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A phase 3, randomized, double-blind, placebo-controlled study of the safety and efficacy of the live, oral adenovirus type 4 and type 7 vaccine, in U.S. military recruits

Kuschner, Robert A., Russell, Kevin L., Abuja, Mary, Bauer, Kristen M., Faix, Dennis J., Hait, Howard, Henrick, Jennifer, Jacobs, Michael, Liss, Alan, Lynch, Julia A., Liu, Qi, Lyons, Arthur G., Malik, Mohammad, Moon, James E., Stubbs, Jeremiah, Sun, Wellington, Tang, Doug, Towle, Andrew C., Walsh, Douglas S., Wilkerson, Deborah
Vaccine 2013 v.31 no.28 pp. 2963-2971
adults, antibodies, blood serum, deglutition, neutralization, respiratory tract diseases, seroconversion, vaccines, volunteers, United States
Adenovirus (ADV) types 4 (ADV-4) and 7 (ADV-7) are presently the major cause of febrile acute respiratory disease (ARD) in U.S. military recruits. We conducted a multi-center, randomized, double-blind, placebo-controlled phase 3 study of the new vaccine to assess its safety and efficacy. Healthy adults at two basic training sites were randomly assigned to receive either vaccine (two enteric-coated tablets consisting of no less than 4.5log10 TCID50 of live ADV-4 or ADV-7) or placebo in a 3:1 ratio. Volunteers were observed throughout the approximate eight weeks of their basic training and also returned for four scheduled visits. The primary endpoints were prevention of febrile ARD due to ADV-4 and seroconversion of neutralizing serum antibodies to ADV-7, which was not expected to circulate in the study population during the course of the trial. A total of 4151 volunteers were enrolled and 4040 (97%) were randomized and included in the primary analysis (110 were removed prior to randomization and one was removed after randomization due to inability to swallow tablets). A total of 49 ADV-4 febrile ARD cases were identified with 48 in the placebo group and 1 in the vaccine group (attack rates of 4.76% and 0.03%, respectively). Vaccine efficacy was 99.3% (95% CI, 96.0–99.9; P<0.001). Seroconversion rates for vaccine recipients for ADV-4 and ADV-7 were 94.5% (95% CI, 93.4–95.5%) and 93.8% (95% CI: 93.4–95.2%), respectively. The vaccine was well tolerated as compared to placebo. We conclude that the new live, oral ADV-4 and ADV-7 vaccine is safe and effective for use in groups represented by the study population.