Irish work on a safer inoculation has earned attention in the US, writes Dick Ahlstrom
Smallpox looms large in the minds of health and security officials fearful of a bioterrorist attack. Nobody is vaccinated against the virus any more, as it was thought to have been eliminated by 1980.
Governments around the world, including the Republic's, began stockpiling doses of smallpox vaccine after the September 11th attacks on New York and Washington DC.
The US government decided to vaccinate all front-line medical, security and military staff and considered a national vaccination programme.
Fresh research also got under way to try to find safer alternatives to the vaccine, which can cause serious side effects in one in every 1,250 people - and death to one in 20,000.
Now researchers at Trinity College in Dublin and Imperial College London believe they may have come up with a safer smallpox vaccine. They have patented their discovery, and officials in President Bush's National Security Advisory Committee are assessing the work.
The vaccine used against smallpox for decades is based on cowpox, or vaccinia. It is very similar to smallpox and gives immunity against the disease but is much less harmful, although not without risk to those who receive it.
Prof Luke O'Neill of Trinity's department of biochemistry began looking into a safer form of vaccinia in the late 1990s. "It started about three or four years ago, when we were trawling through the vaccinia genome," he says.
He joined with Dr Andrew Bowie of Trinity and a team from Imperial College led by Prof Geoff Smith to see how vaccinia could be made less dangerous. "We were interested in vaccinia because it has all kinds of tricks up its sleeve to dampen down our immune system," says O'Neill.
The team discovered an unknown gene, termed A52R, that blocks the body's immune response to the virus. They then discovered a second gene with a similar action, both acting to block a key defensive response to viral invasion known as the Toll-like receptors.
"The virus switches off the Toll-like receptors, which are an early warning system for the immune system," says O'Neill.
The team genetically engineered the virus, knocking out the A52R gene. Tests showed that it greatly weakened the virus but retained its usefulness in stimulating a strong anti-smallpox response from the immune system. Other versions of the virus were produced, one knocking out the other gene associated with the Toll-like receptors and another in which both of the genes were removed.
The work was important enough to reach publication last month in the Journal Of Experimental Medicine. The new vaccinia forms are very likely to be less toxic, as they don't affect the Toll-like receptors, and are therefore important new candidate vaccines for smallpox.
The work has sparked a great deal of interest in the US, says O'Neill. "Because of the smallpox threat, the US is on the lookout for a weaker form of the virus."
O'Neill got in touch with Dr Joshua Lederberg of the US National Security Advisory Committee, who expressed considerable interest in the new virus. Lederberg, who won the Nobel Prize in Medicine in 1958, at the age of 33, is studying the research, assessing it with 25 other vaccinia forms thought to be safer than existing strains.
O'Neill is very optimistic about being able to use the Trinity-Imperial form in a new, safer vaccine.
The work was supported financially by the Health Research Board, the National Pharmaceutical Biotechnology Centre at Trinity and Science Foundation Ireland. "We are very excited at the prospect of our virus being used to protect against smallpox," says O'Neill.