Reducing the dose of smallpox vaccine reduces vaccine-associated morbidity without reducing vaccination success rates or immune responses.

Journal Article (Journal Article;Multicenter Study)

BACKGROUND: When the decision was made to prepare for a deliberate release of smallpox, the United States had approximately 15 million doses of Wyeth Dryvax vaccine, which was known to induce significant morbidity when used undiluted; Sanofi Pasteur, Inc., later identified approximately 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 10(6.6)-10(8.2) 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 10(6.6)-10(7.2) pfu/mL than for those given doses of 10(7.6)-10(8.2) 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.

Full Text

Duke Authors

Cited Authors

  • Couch, RB; Winokur, P; Edwards, KM; Black, S; Atmar, RL; Stapleton, JT; Kissner, JM; Shinefield, H; Denny, TN; Bybel, MJ; Newman, FK; Yan, L; National Institute of Allergy and Infectious Diseases Smallpox Vaccine Study Group,

Published Date

  • March 15, 2007

Published In

Volume / Issue

  • 195 / 6

Start / End Page

  • 826 - 832

PubMed ID

  • 17299712

International Standard Serial Number (ISSN)

  • 0022-1899

Digital Object Identifier (DOI)

  • 10.1086/511828


  • eng

Conference Location

  • United States