title: 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.
abstract: 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.
authors.affiliation: Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD, United States. robert.a.kuschner.mil@mail.mil
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kuschner
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Russell
authors.forename: Mary
authors.initials: M
authors.lastname: Abuja
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Bauer
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Faix
authors.forename: Howard
authors.initials: H
authors.lastname: Hait
authors.forename: Jennifer
authors.initials: J
authors.lastname: Henrick
authors.forename: Michael
authors.initials: M
authors.lastname: Jacobs
authors.forename: Alan
authors.initials: A
authors.lastname: Liss
authors.forename: Julia A
authors.initials: JA
authors.lastname: Lynch
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Arthur G
authors.initials: AG
authors.lastname: Lyons
authors.forename: Mohammad
authors.initials: M
authors.lastname: Malik
authors.forename: James E
authors.initials: JE
authors.lastname: Moon
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Stubbs
authors.forename: Wellington
authors.initials: W
authors.lastname: Sun
authors.forename: Doug
authors.initials: D
authors.lastname: Tang
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Towle
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Walsh
authors.forename: Deborah
authors.initials: D
authors.lastname: Wilkerson
mesh_terms: D000208:Acute Disease; D000258:Adenovirus Infections, Human / Q000276:immunology / Q000517:prevention & control*; D062705:Adenovirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D000260:Adenoviruses, Human / Q000276:immunology*; D000284:Administration, Oral; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008889:Military Personnel; D012141:Respiratory Tract Infections / Q000276:immunology / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D062705:Adenovirus Vaccines