A universal soldier against all flu strains? Researchers seek a vaccine to target the stable M2e protein which has been common to flu viruses since the first one was isolated in 1933

February 28, 2006

Brussels, Feb 2006

One way to beat viruses is to knock them out with antiviral drugs. Another is to vaccinate against them beforehand. While this may work for some, such as measles and mumps, others, like influenza, are proving far trickier to pin down. Until recently, scientists thought it was impossible to develop broad-acting flu vaccines. But one EU-funded project, Universal Vaccine, is on track to proving them wrong.

One of the biggest challenges facing scientists in the search for better influenza vaccines is trying to keep up with the virus' tendency to mutate – the bigger the mutation the more potentially lethal the results. Major flu pandemics hitting the world in the past century, such as the 1968 Hong Kong strain, are usually the result of a major mutation.

The next big change – leaving our immune defences and pharmaceutical armoury behind – might be around the corner. Scientists worry that the H5N1 strain, currently infecting birds across Asia and now spreading into Europe and elsewhere, will mix (or 'reassort') with a human variety in someone who is infected with both flu types. Another slim possibility is it will mix in another host capable of being infected with both human and avian influenza, such as pigs.

But the emphasis is on 'slim', suggests scientist and lecturer Kristine Van Reeth of the Faculty of Veterinary Medicine at Gent University, Belgium. "Luckily, though, it is difficult for one type of virus to jump from one species to another – and each usually only affects a particular type of animal – what is happening in Asia [with the avian flu virus] is unusual," she recently told European journalists attending a Commission-hosted press briefing on pandemic and avian flu. Van Reeth is involved in a follow-up EU-funded project, called ESNIP 2, which is a network monitoring influenza in pigs and includes labs in Europe, the USA and Hong Kong.

It's all in the protein

Attempts at synthesising a universal vaccination for all human flu strains have been held back by the nature of the virus. The two proteins at work ('H' for haemagglutinin and 'N' for neuraminidase) determine the virus subtypes: 16 different Hs (H1-H16) and nine Ns (N1-N9). But there is also a smaller third protein, called M2 which has, until now, remained in the scientific sidelines. Vaccine development has traditionally focused on blocking H and N, but the Universal Vaccine team are targeting a part of the M2 protein (M2e) which, analysis showed, has remained relatively constant since the influenza virus was first isolated in 1933.

The Belgian, Swedish, Dutch and English scientists in the €1.2 million EU-funded project are now developing a broad-spectrum vaccine against all influenza A subtypes using M2e as their target. The Belgians, working out of the Flanders Interuniversity Institute for Biotechnology (VIB) in Gent, have already found that an M2e-based vaccine protects mice against what they call a "potentially lethal influenza challenge". They added an adjuvant (antigens which boost the impact) and the protection was stronger again. Toxicity screening also came out positive.

Within the Universal Vaccine project, the Europeans hope to proceed to human trials with their vaccine as early as 2007. If successful, they are quietly confident that a universal vaccine could provide life-long immunity against the virus and provide far greater protection in the event of a pandemic. "It may even help to eradicate the disease in humans," the team note in a press statement.

The European Union has long supported research into avian and pandemic influenza, dating back to some €6 million set aside for projects in the Fifth Framework Programme (FP5) for research, which ran from 1998-2002. In the current FP6, €16 million was budgeted for such research, from which the Universal Vaccine project is being funded. Earlier this year, the Commission announced it had made a further €20 million available for research in this important field.

DG Research
http:///europa.eu.int/comm/dgs/research/i ndex_en.html
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