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Vaccines get a shot in the arm

Denver firms make them old, new ways

By Jim Erickson, News Science Writer

At Colorado Serum's north Denver plant, workers churn out hundreds of thousands of doses of the nation's only veterinary anthrax vaccine each year, using the same decades-old technique the Russians are believed to use in their human vaccine.

A few miles away, a fledgling vaccine company called GlobeImmune just built a production facility at the Fitzsimons Bioscience Park. GlobeImmune plans to start making an AIDS vaccine by the end of the year and will also seek federal funding to develop a new anthrax vaccine using recombinant DNA technology.

Long neglected by pharmaceutical companies, vaccines became a hot topic when the anthrax-letter attacks hit. Now the nation's top health officials are pushing for increased production of the scarce human anthrax vaccine, and Congress is negotiating a package that could provide more than $3 billion for bioterrorism defenses, including new vaccines.

The two Denver companies -- one founded in 1923 and the other in 2001 -- highlight the differences between traditional, time-tested vaccine-production techniques and the new wave of "second generation" approaches that have been touted in recent weeks.

"We have a technology for making a better version of the anthrax vaccine or even improving the present vaccine but up until mid-September, there wasn't any reason to do it," said Richard C. Duke, president of GlobeImmune.

Colorado Serum has been making livestock anthrax vaccine the same way since 1957, using live spores of a weakened, non-pathogenic strain of the bacteria called the Sterne strain. Each 20-drop dose of the Colorado Serum vaccine contains 2 million or more live anthrax spores that trigger a protective immune response in animals, said Dr. Michael Piontkowski, the company's senior staff veterinarian.

The Sterne strain was discovered in the 1930s by South African scientist Max Sterne. Colorado Serum got some, and many researchers believe the Russians use the same strain in their human anthrax vaccine, Piontkowski said.

In an emergency, the Colorado Serum veterinary vaccine could be used on people but would probably cause serious side effects, he said. And besides, it would make more sense to treat victims of a mass anthrax attack with antibiotics such as Cipro, he said.

The Colorado Serum live-spore vaccine takes two weeks to become effective.

"Let's just say, for instance, there was a massive release of anthrax today in Denver. Would it do you any good to go ahead and vaccinate yourself with our vaccine?" Piontkowski said.

"Probably not. Because, as you've seen with these outbreaks in other parts of the United States, generally in two weeks the situation is over."

U.S. Health and Human Services Secretary Tommy Thompson said last month that the nation's only manufacturer of human anthrax vaccine, BioPort Corp. of Lansing, Mich., could be providing vaccine to the military by Thanksgiving.

But BioPort stopped distributing its vaccine after failing Food and Drug Administration inspections in 1999 and 2000, and it still lacks FDA approval. Federal inspectors will visit the facility in mid-December.

The BioPort vaccine doesn't use live spores or bacteria. Instead, toxins produced by the bacteria are deactivated, mixed with a fluid and injected. The inoculated person develops antibodies to the deactivated toxins.

About 500,000 of the 2.4 million troops the Pentagon wanted to inoculate received the BioPort vaccine before the program was suspended. Some vaccinated soldiers have complained that it causes chronic fatigue, bone and joint pain, memory loss and other problems.

Some service personnel refused to receive the injections because of the side effects.

"If you check the Web sites on this vaccine, there are obviously a lot of people who say that this vaccine did them harm," GlobeImmune's Duke said.

"And I don't know how well documented any of that is, but it seems to me that we could use a vaccine that has fewer side effects."

Next month, the Defense Department is expected to issue a call to scientists for new bioterrorism defenses, including vaccines. Duke said GlobeImmune will seek funding to study the feasibility of making a new anthrax vaccine using the same technology the company uses on its HIV vaccine.

Yeast, the lowly microbe that makes bread rise and gives champagne its sparkle, is the key to the new AIDS vaccine being developed by GlobeImmune.

In the May edition of the journal Nature Medicine, the Denver scientists said they inserted genes from HIV, the virus that causes AIDS, into yeast cells. Then they injected the modified yeast cells directly into laboratory mice.

The yeast vaccine prompted a strong immune response that killed infected cells in mice, Duke said. The company hopes to enter human trials with the HIV vaccine in mid-2002, he said.

The same idea could be used to make a new anthrax vaccine, he said.

Anthrax genes could be inserted into yeast cells, which would act as tiny molecular factories to crank out millions of copies of a deactivated anthrax toxin. Then the yeast cells, carrying the deactivated toxin, would be injected as a vaccine.

"You use the yeast as factories to make lots and lots of the protein, and then you actually use the whole yeast as the vaccine," Duke said. "The yeast acts as the delivery vehicle."

The technique has the potential to quickly produce large amounts of vaccine that is 99.9 percent pure, Duke said. Because it's so pure, the genetically engineered yeast vaccine would have fewer side effects than the relatively crude BioPort vaccine, he said.

The BioPort vaccine requires six shots over 18 months. The promising but still nonexistent yeast vaccine might be able to cut the number of shots in half, Duke said.

The technique could even be used to create vaccines that protect against several bioterror agents -- say anthrax, plague, tularemia and botulism toxin -- simultaneously, he said.

 

Contact Jim Erickson at (303) 892-5129 or ericksonj@RockyMountainNews.com.

November 23, 2001

ALL INFORMATION, DATA, AND MATERIAL CONTAINED, PRESENTED, OR PROVIDED HERE IS FOR GENERAL INFORMATION PURPOSES ONLY AND IS NOT TO BE CONSTRUED AS REFLECTING THE KNOWLEDGE OR OPINIONS OF THE PUBLISHER, AND IS NOT TO BE CONSTRUED OR INTENDED AS PROVIDING MEDICAL OR LEGAL ADVICE.  THE DECISION WHETHER OR NOT TO VACCINATE IS AN IMPORTANT AND COMPLEX ISSUE AND SHOULD BE MADE BY YOU, AND YOU ALONE, IN CONSULTATION WITH YOUR HEALTH CARE PROVIDER.