Influenza team at the Wellcome Trust

In response to the unfolding events surrounding H5N1 'avian' influenza since 2001 and more recently the unfolding pandemic due to swine-origin H1N1 influenza, the Trust has been working with UK and international partners to improve understanding and develop policy responses to these diseases. A snapshot of our activities is provided below:

"The UK research response to pandemic H1N1 2009: Key results and implications for policy makers", Wellcome Trust, London, 18 July 2011
In 2009, BBSRC, Department for Environment, Food and Rural Affairs (Defra), MRC and Wellcome Trust invested £7.5 million in a series of joint research projects designed to improve our understanding of the emerging H1N1 influenza pandemic virus and how it spreads. On 18 July 2011, a meeting was hosted at the Trust to disseminate to stakeholders how the outputs of the projects have increased our knowledge of pandemic influenza; to demonstrate the value of establishing multidisciplinary research and funder consortia; to discuss policy implications of the research; and to capture lessons learned by researchers and funders. Presentations from the Combating Swine Influenza (COSI) initiative, Mechanisms of Severe Acute Influenza Consortium (MOSAIC) and FluWatch were complemented by a keynote address from the Health Protection Agency entitled "Translating research into public health practice: influenza pandemics" and a final panel discussion to summarise key results and implications for policy makers.

Genomics of Influenza Meeting: Wellcome Trust, London, 28-29 March 2011

Mortality caused by pandemic influenza has been an evolutionary selective force in human populations for perhaps 500 years; however, the nature of this selection and the genes involved are unknown. An expert working group recently met at the Wellcome Trust in London to review epidemiological and immunological evidence bearing on the host genomics of severe influenza infection. This meeting was funded predominantly by a small grant from the Trust's Medical Humanities programme with further support from the Wellcome Trust’s Influenza Team.

Paul Kellam from the Sanger Centre spoke on the co-evolution of host and virus as an increasing competition between organisms. Dennis Shanks from the University of Queensland in Australia described the mortality risk factors in military units during the 1918–19 influenza pandemic. Kenneth Baillie from the Roslin Institute detailed observations on severely ill patients during the 2009 influenza pandemic. Peter Horby of the Wellcome Trust unit in Hanoi, Vietnam, described the cumulative toll of zoonotic H5H1 influenza infections (with a low infection rate but extraordinary mortality) in South-east Asia. Tracy Hussell from Imperial College spoke on the plastic nature of the pulmonary immune response and how previous infections condition the lungs’ response. Michael Parker from Oxford University discussed ethical issues associated with obtaining genomic samples. Peter Parham from Stanford University in the USA described the interaction of the HLA and KIR genes in lymphocytes and the likelihood that infectious diseases had shaped this part of the human genome. Finally, Dennis Shanks described unique epidemiological patterns of infectious diseases outbreaks on small Pacific Islands and the potential to use descendents of such special populations to answer questions regarding mortality risk factors during the 1918–19 influenza pandemic.

Two major topics suitable for further research emerged during the discussions: historical epidemiologic studies concerning the 1918–19 influenza pandemic, and detailed virus and host genomic studies from those who were severely ill during the 2009 pandemic or from avian H5N1 infection. Several major aspects of the 1918–19 pandemic remain unexplained, such as the unusual increased mortality in otherwise healthy adults and the devastating mortality of up to 20 per cent of the population that occurred in isolated human populations such as the Pacific Islands. The very unevenness of influenza mortality during 1918 is puzzling and suggests that host, viral and environmental factors were at work in unknown proportions. Although the 2009 pandemic influenza virus was related to the 1918 virus, the clinical outcomes differed markedly in terms of the frequency of severe illness; however, during 2009, a number of extremely ill patients filled intensive care units. Although some of the patients in 2009 had known risk factors (such as pregnancy or immunosuppression induced by medication), otherwise healthy adults were also admitted to intensive care units with severe viral pneumonia, without any obvious risk factors. Genomic samples saved during the pandemic and from H5N1 patients are available for study to determine whether there are detectable host genetic risk factors. Given more epidemiological and genomic work, it may be possible to define genetic risk factors for severe illness during pandemic or zoonotic influenza.

Prepared by Professor Dennis Shanks (University of Queensland) and reviewed by T Sutherland, F Hayden and E Shaw (Wellcome Trust).

Satellite workshop meeting at Pacific Health Summit: 24 June 2010
The Wellcome Trust Influenza Research Team held a satellite workshop meeting at the Pacific Health Summit 2010 to review the team's activities and those of its partners in the context of the 2009 H1N1 pandemic and to discuss implementation of the recently posted World Health Organization Public Health Research Agenda for Influenza. As many of the team's activities have been conducted in collaboration with organisations in the UK and other countries, the meeting also provided an opportunity to hear from the colleagues working in these partners of the Trust, particularly from those in the World Health Organization. Report of meeting [Word 232KB]

Mechanisms of lung injury and immunomodulator interventions in influenza meeting: 21 March 2010 (California)
The Trust has been working with colleagues at BARDA and other US governmental agencies to organise a joint meeting on the mechanisms of lung injury and possible value of immunomodulator therapies. This workshop reviewed current understanding of lung injury in acute influenza and described cellular and molecular mechanisms of lung injury that are common to influenza and other pathogens. In addition, therapeutic agents that target host response proteins and pathways were identified and investigational agents in development were reviewed.

Pandemic H1N1 2009 influenza studies in the UK

Human based studies
In response to the recent H1N1 pandemic declared by the World Health Organization, the Wellcome Trust, the Department of Health and the Medical Research Council (MRC) convened a meeting to develop priorities for maximising the research potential of the evolving pandemic in the UK. There was a strong consensus for clinical cohort studies in order to assess both severe hospitalised influenza infections and mild to moderate influenza infections occurring in the community.Consortia bids were developed proposing research addressing hospitalised and community infections, including vaccine and non-pharmaceutical intervention studies.
Workshop on Pandemic Clinical Research meeting report [PDF 1.08MB]

Animal based studies
The Veterinary Laboratories Agency convened a meeting with UK funding bodies (Wellcome Trust, MRC, Department for Environment, Food and Rural Affairs and the Biotechnology and Biological Sciences Research Council) at the Trust to prioritise strategies to study the novel swine-origin H1N1 virus in swine. Urgent research questions were identified, including the impact and consequences of spread of the novel swine-origin H1N1 virus in swine populations. Collaborative consortia bids were developed leading to funding of the Combating Swine Influenza (COSI) initiative.
Workshop on pandemic H1N1 research in swine [PDF 48.5KB]

Working with the WHO

Pandemic influenza preparedness plans
The Wellcome Trust supported a WHO study to evaluate national pandemic preparedness plans and to determine national and regional states of preparedness across WHO member states at the start of the influenza A(H1N1) 2009 pandemic.

Comparative analysis of national pandemic influenza preparedness plans [PDF 2.67MB], World Health Organization, Geneva, Switzerland, January 2011

Vaccines for pandemic H5N1 and pandemic threats
The Trust is working with the WHO's expert advisory group on vaccination, Strategic Advisory Group of Experts (SAGE), to develop recommendations for the use of 'inter-pandemic' influenza vaccines.
SAGE recommendations on the use of licensed human H5N1 influenza vaccines in the interpandemic period [PDF 508KB]
Full report [PDF 1.4MB]

Paper produced by the Trust to inform SAGE: Evans D et al. “Prepandemic” immunization for novel influenza viruses, “swine flu” vaccine, Guillain-Barré Syndrome, and the Detection of Rare Severe Adverse Events. J Infec Dis 2009;200:321-328.

New vaccine technologies
The Trust assisted the WHO in its latest annual meeting to discuss progress with H5N1 vaccine development.
Report of the 5th meeting on the evaluation of pandemic influenza prototype vaccines in clinical trials: World Health Organization, Geneva, Switzerland, 12-13 February 2009 [PDF 192KB]

The Trust and the WHO's Initiative for Vaccine Research (IVR) jointly organised the 4th Meeting on Influenza Vaccines that Induce Broad Spectrum and Long-lasting Immune Responses, at the Wellcome Trust in London, 9-10 November 2009.

The Trust is also helping to support the 6th Meeting on Evaluation of Pandemic Influenza Vaccines in Clinical Trials, Geneva, Switzerland, 18-19 February 2010.

Developing an influenza road map

With its international partners, the Trust is developing a research 'road map' to examine research gaps to improve scientific understanding of influenza - in the areas of vaccines and prevention; therapeutics and disease pathology; and population sciences.
First meeting of the Influenza Scientific Advisory Group - executive summary [PDF 116KB]

Convalescent plasma and Ig-based therapies for influenza treatment meeting

On 7 September 2009, the Wellcome Trust held a meeting of experts from the scientific and clinical communities to discuss and explore possibilities for conducting a trial of convalescent plasma and/or immunoglobulin (Ig)-based therapies in the near term for seriously ill patients hospitalized with pandemic H1N1 illness. The idea for this proposal came from observations in both the 1918 pandemic and during the H5N1 ('bird flu') outbreak indicating that convalescent blood product treatment seems to improve patient survival.
Report of the plasma therapy meeting [PDF 60KB]

Biomedicine Forum 2008

In preparation for a 'high level' discussion event on Pandemic Influenza in November 2008, the Trust produced a background briefing presentation to inform participants.
Biomedicine Forum briefing [PDF 2.18MB]