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

J Infect Dis. 2007 Mar 15;195(6):826-32. doi: 10.1086/511828. Epub 2007 Feb 5.

Abstract

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.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Allantois / virology
  • Animals
  • Antibodies, Viral / blood
  • Antibody Formation
  • Chick Embryo
  • Chorion / virology
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Smallpox Vaccine / adverse effects
  • Smallpox Vaccine / therapeutic use*
  • Treatment Outcome
  • Variola virus / isolation & purification
  • Variola virus / physiology

Substances

  • Antibodies, Viral
  • Smallpox Vaccine