-III and PHAC has also established an influenza research network consisting of researchers from across the country that are developing and testing methodologies to evaluate influenza vaccine safety and effectiveness and are establishing methods for vaccine program implementation. In addition, the international research collaborations supported through the International Opportunities Program, Team Grants and the PPSRI Annual Meetings are enhancing linkages between Canadian and international researchers. This is important because the threat of an influenza pandemic is global. The research capacity and expertise that was created by the PPSRI was critical in facilitating the research response to the H1N1/09 influenza pandemic. It is anticipated that the results from research that has been fostered and supported by the PPSRI and the continued activities of the Initiative will have significant outcomes that will help Canada and the rest of the world prepare for both seasonal influenza and future influenza pandemics.

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