In view of growing concern over threats of bioterrorism, particularly an outbreak of smallpox, the National Institute of Allergy and Infectious Disease of the US National Institutes of Health is sponsoring a clinical trial of the effectiveness of diluting existing smallpox vaccine.

Routine vaccination against smallpox (Variola major), deemed eradicated worldwide in the 1970s, stopped in the USA in 1972. People immunised before then are now believed to have little, if any, immunity left. Although the vaccine has not been manufactured in nearly 20 years, the government is now seeking enough vaccine to immunise every American. But because new vaccines are not expected to be available until next year, scientists are investigating whether the government's stockpile could be diluted for wider use.

About 15 million doses of the Dryvax vaccine, produced by Wyeth Laboratories, are on hand. The vaccine, which is made from vaccinia (cowpox) virus, creates a very mild infection that causes a characteristic scab at the site of the injection, and results in immunity to smallpox. The 2·5-month trial is designed to determine whether dilutions of the vaccine and an altered vaccination strategy can provide effective immunity, such that the existing supply would be sufficient to deal with an outbreak.

Four sites are involved in the trial: Baylor College of Medicine (Houston, TX), St Louis University, University of Maryland, and University of Rochester (NY). 684 adults will be randomly assigned to receive a full-strength formulation of the vaccine, or a 1-to-5 or 1-to-10 dilution. Participants who do not develop a scab at the injection site or produce antibodies in the blood 7-9 days after vaccination will be revaccinated with the same formulation they received initially. Trial participants must be healthy adults aged 18-32 years who have not been vaccinated against smallpox nor had the disease.

John Treanor, an investigator at the University of Rochester, said recruitment at his site had been somewhat slower than anticipated, perhaps because volunteers must commit to many study visits. But he expects enrolment to be concluded by the end of November, with preliminary results available by the end of the year. He said the vaccine's "take rate", indicated by the formation of an initial blister at the injection site, followed by scarring, is highly correlated with the development of antibodies and the cytotoxic T lymphocyte response. Therefore, the take rate should give a good indication of the effectiveness of the dilutions.