Current status of smallpox vaccine.

To the Editor: The possible use of smallpox virus as a weapon by terrorists has stimulated growing international concern and led to a recent review by the World Health Organization of the global availability of smallpox vaccine. This review found approximately 60 million doses worldwide, with little current vaccine manufacture, although limited vaccine seed remains available (1). Ongoing discussions in the United States suggest that the national stockpile should contain at least 40 million doses to be held in reserve for emergency use, including in case of a terrorist release of smallpox virus (OToole, this issue, pp. 540-6). The current U.S. stockpile contains approximately 15.4 million doses of vaccinia vaccine (Dryvax) made from the New York City Board of Health strain of vaccinia and was produced by Wyeth Laboratories in 13 separate lots. The vaccine is lyophylized in glass vials with rubber stoppers and sealed with a metal band. When rehydrated, each vial contains 100 doses and has a potency of at least 108 plaque-forming units (pfu)/ml. Some vials of the vaccine stockpile have shown elevated moisture levels and thus failed routine quality control testing; however, the vaccine in these vials remains potent, and the failed lots have not been discarded. The diluent used to rehydrate the vaccine contains brilliant green, which makes the vaccine easier to visualize when administered with bifurcated needles. Over time, the brilliant green has deteriorated, and most of the available diluent does not pass quality control. Discussions are under way with Wyeth to begin production of sufficient new diluent for the entire stockpile. The vaccine is administered by superficial inoculation (scarification) with a bifurcated needle. Fewer than 1 million bifurcated needles are held as part of the stockpile. As with the diluent, Wyeth has been requested to produce additional bifurcated needles. Vaccinia virus produces adverse reactions in a small percentage of vaccinated persons. Adverse reactions are treated with vaccinia immune globulin (VIG), currently only available from Baxter Healthcare Corporation (5,400 vials of VIG in stock). Each vial contains 5 ml of VIG; the recommended dose for postvaccine complications is 0.6 ml per kg of body weight. This volume is sufficient to treat adverse reactions in approximately 675 adults. Further, the entire stockpile of VIG has been placed on hold while the cause of a slight pink discoloration is investigated. Until the cause of the discoloration is determined or another approved supply of VIG is obtained, no vaccinia vaccine is being released. While unknown, the rate of adverse reactions in todays population is likely to be greater than seen during the global eradication campaign because of recent increases in the number of immunocompromised persons. The Department of Defense has recently contracted the processing of new lots of VIG (to be administered intravenously rather than by the intramuscular route like existing VIG stocks); however, maintaining adequate stocks of VIG will remain a challenge. In the event of release of smallpox virus, persons at high risk and persons exposed but not yet showing clinical illness would be vaccinated immediately. Intensive case detection and vaccination of contacts and other persons at risk would follow. All vaccine, including lots retained after failed quality control tests, would be made available for emergency use. Previous studies have found that more than 90% of susceptible persons respond to vaccinia virus with a titer of 107 pocks/ml (2). In an emergency, consideration would be given to diluting the existing vaccine as much as 10-fold, so that each vial could conceivably contain 1,000 doses of vaccine, rather than the current 100 doses. The present vaccine container is sufficiently large to accommodate the added diluent. The absence of sufficient quantities of VIG to protect against adverse reactions during a mass immunization campaign would necessitate careful screening of those receiving the vaccine; some persons with adverse reactions would likely go untreated. While the intentional release of smallpox virus would represent a global emergency, the existing national stockpile could be effectively used to limit the spread of disease and buy time while the pharmaceutical industry begins emergency vaccine production.