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 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.
Couch
Robert B
RB
Baylor College of Medicine, Houston, TX, 77030, USA.
Winokur
Patricia
P
Edwards
Kathryn M
KM
Black
Steven
S
Atmar
Robert L
RL
Stapleton
Jack T
JT
Kissner
Jennifer M
JM
Shinefield
Henry
H
Denny
Thomas N
TN
Bybel
Michael J
MJ
Newman
Frances K
FK
Yan
Lihan
L
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
D000914:Antibodies, Viral; D012900:Smallpox Vaccine