Dr. Kathryn Edwards is leading the smallpox vaccine trial at VUMC. Edwards and colleagues will begin enrolling participants in the trial. (photo by Dana Johnson)
Vanderbilt tests smallpox vaccine to protect nation
Vanderbilt has been awarded a $12.6 million National Institutes of Health contract to conduct clinical trials and test new vaccines, including a smallpox vaccine to help prepare the nation for a possible bioterrorism attack.
Because of the national sense of urgency and concern over a possible smallpox bioterrorism attack, a clinical trial testing the current stockpile of smallpox vaccine will soon begin and may hold the key to providing protection for the entire U.S. population — more than 283 million.
“Smallpox will be our initial target in preparing for the bioterrorism threat,” explained Dr. Kathryn Edwards, principal investigator of the clinical trials and professor of Pediatrics in the division of Pediatric Infectious Diseases.
The smallpox vaccine consists of a weakened pox virus strain. The current stockpile of smallpox vaccine, Dryvax, kept by the Centers for Disease Control and Prevention, is enough to immunize 15 million people. An additional 75 million doses were found in October (frozen for 30 years) by the manufacturer, Aventis Pasteur (AP). These doses were produced for the Department of Defense and stored at AP. The Vanderbilt clinical trials will determine if the frozen vaccine remains effective and safe to use. Routine smallpox vaccination ended in 1971.
The clinical trials will be conducted at Vanderbilt, the University of Iowa, Northern California Kaiser Permanente and Baylor College of Medicine. The trials will consist of vaccinating more than 300 healthy adults, 18-32 years of age, who have never received a smallpox vaccine. Three different doses of vaccines will be tested: full-strength, diluted five times, and diluted 10 times. These tests will determine how much the vaccine can be diluted and still be effective. If shown to be effective at its weakest dilution, a total of 750 million people could be vaccinated with the stockpile if a smallpox outbreak occurred.
Previous research at other sites has shown that Dryvax, the vaccine stored in the CDC stockpile, can be reconstituted with a sterile water-based diluent to a 1-to-10 ratio and still protect more than 97 percent of the volunteers after a single dose of vaccine. Diluting the vaccine to a 1-to-5 ratio produced a 99 percent success rate after one dose of vaccine.
In March, U.S. Secretary of Health and Human Services Tommy Thompson announced that the United States contracted with Illinois-based Baxter International and the British firm Acambis to purchase 155 million doses of a new smallpox vaccine. Acambis already has a $422 million contract with the United States to produce 54 million doses of smallpox vaccine. These products are the next generation of smallpox vaccine using modern cell culture manufacturing processes. But those doses are not readily available and will have to undergo the same vaccine testing before they are released. The doses are expected to be ready in 2003.
“Combined, these 286 million doses will give us enough vaccine to cover every man, woman and child in America by the end of the year,” Thompson said. “And if the Aventis product is shown to be usable, we will be in even stronger stead.”
Vanderbilt will begin enrolling participants in the smallpox trials very soon.
“We are looking for 75 to 100 individuals to participate in the clinical trials,” Edwards said. “They will all be screened to ensure they have no medical conditions and are not at high risk for adverse reactions to the vaccine.”
Edwards said careful screening will be important because the vaccine should cause a blister-like response on the skin where the shot is given, indicating the vaccine is working. The blister will have to stay covered, and the individual must restrict contact with anyone who has a low immune system because they could expose others to the vaccine virus, even though the risk is low.
Participants will be followed for eight visits within the first two months and then telephoned at six months after receiving the vaccine. Volunteers will be compensated for their time and travel. Enrollment will close before the end of July. Once the smallpox trials are over, Edwards said attention will turn to testing other vaccines. It is anticipated that some of these vaccines would include improved versions of the anthrax vaccine.
If you are interested in participating in the smallpox virus vaccine study, call 615-343-8288.