Vaccination success rate and reaction profile with diluted and undiluted smallpox vaccine: a randomized controlled trial.
BACKGROUND
Additional smallpox vaccine doses are needed to augment current US national stockpile. Aventis Pasteur smallpox vaccine (APSV), initially manufactured in the 1950s from the New York Board of Health vaccinia strain in a frozen preparation, appears as effective as lyophilized vaccine but the effectiveness of diluted doses of APSV is unclear.


OBJECTIVE
To compare the vaccination success rate and the reaction profile of various APSV dilutions.


METHODS
A double-blind, randomized controlled trial of 340 healthy vaccinia-naive adults aged 18 to 32 years from 3 academic medical centers who were vaccinated with 1 of 3 strengths of APSV dilutions (undiluted, 1:5, and 1:10) between October 9, 2002, and February 24, 2003. Volunteers were followed up every 3 to 5 days until the vaccination site healed for bandage changes, vaccine response assessment, and adverse event evaluation, followed by 1- and 2-month clinic evaluations and 6-month telephone interview.


METHODS
Successful vaccination, defined by presence of a vesicle or pustule at the inoculation site 6 to 11 days postvaccination, and local and systemic reactions to vaccination.


RESULTS
A total of 340 volunteers were vaccinated (vaccine dose: undiluted, n = 113; 1:5 dilution, n = 114; and 1:10 dilution, n = 113). Following vaccination, 99.4% (95% confidence interval [CI], 97.9%-99.9%) of all volunteers had successful vaccinations. Success rates did not differ between the dilution groups (undiluted, 100.0%; 95% CI, 96.8%-100.0%; 1:5 dilution, 98.2%; 95% CI, 93.8%-99.8%; 1:10 dilution, 100.0% 95% CI, 96.8%-100.0%; P =.33). Overall, 99.7% of volunteers reported at least 1 local symptom at the vaccination site, and 61.8% had axillary lymphadenopathy, 15.0% developed satellite lesions, and 7.6% developed a rash away from the vaccination site. Fever developed in 21.5%. No differences were noted in local or systemic reactions between the 3 dilution groups (P>.05 for each comparison). A total of 25% of volunteers missed scheduled duties due to vaccine-related symptoms.


CONCLUSIONS
Even at diluted doses, APSV is an effective smallpox vaccine, allowing for expansion of the current stockpile. However, reactogenicity was not reduced with dilution of the vaccine and, as with other smallpox vaccines, may impair daily activities.
Talbot
Thomas R
TR
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.S
Stapleton
Jack T
JT
Brady
Rebecca C
RC
Winokur
Patricia L
PL
Bernstein
David I
DI
Germanson
Teresa
T
Yoder
Sandra M
SM
Rock
Michael T
MT
Crowe
James E
JE
Edwards
Kathryn M
KM
D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D012900:Smallpox Vaccine / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000600:supply & distribution; D014611:Vaccination; D012901:Variola virus / Q000276:immunology
D000914:Antibodies, Viral; D012900:Smallpox Vaccine