Response to smallpox vaccine in persons immunized in the distant past

JAMA. 2003 Jun 25;289(24):3295-9. doi: 10.1001/jama.289.24.3295.

Abstract

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 =.002).

Conclusions: Previously vaccinated persons can be successfully revaccinated with diluted (<or=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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antibodies, Viral / blood
  • Humans
  • Immunization, Secondary* / adverse effects
  • Immunologic Memory*
  • Middle Aged
  • Single-Blind Method
  • Skin Diseases, Papulosquamous / etiology*
  • Skin Diseases, Papulosquamous / immunology
  • Skin Diseases, Papulosquamous / virology
  • Smallpox Vaccine / administration & dosage*
  • Smallpox Vaccine / adverse effects
  • Smallpox Vaccine / immunology
  • Vaccination* / adverse effects
  • Vaccinia virus / isolation & purification
  • Virus Shedding

Substances

  • Antibodies, Viral
  • Smallpox Vaccine