Context There is renewed interest in use of smallpox vaccine due to the potential
for a bioterrorist attack. This would involve vaccinating health care workers
who were previously vaccinated.
Objective To evaluate the use of diluted vaccinia virus in vaccination of previously
vaccinated (non-naive) participants.
Design, Setting, and Participants Eighty non-naive participants, aged 32 to 60 years, were randomized
in a single-blinded study to receive either undiluted or diluted (1:3.2, 1:10,
or 1:32) doses of smallpox vaccine. A comparison group, aged 18 to 31 years,
of 10 vaccinia-naive participants received undiluted vaccine. Participants
were enrolled between April 1 and May 15, 2002, at the National Institute
of Allergy and Infectious Diseases Vaccine and Treatment Evaluation Unit at
Saint Louis University, St Louis, Mo.
Intervention Smallpox vaccine was administered by scarification using 15 skin punctures
in the deltoid region of the arm.
Main Outcome Measures Presence of a major reaction, defined as a vesicular or pustular lesion
or area of palpable induration surrounding a central lesion following vaccination,
and measures of viral shedding and antibody titers.
Results Initial vaccination resulted in a major reaction in 64 of 80 non-naive
participants. Ninety-five percent of non-naive participants had major reactions
in the undiluted group, 90% in the 1:3.2 dilution group, 81% in the 1:10 dilution
group, and 52.6% in the 1:32 dilution group. All (n = 10) of the vaccinia-naive
participants had major reactions. Compared with vaccinia-naive participants,
non-naive participants had significantly smaller skin lesions (P = .04) and significantly less incidence of fever (P = .02). Preexisting antibody was present in 76 of 80 non-naive participants.
Antibody responses were significantly higher and occurred more rapidly in
the non-naive participants compared with the vaccinia-naive participants (P = .002 for day 28 and P = .003
for 6 months). Vaccinia-naive participants shed virus from the vaccination
site 2 to 6 days longer and had significantly higher peak mean viral titers
when compared with the non-naive participants (P =
Conclusions Previously vaccinated persons can be successfully revaccinated with
diluted (≤1:10) smallpox vaccine. Fewer adverse reactions were observed
in this study of non-naive participants when compared with events in vaccinia-naive
participants, which may be due to immunologic memory.