Jury still out on vaccines

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bird fluBANGKOK, 8 December (IRIN) - International pharmaceutical companies are racing to prepare, and obtain regulatory approval for, a vaccine to protect humans against avian influenza, but scientists do not know whether the vaccines under development would be able to protect people from a potential pandemic influenza strain, if it eventually emerges.

At present, 27 human clinical trials of vaccines against several different strains of avian influenza are under way by more than a dozen western drug companies, and so far, they have resulted in some immune response in those vaccinated.

However, the vaccines now in development are based on strains of the lethal H5N1 virus that have circulated in Vietnam, Indonesia and Turkey and influenzas are fast mutating viruses, so it is unclear whether vaccines developed from old strains will offer any protection against new strains.

"You have to keep up with the virus," Linda Lambert, chief of the respiratory diseases branch of the United States National Institute of Health, said at a recent conference on vaccines in Bangkok. "If I use the vaccine for 2004, will I protect against the virus that is circulating in 2005, 2006 or 2007?

"With flu, you don't know when you are ahead and when you are behind," she added. "We have to pick something and get vaccine manufacturers to make it. People are now spending a lot of money on vaccines without knowing how useful they are going to be against 2006, 2007 and 2008 strains."

Lambert also said scientists did not know whether the immune response provoked by a single vaccination would be adequate to fully protect people from the virulent disease - and some studies suggest two doses may be necessary, further straining production capacity.

"Everybody after a first dose [of the vaccine] gets some immune response," she said. "What nobody can tell you is what level of anti-bodies you need to prevent infection, severe illness or death."

These problems are merely some of the many challenges confronting scientists and public health specialists as they struggle to prepare a vaccine - and adequate vaccine production capacity – to protect the world's population in case the current virus evolves into a form easily transmissible from person to person.

Avian influenza, a disease primarily infecting birds, has so far wiped out large swathes of poultry across Asia, Africa and parts of Europe. But the virus has also infected about 258 people, 60 per cent of whom died.

While most of the people infected appear to have contracted the virus directly from exposure to ailing birds, public health specialists fear the virus could mutate into a form easily transmissible between humans, potentially triggering a virulent global influenza pandemic such as the Spanish Flu of 1914.

Yet the campaign to prepare a vaccine faces many scientific, logistical and public health challenges, including a serious shortage of vaccine production capacity, and tricky questions about when to use a potential vaccine.

Public health professionals say that advocating a pre-pandemic vaccination campaign carries risks if the vaccination causes some adverse reactions that could undermine public confidence in future vaccinations once a pandemic actually broke out.

In 1976, for example, millions of Americans were vaccinated against a feared swine flu epidemic that never materialised. But the vaccination was believed to have caused several hundred people to fall ill with a rare neurological disease that left them paralysed.

"You need to be cautious about immunising on a large scale when there is no human disease in the population," said David Wood, coordinator for the quality, safety and standards team of the World Health Organization's department of immunisation. "You have to weigh the potential risks. The jury is still out."

Studies have suggested that vaccines based on older bird flu strains could offer some, limited 'cross-protection' against newer strains of the virus, even if they did not have the same efficacy as a vaccine matched exactly to the pandemic strain of the virus.

Given that it could take four to six months to produce the first large quantities of vaccine against a new pandemic strain, David Salisbury, director of immunisation of the UK's Department of Health, believes public health specialists should consider pre-pandemic vaccinations – using pre-prepared vaccines - if it appeared a pandemic was indeed imminent.

"Even if poorly matched against the pandemic strain, they may play a valuable role in minimising disease, reducing transmission, and even aborting a pandemic," he said.

Salisbury argued that a post pandemic-vaccine, which is produced after the pandemic is identified, "is actually going to do remarkably little at protecting anybody, given manufacturers' inability to produce significant quantities of a vaccine soon after the onset of a pandemic.

"A delay of four months from the start of a global pandemic would mean that the initial epidemic would be largely over by the time most of the model populations had been vaccinated," he added. "However, our results indicated that even a 20 percent stockpile of pre-prepared vaccine could have a substantial effect on attack rates - even if its efficacy was less than a vaccine matched against the pandemic strain."

Several countries have already ordered, or are in negotiations for, a stock-pile of pre-pandemic vaccines to give some protection to health workers, fire fighters, police and other essential service providers if a pandemic appears imminent. However, Salisbury said schoolchildren should also be among those receiving pre-pandemic vaccinations, since they have one of the highest influenza transmission rates.

He also argued that a pre-pandemic vaccination campaign could help reduce pressure on vaccine production capacity after a pandemic begins, since many people would have already received some protection "if there is a good match between pre- and post-pandemic strains".

At present, drug companies have a combined capacity to annually produce about 350 million doses of seasonal influenza vaccines, though experts estimate that production could be boosted to 500 million doses if manufacturers optimise output, by scaling up production to work round the clock.

Given rising market demand for annual flu shots in developed countries, companies are planning to invest in production facilities that would allow them within two to three years to be able to produce an additional 280 million doses, bringing total capacity to 780 million doses.

Seasonal flu vaccines are also generally designed to protect recipients against three separate flu strains each year, which means they require greater facilities for producing three different types of so-called 'antigens', which are what trigger the immune response. But if a pandemic strain of avian influenza arose, scientists could potentially produce 2.3 billion doses of a vaccine that would protect exclusively against that single strain of the virus.

This capacity would still be far short of the requirements to protect all the world's 6.7 billion people, especially since studies suggest people may require two doses of the vaccine for full protection.

To further boost vaccination-making capacity, drug companies are urging public health specialists and governments to encourage more people to take annual flu shots, which would give companies the incentive to invest in new facilities. "Increasing seasonal use of influenza vaccines could help the industry scale up capacity to be better prepared in case of a pandemic," Alejandro Costa, of the World Health Organisation, told the conference.

source - Reuters