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Fusion #5A:Fusion #5 13/11/07 09:32 Page 1 Fusion #5a:Fusion #5 13/11/07 09:32 Page 1 fusion 5 Fusion #5a:Fusion #5 13/11/07 09:32 Page 2 12 / FUSION . MICHAELMAS 2006 Bird flu vaccines and reverse genetics Influenza is rightly perceived as a significant health risk, and the spread of H5N1 (bird flu) has provoked alarm as it spreads across the globe. The groups of Professor George Brownlee, FRS and Ervin Fodor have for the past decade been working on understanding the molecular mechanisms underlying the influenza virus replication and adaptation from one species to another. Here, post-doctoral researcher Dr Ruth Harvey explains their approach. Influenza virus was first isolated in 1933, and it ion channel activity required by the virus for the still remains a public health and economic problem release of its RNA into the host cell, but today. Since its isolation there have been two resistance to this class of drugs is very common. Influenza virus binding to major pandemics, ‘Asian flu’ in 1957 (H2N2 The new neuraminidase inhibitors (such as infected cell via subtype) and ‘Hong Kong’ flu in 1968 (H3N2 Relenza and Tamiflu) block release of new virus Haemagglutinin spikes on subtype), estimated to have killed a total of 1.5 particles from infected cells, but these drugs virus surface. million people. But we should not forget the only work if administered in the first 72 hours infamous ‘Spanish flu’ in 1918 (H1N1 subtype) after infection and there have also been reports that reportedly killed an estimated 20 to 40 million of resistance starting to emerge. We still need people. By contrast the current outbreak of ‘Bird more effective drugs or a better vaccine that flu’ has to date infected around 200 people with would be effective against any strain of virus. about 100 deaths since the first case in 1997. Influenza research at the Dunn School by The occurrence of influenza virus each year, and George Brownlee, Ervin Fodor and others led to the recommendation for annual vaccination of at the development of the reverse genetics system risk groups, such as the elderly or that allows the construction of ‘designer’ immunocompromised, is the result of antigenic viruses from potentially any combination of the drift – the ability of the virus, as with many RNA virus genome segments. This is a huge step viruses, to mutate rapidly. There is however a form forward for the manufacture of vaccine strains, of more drastic genetic change, caused when allowing vaccine candidates to be made that segments of two viruses from different sources re- are, for example, antigenically relevant in a high assort in a single cell. This is known as antigenic growth background. This new reverse genetics shift and essentially gives rise to a new sub-type system has been used to create a non- THE SIR WILLIAM DUNN of virus. Pandemics often follow such a shift. pathogenic seed vaccine against the H5N1 bird SCHOOL OF PATHOLOGY flu virus. The UK government plan now includes is a department of the University of Oxford The current vaccine used worldwide is a trivalent the manufacture of H5N1 vaccine from such a website: vaccine. Each year, the World Health Organisation seed stock if pandemic bird flu occurs in the UK. www.path.ox.ac.uk (WHO) predicts the influenza strains, (A – H1 Contacts: and H3 subtype and B) likely to circulate the Currently both Prof Brownlee’s group and Dr Professor Herman following year based on epidemiological data Fodor’s group focus on fundamental work, Waldmann, FRS collected worldwide. The three virus strains are attempting to elucidate the molecular mechanisms Head of Department Sir William Dunn School grown in chicken’s eggs and from these stocks of transcription and replication of the influenza of Pathology, a vaccine is prepared. The vaccine requires updating virus genomic RNA, the structure and function of South Parks Road each year and so there is a very tight time frame the virus RNA polymerase, and the involvement Oxford OX1 3RE for first deciding which strains to include and then of the polymerase in the adaptation of avian email: herman.waldmann@ path.ox.ac.uk producing the vaccines. This process means that influenza to mammalian cells. This research should there is always a chance that the viruses included in lead to a better understanding of how the virus Dr Eric Sidebottom the vaccine will be out of date by the time the works and why the function of the polymerase is Sir William Dunn School of Pathology, vaccine is administered, although the viruses are so essential for the virus. Such an understanding South Parks Road normally similar enough to give sufficient protection may lead to new drugs targeted to viral or host Oxford OX1 3RE against any new antigenically drifted strains. proteins. Such drugs would complement those Tel: (44) (0)1865 285751 email: eric.sidebottom@ presently available, and increase our ability to path.ox.ac.uk Two groups of drugs are used for the treatment combat the threat of any emerging influenza of influenza. Amantadine/rimantadine block an viruses, including bird flu. Fusion #5a:Fusion #5 13/11/07 09:32 Page 3 fusionTHE NEWSLETTER OF THE SIR WILLIAM DUNN SCHOOL OF PATHOLOGY ISSUE 5 . MICHAELMAS 2006 Contents Editorial 1 Editorial News 2 The department continues to thrive scientifically against a background of escalating Siamon Gordon costs and taxation for access to University services. Lab Reunion 4 This is reflected in the expanson of 5 year the pressure on departments such as ours by Research Profile 6 programme grants which now total 11 on an enabling the overheads that are raised on annual basis. We are pleased to welcome Prof grants to provide support to the scientific Research Notes 7 Oreste Acuto who has joined us from the infrastructure rather than be consumed by the Dunn School Joins Pasteur Institute, and provides for the salary costs. With the Milstein Chair the Dunn European Drive for School will have five endowed Chairs and three community an expertise in cell signalling which New Cancer will create many opportunities for understanding externally funded senior appointments Therapies 8 how interactions with ligands outside of cells (Wellcome PRF, MRC Professorship and an MRC can be transmitted to changes within. This area Senior Scientists). With the advent of Full Development News 9 of research has broad relevance in areas of local Economic Costing, externally funded research ranging from Immunology, Cancer Cell appointments and endowed postitions are likely Size Matters 10 Biology to Cardiovascular Disease. The departure to be the longer-term salvation of departments NEW Faces 11 of Prof Jeffrey Errrington to head a major such as ours. Needless to say we will be seeking further endowed positions to maximize our microbiology initiative at Newcastle University Bird Flu Vaccines and has inspired an energetic search to find new financial viability. Reverse Genetics 12 leadership in the area of Microbiology, and we hope that this appointment will be completed in Finally, our congratulations to William James and the not-too distant future. Our hope is to use Quentin Sattentau for being awarded the Title this appointment to provide a nidus for the of Distinction of Professor, and to Nigel resurgence of British microbiology, and this will Saunders and Shona Murphy to Readerships. certainly be facilitated by the very powerful immunology groupings within the department Herman Waldmann, FRS, Head of Department whose research efforts interface closely with microbial pathogenesis. Our fundraising efforts for the Cesar Milstein Chair in Cancer Research have now taken us to the £2m mark, leaving us just £0.7m off our target. We are sorry to have lost our Development Officer Susan Harrison who has now taken on a significant role as Head of Development at Lincoln college. I am pleased however that she continues to help us complete the fundraising for this important Chair. Not only do such endowed Chairs enable Oxford to attract star quality scientists, they also ease Siamon Gordon Fusion #5a:Fusion #5 13/11/07 09:32 Page 4 2 / FUSION . MICHAELMAS 2006 News Awards Grants Professor Herman Waldmann has been awarded Two major grants to support work on the Mary Tyler Moore and Dr S. Robert Levine microbicides in the department have been Excellence in Clinical Research Award by the awarded over the past few months. Juvenile Diabetes Research Foundation (JRDF). The award, made jointly to Dr Lucienne Dr William James has been awarded a Chatenoud, Prof J F Bach and Prof. Waldmann, programme grant by the US NIH to use the recognizes the contribution made to the Envaptin technology originating in his laboratory treatment of diabetes by the anti-CD3 antibody to develop microbicides targeting multiple developed by Herman Waldmann and Geoff Hale sexually transmitted infections. The award, at the Dunn School. totalling more than $3.5m, involves laboratories at the University of California, Los Angeles, and Another member of the Dunn School has been Leuven, Belgium in a concerted drive to take elected to the Royal Society. Professor Nicholas Envaptins from the laboratory to preclinical trials. Proudfoot, Brownlee-Abraham Professor of The aim is to isolate Envaptins targeting Herpes Molecular Biology, was elected in May 2005, Simplex virus Type 2 and Human Papilloma virus with the citation recognizing his pioneering work Type 16, to complement those targeting HIV, on polyadenylation and transcriptional already isolated by William James, and to put termination which has had a major impact on them through a development program involving current knowledge of the mechanism and control lead identification, medicinal chemistry of mRNA processing. refinement, formulation and ex vivo testing. The aim is to be able to offer a single preparation Prizes that will simultaneously protect against infection Marianna Papaspyridonos, from Dr David Greaves by multiple infectious agents.
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