Reducing the Dose of Smallpox Vaccine Reduces Vaccine-Associated Morbidity without Reducing Vaccination Success Rates or Immune Responses

Background. When the decision was made to prepare for a deliberate release of smallpox, the United States had ∼15 million doses of Wyeth Dryvax vaccine, which was known to induce significant morbidity when used undiluted; Sanofi Pasteur, Inc., later identified ∼85 million additional doses in storage. Methods. Eleven vaccine-dose groups, each with 30 vaccinia-naive subjects, were given diluted Dryvax vaccine or 1 of 2 lots of Sanofi Pasteur smallpox vaccine and were evaluated for vaccination success rates, morbidity, and immune responses. Results. Estimated doses of 106.6–C108.2 pfu of virus/mL induced major reactions (or “takes”) in 93%–100% of subjects in each dose group. No differences in vaccination take rates, lesion size, erythema, and induration or in serum neutralizing-antibody response were detected between the groups. However, systemic reactogenicity and missed activities were significantly lower for the vaccine groups given doses of 106.6–C107.2 pfu/mL than for those given doses of 106.6–C108.2 pfu/mL. Conclusions. These findings support the use of a higher dilution of Wyeth Dryvax vaccine and Sanofi Pasteur smallpox vaccine, given that the resulting morbidity should be significantly lower without loss of vaccine effectiveness. A plan for use of higher dilutions would create an enormous stockpile of vaccine.