October 2001

Study Seeks to Determine Effectiveness of Diluted Smallpox Vaccine

As concerns increase about the use of biological agents in acts of terrorism or war, federal health agencies are evaluating existing measures and stepping up new ones to protect the public from the health consequences of such an attack. The National Institute of Allergy and Infectious Diseases (NIAID), a component of the U.S. National Institutes of Health (NIH), supports research on the diagnosis, prevention and treatment of infections caused by microbes with potential for use as biological weapons.

Smallpox virus (Variola major) is considered one of the most dangerous potential biological weapons because it is easily transmitted from person to person and few people carry full immunity to the virus. Although a worldwide immunization program eradicated smallpox disease decades ago, small quantities of smallpox virus still exist in a few research laboratories around the world.

NIAID research on smallpox focuses on extending existing vaccine stocks to increase the number of available doses, developing new vaccines and treatments, as well as diagnostic tools to detect the disease quickly.

With smallpox eradicated, vaccinations against the disease have not been required in the United States since 1972. Those who did receive a vaccination may have little immunity to the virus left, and people born in the United States since that time have not been vaccinated at all. No new smallpox vaccine has been manufactured in almost 20 years.

Will a Diluted Vaccine Protect?

Last year, an NIAID study examined volunteers' skin and immune-system responses to a 1:10 dilution or a 1:100 dilution of the off-the-shelf Dryvax vaccine. They compared those responses to those from other volunteers who had received the full-strength vaccine. The results showed not only that the full-strength vaccine had maintained its potency, but also that the majority of people who received a single dose of the 1:10 dilution developed a sore at the injection site and antibodies in their blood. Even though the 1:10 vaccine dilution was capable of stimulating an immune response in most people in the study, it was not likely to protect enough people in a large population to sufficiently stop spread of smallpox.

Based on those results, a new study is underway to determine if a diluted vaccine combined with an alternative vaccination schedule would protect a greater number of people than did the standard dose and regimen. The study, which will enroll no more than 684 people, is evaluating three different doses of Dryvax. Sixteen percent of the participants will receive the full-strength formulation. About one-third of the volunteers will receive a 1:5 diluted vaccine, and about half the volunteers will receive a vaccine that has been diluted 1:10.

Researchers will study the ability of the various vaccine dilutions to stimulate a scab, or "take," at the injection site and produce antibodies in the blood. If participants haven't developed a scab in seven to nine days after vaccination, they will be revaccinated with the same vaccine they received the first time. By that strategy, researchers hope to learn which vaccine dose given in a single injection elicits the best response among the largest number of people and whether "boosters" can fortify the immune response in those who didn't react to the first injection.

Where the Study is Taking Place

• St. Louis University, St. Louis, Missouri
• Baylor College of Medicine, Houston, Texas
• University of Maryland, Baltimore, Maryland
• University of Rochester, Rochester, New York

The study is currently scheduled to begin in November and will last about two-and-a-half months. During that time, volunteers will make 16 visits to the study clinic. Voluteers must be between the ages of 18 and 32.

The Dryvax vaccine, produced by Wyeth Laboratories, consists of vaccinia (cowpox) virus, which is related to the smallpox virus. The vaccine causes a very mild infection resulting in immunity to smallpox and only rarely causes visible symptoms other than the characteristic scab at the injection site.

View the study details here (or search www.ClinicalTrials.gov).

For more information about the study, please telephone 1-866-624-8296, ext. 224.

NIAID is a component of the National Institutes of Health (NIH), which is an agency of the Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, illness from potential agents of bioterrorism, tuberculosis, malaria, autoimmune disorders, asthma and allergies.

News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

Prepared by:
Office of Communications and Public Liaison
National Institute of Allergy and Infectious Diseases
National Institutes of Health
Bethesda, MD 20892

Department of Health and Human Services

National Institutes of Health (NIH) Bethesda, Maryland 20892

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