Dose-Dependent Neutralizing-Antibody Responses to Vaccinia

To evaluate the humoral immune responses to smallpoxvaccine stocks currently available in the United States (Dryvax; Wyeth) and to generate data for comparison of responses to newly produced lots of smallpox vaccine, we evaluated dose-response effects, using undiluted and diluted smallpox vaccine. At 28 and 56 days after vaccination, serum samples were obtained from vaccinated subjects ( ) who had N p 674 participated in a randomized, single-blinded trial of an undiluted or a 1:5 or 1:10 dilution of smallpox vaccine and who subsequently were tested for plaque-reduction neutralizing-antibody titer. All subjects who developed a vesicle after vaccination also developed neutralizing antibodies by day 28. Subjects given either a 1:5 or 1:10 dilution of vaccinia had significantly higher neutralizing-antibody titers than did subjects given undiluted vaccine. Larger lesion size and fever after vaccination were associated with significantly higher neutralizing-antibody titers after vaccination. Understanding the immune responses to vaccinia and other smallpox vaccines will be important in the development of strategies to vaccinate large numbers of persons by use of new formulations of vaccines and to develop less reactogenic smallpox vaccines. We recently completed 2 dose-response studies of vaccinia (Dryvax; Wyeth) in persons 18–32 years of age who had never previously been vaccinated [1, 2]. In a pilot study, we evaluated vaccinia concentrations of 10 7.8 ,1 0 6.5 , and 10 5.0 pfu/mL, given by bifurcated needle (measured vaccinia dose of 10 5.0 –10 1.9 on a needle), for vaccinia infection as indicated by