Breakthrough in bird flu quest
Thursday February 02, 2006 11:03 - (SA)
PARIS - Scientists say they have crafted a revolutionary vaccine that in tests on lab mice offers the hope of thwarting an influenza pandemic sparked by H5N1 bird flu.
If confirmed as safe and effective for humans, the vaccine could also be manufactured swiftly and in large quantities, making it ideal for stockpiling in the event of a pandemic, they say.
The problem with present flu vaccines is that they stimulate the immune system against specific sub-types of influenza strains.
However, these sub-types are a shifting target - they mutate into forms that evade the vaccines.
Most times, the mutation is a slight and relatively innocuous drift, but occasionally it can be a genetic leap which transforms the virus into a vicious new foe against which humans have no immunity.
This remote risk is what drives the present scare: the fear that the H5N1 virus, which at the moment can kill humans but is not transmissible between individuals, picks up genes that makes it highly contagious as well as lethal.
The mutation problem means it is usually pointless to try to devise a pandemic vaccine before the killer strain erupts.
The profile of the killer strain would be little more than a guess, and precious resources would be wasted if the bet proves wrong.
But Indian-born scientists working in the United States believe they have taken a giant step towards hitting the H5N1 virus across a range of sub-types.
In a report published online by the British health journal The Lancet, the team describe how they took an adenovirus - the virus that causes the common cold - and engineered it to produce a protein called haemagglutinin (HA).
HA is a spike-like protein on the surface of a flu virus that helps the microbe to attach itself to a cell prior to entering it and hijacking it.
In this case, the HA produced by the adenovirus appears to be common across the range of H5N1 sub-types.
Mice were injected with the engineered vaccine or alternatively with a harmless saline solution, and then exposed to high levels of two types of H5N1, found among people who fell sick in Hong Kong in 2003 and in Vietnam in 2004.
The modified adenovirus "gave 100-percent protection," said one of the co-authors, Suryaprakash Sambhara of the US Centres for Disease Control and Prevention (CDC).
"Among immunised animals, there was minimum body weight loss, sickness and morbidity...(and) there were no side effects," he said in a phone interview.
Vaccines typically prime antibodies, the foot soldiers of the immune system, into recognising a pathogen, or part of it.
If the intruder enters the body, antibodies swarm over it.
However, the adenovirus stimulated a very low antibody response.
Instead, it works by activating the heavy artillery - a type of white blood cell called CD8 T cells.
A long road lies ahead of refining the prototype vaccine, testing it further on lab animals and then, if everything works out, cautiously giving it to human volunteers to assess that it is safe and effective.
But Sambhara said current findings suggest that by attacking the H5N1 on a part of its genome that is less prone to mutate, the vaccine was aiming at a fixed target, not a moving one.
Asked if the vaccine would shield humans in the event of an H5N1 pandemic, he replied, "It should, it should. It should also protect there, too."
Almost as exciting, he said, was that the engineered vaccine could be manufactured in a culture in a matter of days.
At present, vaccines are usually grown in eggs, a process that takes six months - a timescale that could put millions of people at risk if a pandemic does occur.
"The population at risk is about 1.2 billion people, according to the WHO [World Health Organisation], so you are looking at some four to six billion eggs, and we don't have the manufacturing facilities for this," said Sambhara.
In addition, avian flu is lethal for chickens, which could make it hard to get the eggs in the first places, he said.
"The beauty of this approach is that we can use it for stockpiling" vaccines ahead of any outbreak, he said.
There other flu strains that are different from the H5 strain, and which could in the future also threaten a pandemic.
However, Sambhara said that by getting an adenovirus vaccine to express internal proteins that are common to all flu virus strains, the hope was, one day, for a "universal" shield against all forms of influenza.
Sapa-AFP
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