To stretch and strengthen vaccines, scientists use adjuvants but the H5N1 threat means more powerful adjuvants are needed. Claire O'Connell reports
The current outbreak of avian flu may have the world on tenterhooks, but there is an upside: the threat of a pandemic has given vaccine research a shot in the arm, which could help develop tools to fight other infections.
If the avian flu virus H5N1 adapts to spreading easily between humans, it could spark a global flu pandemic and, based on current figures, vaccine manufacturers will be caught short.
According to the World Health Organisation (WHO), it will take three-six months from the start of a pandemic to begin large-scale commercial production of an appropriate vaccine.
Optimistic estimates predict the world's flu-vaccine plants would take six months to produce vaccine for less than 10 per cent of the human population.
To stretch the available vaccine rations, scientists will use adjuvants, which are compounds that render vaccines more effective in the body. It's a trick that has been in use for almost 100 years, says Dr Ed Lavelle, head of the adjuvant research group at Trinity College Dublin's school of biochemistry and immunology.
Many purified vaccines dissipate quickly when injected by themselves, but an adjuvant, or helper, keeps the vaccine in the body for longer and helps to stimulate the production of antibodies or other defence mechanisms in the body, says Lavelle.
The most widely used adjuvant is a gel of aluminium salts known as alum.
It is cheap to produce, has an excellent safety record and is the only adjuvant currently approved for human use in the United States.
However, according to Lavelle, alum is not the most potent adjuvant, and its prevalence means that other, more effective adjuvants may be left unused because manufacturers don't want the expense of jumping regulatory hurdles.
Now, though, the need for more powerful adjuvants may prompt a bolder approach.
"In some ways what's going on with H5N1 is great for adjuvant research because people realise we need potent adjuvants and have started talking about them," says Lavelle, who lists a wide range of potential commercial adjuvants such as plant lectins, biodegradable microspheres and fat-based carriers.
Some vaccine developers are still using alum to boost H5N1 vaccines in clinical trials, but US company Chiron recently reported success from trials using low doses of its experimental H5N1 vaccine along with MF59, a fat-based adjuvant that is already used with some European commercial flu vaccines.
Chiron's experimental vaccine/adjuvant formulation also appears to protect against slightly different forms of the avian virus, which could potentially render the vaccine more effective in a human pandemic.
Lavelle hopes the wake-up call for adjuvant research will help put in place the tools for dealing effectively with other diseases in the future.
"Even if H5N1 doesn't break out, it's a warning - can you really afford to have just one widely accepted adjuvant that maybe isn't the ideal one?
"There should be a battery of safe and effective adjuvants on a shelf, so if something breaks out, we are ready to go rather than having to go through huge regulatory approvals and clinical trials for the adjuvant as well as the vaccine," he says.
Lavelle's own research looks at using adjuvants for vaccines delivered into the nose or gut.
Live or killed vaccines come naturally packaged with their own adjuvants that stimulate the immune system, but newer, purified vaccines need added adjuvants to bump up the immune response, he explains.
His group has looked at the adjuvant properties of detoxified molecules from E. coli and from the bacterium that causes cholera.
"The idea is to use an adjuvant that will give you a specific response without the toxic side effects," he says, noting that they have studied the adjuvant-aided delivery of experimental vaccines against meningitis B, TB and malaria.
In particular, they look at how adjuvants interact with immune-responsive cells known as dendritic cells to activate different components of the immune system.
"If we can understand precisely what adjuvants are doing to dendritic cells, you can probably design better and safer versions," says Lavell. "The ideal is to have as much control as you can over what an adjuvant is going to do to the vaccine in terms of getting the response that you want."
Lavelle notes that modern lifestyle and travel practices mean we are being exposed to more disease-causing agents, and that the human race will have to continue to deal with emerging infections.
"Most of the time it probably won't be a major problem, but it's not a good idea to be complacent."