title: Reducing the dose of smallpox vaccine reduces vaccine-associated morbidity without reducing vaccination success rates or immune responses.
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.
authors.affiliation: Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Couch
authors.forename: Patricia
authors.initials: P
authors.lastname: Winokur
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Edwards
authors.forename: Steven
authors.initials: S
authors.lastname: Black
authors.forename: Robert L
authors.initials: RL
authors.lastname: Atmar
authors.forename: Jack T
authors.initials: JT
authors.lastname: Stapleton
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Kissner
authors.forename: Henry
authors.initials: H
authors.lastname: Shinefield
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Denny
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bybel
authors.forename: Frances K
authors.initials: FK
authors.lastname: Newman
authors.forename: Lihan
authors.initials: L
authors.lastname: Yan
mesh_terms: D000293:Adolescent; D000328:Adult; D000482:Allantois / Q000821:virology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D002642:Chick Embryo; D002823:Chorion / Q000821:virology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D012900:Smallpox Vaccine / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D012901:Variola virus / Q000302:isolation & purification / Q000502:physiology
chemical_list: D000914:Antibodies, Viral; D012900:Smallpox Vaccine