Sharon E. Frey, M.D., Frances K. Newman, M.S., John Cruz, B.S., W. Brian Shelton, Ph.D., Janice M. Tennant, M.P.H., Tamara Polach, B.S., Alan L. Rothman, M.D., Jeffrey S. Kennedy, M.D., Mark Wolff, Ph.D., Robert B. Belshe, M.D., and Francis A. Ennis, M.D.
Background We conducted a double-blind, randomized trial ofthree dilutions of vaccinia virus vaccine in previously unimmunizedadults in order to assess the clinical success rates, humoralresponses, and virus-specific activity of cytotoxic T cellsand interferon-producing T cells.
Methods Sixty healthy adults were inoculated intradermally bybifurcated needle with undiluted vaccine (dose, 107.8 plaque-formingunits [pfu] per milliliter), a 1:10 dilution (dose, 106.5 pfuper milliliter), or a 1:100 dilution (dose, 105.0 pfu per milliliter);there were 20 subjects in each group. The subjects were monitoredwith respect to vesicle formation (an indicator of successfulvaccination), 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 subjectswho received undiluted vaccine (95 percent), 14 of the 20 whoreceived the 1:10 dilution (70 percent), and 3 of the 20 whoreceived the 1:100 dilution (15 percent). One month after vaccination,34 of 36 subjects with vesicles had antibody responses, as comparedwith only 1 of 24 subjects without clinical evidence of vacciniavirus replication. Vigorous cytotoxic T-cell and interferon-responses occurred in 94 percent of subjects with vesicles,and a cytotoxic T-cell response occurred in only one subjectwithout a vesicle.
Conclusions The vaccinia virus vaccine (which was produced in1982 or earlier) still has substantial potency when administeredby a bifurcated needle to previously unvaccinated adults. Dilutingthe vaccine reduces the rate of successful vaccination. Thedevelopment of vesicular skin lesions after vaccination correlateswith the induction of the antibody and T-cell responses thatare considered essential for clearing vaccinia virus infections.
Source Information
From the Department of Medicine, National Institute of Allergy and Infectious Diseases Vaccine and Treatment Evaluation Unit, Saint Louis University School of Medicine, St. Louis (S.E.F., F.K.N., W.B.S., J.M.T., T.P., R.B.B.); the Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester (J.C., A.L.R., J.S.K., F.A.E); and the Emmes Corporation, Rockville, Md. (M.W.). This article was published at www.nejm.org on March 28, 2002.
Address reprint requests to Dr. Frey at the Division of Infectious Diseases and Immunology, Saint Louis University Health Sciences Center, 3635 Vista Ave. (FDT-8N), St. Louis, MO 63110.
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