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

• DOI: 10.1016/j.vaccine.2013.04.035
• Publication Date: 2013-04-25T19:00:29Z
• Authors: Robert A. Kuschner; Kevin L. Russell; Mary Abuja; Kristen M. Bauer; Dennis J. Faix; Howard Hait; Jennifer Henrick; Michael Jacobs; Alan Liss; Julia A. Lynch; Qi Liu; Arthur G. Lyons; Mohammad Malik; James E. Moon; Jeremiah Stubbs; Wellington Sun; Doug Tang; Andrew C. Towle; Douglas S. Walsh; Deborah Wilkerson
• Keywords: Adult; Male; 0301 basic medicine; Adenoviruses, Human; Administration, Oral; 3. Good health; Adenovirus Infections, Human; Young Adult; 03 medical and health sciences; Military Personnel; Double-Blind Method; Adenovirus Vaccines; Acute Disease; Humans; Female; Respiratory Tract Infections

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 4.5 log10 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.