Bird flu: kick-start vaccination or face the consequences

Bird flu: kick-start vaccination or face the consequences

* 14 October 2005
* From New Scientist Print Edition
* Debora Mackenzie
* Kristin Choo

SUDDENLY, the threat of avian flu is getting some serious attention in the US. Representatives of 80 countries met in Washington DC last week to discuss strategies to contain outbreaks of the virus.

Meanwhile Michael Leavitt, US Secretary of Health and Human Services, this week made his first official trip to Asia to encourage leaders in the region to do more to stop the virus spreading. And a decision by the US senate to earmark an extra $4 billion to protect the country against a flu pandemic is awaiting approval by the House of Representatives.

These moves are welcome, but do not go far enough, flu experts say. Substantial commercial, political and bureaucratic barriers remain that will stop us being able to vaccinate enough of the world's people to contain any pandemic. What is urgently required is a global plan to combat the threat.
“Because the virus is new to our immune systems, people will need two injections. That halves the number we can protect”

The problem boils down to numbers. A hybrid vaccine virus has already been produced that could immunise people against the H5N1 bird flu virus. But manufacturers can't make enough of it. Production capacity will not significantly increase any time soon, beyond a few new plants already under construction in Europe, and with the equipment available they can make only a few kilograms of the viral protein that forms the basis of the vaccine. If each dose contains 15 micrograms (ìg) of viral protein, as in vaccines against ordinary flu, that's enough for no more than 900 million doses of vaccine over a normal six-month production cycle (New Scientist, 28 February 2004, p 36).

But that doesn't mean 900 million people can be protected. Because H5N1 is new to our immune system, people will need two vaccinations a few weeks apart. That halves the number who can be protected within six months to 450 million.

And even that is likely to be wildly optimistic. "This virus has done a number on us," says Robert Webster of St Jude Children's Research Hospital in Memphis, Tennessee. In August, human trials of the hybrid vaccine showed that each person would require two 90-ìg doses. That equates to enough vaccine worldwide for 75 million people, or around one quarter the US population.

The way round this, say vaccine experts, is to boost the power of the shots by combining them with a simple immunity-stimulating chemical called an adjuvant. Norbert Hehme at vaccine maker GlaxoSmithKline in Dresden, Germany, has made a vaccine that can induce full immunity against relatives of the H5 family of bird flu viruses with two doses of just 1.9 ìg each.

Given existing production capacity for H5N1, this would allow 3.5 billion people to be protected. That is as many as could practically be immunised, given other limitations, says David Fedson, founder of the vaccine industry's pandemic task force. But the US trials did not use adjuvant, despite warnings that without it only large doses would work (New Scientist, 26 March, p 10).

Trials of adjuvant with doses down to 7.5 ìg have begun in Australia and Hungary, and are planned in Canada, the US and Japan. But no one is looking at the smaller doses that would be needed to stretch the available vaccine as far as it needs to go.

"By not determining the lowest dose that is acceptably immunogenic, the vaccine companies have shown they do not understand the unforgiving arithmetic of pandemic vaccine supply," Fedson told New Scientist. "That means millions will not receive vaccine, and thousands will die. Economists call this an opportunity cost. I call it a tragedy."

Commercial considerations are also getting in the way. Companies have not yet worked out how to share patented techniques for making the vaccines, and are reluctant to start human trials on vaccines that have no guaranteed market. "If we have purchase guarantees from governments, that changes things," says Bram Palache of the Belgian-based vaccine maker Solvay. The US, UK and France, among others, have placed such orders in the past few months, which is why trials are now starting, But the constraints on vaccine production mean these orders may never be fulfilled.

There are political obstacles too. Nearly 70 per cent of the world's vaccine manufacturing capacity is in five countries in western Europe, and virus expert Albert Osterhaus of Erasmus University in Rotterdam, the Netherlands, predicts these countries will be reluctant to allow vaccine to be exported until their own populations are immunised.

Fedson, however, believes these barriers can be overcome. What is needed, he argues, is a well-funded international body along the lines of the Global Fund to Fight AIDS, Tuberculosis and Malaria, launched by the UN in 2002, which has spent $3 billion tackling these diseases. A similar body for pandemic flu, Fedson says, could coordinate vaccine development and fund the testing that will get us the low-dose, adjuvanted vaccine that may be needed to fight a global pandemic. "Wouldn't it be horrible if a pandemic comes and afterwards we discover we could have made far more vaccine?" he says. "We'll look like fools."

Such a body could also head off the political crisis that would ensue if vaccine-manufacturing countries decide to immunise their own people before allowing vaccine to be exported. "Can you imagine the conflict that would result if people in Bordeaux get vaccinated and people in Barcelona don't?" says Fedson. By paying into a global collaboration, he says, the "have-not" countries could ensure that they will get a share of vaccines made elsewhere.

Something has to give soon. Last week, there were renewed fears that H5N1 had infected birds in Turkey and Romania. As New Scientist went to press, experts could only say that the virus in Turkey might be from the H5 family, while it is unclear what pathogen caused the infection in Romania. But the world is getting increasingly nervous that the virus, or one like it, will sooner or later evolve into a form that can be passed readily between people.

If that were to happen, the first wave of infection would spread round the world in weeks. After three months, it would most likely die down, giving manufacturers breathing space to identify the exact strain and produce vaccine to contain a second wave.

Yet, if the political will were there, we could already be taking steps to protect ourselves against the first wave. When researchers at the vaccine maker Chiron tested the blood of people who had received an experimental vaccine against a 1997 strain of H5 bird flu, they found it cross-reacted strongly with the H5 flu that killed people in Vietnam last year. This raises hopes that a vaccine against 2004 or even 1997 H5, say, might work against an H5 pandemic strain, even if it differs slightly.
“Millions will not receive vaccine, thousands will die. Economists call this an opportunity cost. I call it a tragedy”

"We are confident that a vaccine is feasible even if it is not fully matched to the pandemic strain, as long as there is a strong adjuvant," Giuseppe del Giudice of Chiron told New Scientist. While it may not protect 100 per cent, it might mean that H5 does not kill so many people. And it would act as a "priming" dose, meaning people would later require only one shot of vaccine matched to the pandemic strain.

The science is in place. Now the world needs to push forward to test and license a vaccine. When pandemic fears surfaced with swine flu in 1976, the US government developed, tested and licensed a vaccine, then made enough for most of its people, within six months. "We did it in 1976," says Fedson. "Why can't we do it now?"

From issue 2521 of New Scientist magazine, 14 October 2005, page 6

http://www.newscientist.com/article.ns?id=mg18825215.900