UMMS Affiliation

Center for Infectious Disease and Vaccine Research; Department of Medicine, Division of Infectious Diseases and Immunology

Publication Date


Document Type



Immunity | Immunology and Infectious Disease | Immunology of Infectious Disease | Immunoprophylaxis and Therapy | Infectious Disease


BACKGROUND: We conducted a double-blind, randomized trial of three dilutions of vaccinia virus vaccine in previously unimmunized adults in order to assess the clinical success rates, humoral responses, and virus-specific activity of cytotoxic T cells and interferon-gamma-producing T cells.

METHODS: Sixty healthy adults were inoculated intradermally by bifurcated needle with undiluted vaccine (dose, 10(7.8) plaque-forming units [pfu] per milliliter), a 1:10 dilution (dose, 10(6.5) pfu per milliliter), or a 1:100 dilution (dose, 10(5.0) pfu per milliliter); there were 20 subjects in each group. The subjects were monitored with respect to vesicle formation (an indicator of successful vaccination), the viral titer at the time of peak lesion formation, antiviral antibodies, and cellular immune responses.

RESULTS: A vaccinia vesicle developed in 19 of the 20 subjects who received undiluted vaccine (95 percent), 14 of the 20 who received the 1:10 dilution (70 percent), and 3 of the 20 who received the 1:100 dilution (15 percent). One month after vaccination, 34 of 36 subjects with vesicles had antibody responses, as compared with only 1 of 24 subjects without clinical evidence of vaccinia virus replication. Vigorous cytotoxic T-cell and interferon-gamma responses occurred in 94 percent of subjects with vesicles, and a cytotoxic T-cell response occurred in only one subject without a vesicle.

CONCLUSIONS: The vaccinia virus vaccine (which was produced in 1982 or earlier) still has substantial potency when administered by a bifurcated needle to previously unvaccinated adults. Diluting the vaccine reduces the rate of successful vaccination. The development of vesicular skin lesions after vaccination correlates with the induction of the antibody and T-cell responses that are considered essential for clearing vaccinia virus infections.


smallpox vaccine, vaccinia virus vaccine

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Copyright © 2002 Massachusetts Medical Society. Publisher PDF posted after 6 months as allowed by the publisher's author rights policy at

DOI of Published Version



N Engl J Med. 2002 Apr 25;346(17):1275-80. Epub 2002 Mar 28. doi:10.1056/NEJMoa013431 Link to article on publisher's site

Journal/Book/Conference Title

The New England journal of medicine

Related Resources

Link to Article in PubMed

PubMed ID