Improved version appears not to carry risk of encephalitis

By Bill Scanlon, Rocky Mountain News
November 15, 2002

The smallpox vaccine being readied for the American population in case of a bioterrorism attack is less likely to cause encephalitis and other major complications than earlier vaccines, animal tests indicate.

"Our vaccine should be safer," said Thomas Monath, chief science officer at Cambridge, Mass.-based Acambis, which won a government contract to produce 195 million doses.

Acambis officials described the vaccine, ACAM 1000, to the annual meeting of the American Society of Tropical Medicine & Hygiene in Denver on Thursday.

Acambis bases its vaccine on the old, reliable New York Health Department smallpox vaccine, Dryvax - which many baby boomers received as children - except the new vaccine is produced in a cell culture, not in calfskin.

ACAM 1000 will be a seventh-generation clone of Dryvax, purified, filtered and tested against the presence of numerous other accidental viruses.

The goal is to create a vaccine similar to Dryvax, with its reliability, but with much fewer complications.

One side effect of Dryvax was that it caused encephalitis, a serious swelling in the brain, in about three of every 1 million Americans vaccinated.

In recent tests, Acambis scientists injected the old and new vaccine into the brains of mice. Three of the six mice injected with the old Dryvax died, but none of the six injected with the new ACAM 1000 died, Monath said.

"There's no way to tell for sure until you've tested a lot of human subjects," Monath said. "But with previous smallpox vaccines, complications in humans closely mimicked complications in animals."

Animals also were less likely to develop edema or meningitis with the new vaccine, he said.

The vaccine is from a live virus, so it still poses a small risk. Vaccines could be made safer - such as using just the DNA of the virus - but their effectiveness has been disappointing.

The world's scientists thought they had rid the globe of smallpox in the 1970s when the last of the outbreaks were squelched by vaccines.

But Americans were shocked in 1998 when a Russian defector said his country had weaponized smallpox. Now, the world's leaders worry that ruble-starved Russian scientists may have sold some of that weaponized smallpox to regimes such as Iraq or to terrorists.

Symptoms of smallpox, one of history's deadliest diseases, include fever, headache, diarrhea, a rash that turns to lesions, excessive bleeding and delirium.

The Bush administration is considering whether to call on all Americans to be vaccinated before a smallpox bioterrorism attack or to stockpile the vaccine and deliver it on hours notice to the site of an outbreak.

If they choose the latter, there are about a dozen sites around the country that will store "push packages" of vaccine ready to arrive anywhere in the United States within 12 hours.

Within 24 or 36 hours, the National Pharmacy Stockpile would deliver more of the specific vaccine to the outbreak site.

The vaccine triggers antibodies that take a few days to develop and protect the body against smallpox. The virus itself takes a couple of weeks to be symptomatic, so public health officials think that inoculating people even four days after an outbreak would offer some protection.

In Colorado and elsewhere, local health departments would administer the vaccines.

The federal government this year awarded slightly more than $1 billion to health departments and hospitals to boost bioterrorism preparedness.The United States was uninterested in the bioterrorism risk until the late 1990s, when President Clinton read a novel about bioterrorism, said Jim Hughes, director of the National Center of Infectious Diseases.

Clinton pushed for a smallpox vaccine, but only small companies, such as Acambis, bid on the project because money was lacking. It wasn't until after Sept. 11 that bioterrorism became a national security issue, and with that came the money that spurred the large pharmaceutical companies to get involved.

Acambis joined with pharmaceutical giant Baxter when the federal government asked for another 155 million doses. Acambis' vaccine should be ready to use sometime next year, Monath said. Total cost: about $650 million.

Listen to Bill Scanlon at 8 a.m. today on "The State of Colorado" on KNRC-AM (1510).