Vaccine 31 (2013) 2963–2971 Contents lists available at SciVerse ScienceDirect Vaccine journal homepage: www.elsevier.com/locate/vaccine 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 Robert A. Kuschner a,∗ , Kevin L. Russell b , Mary Abuja b , Kristen M. Bauer a , Dennis J. Faix b , Howard Hait c , Jennifer Henrick c , Michael Jacobs d , Alan Liss c , Julia A. Lynch a , Qi Liu e , Arthur G. Lyons a , Mohammad Malik d , James E. Moon a , Jeremiah Stubbs a , Wellington Sun a , Doug Tang a , Andrew C. Towle f , Douglas S. Walsh a , Deborah Wilkerson c , the Adenovirus Vaccine Efficacy Trial Consortium 1 a Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD, United States b Naval Health Research Center, 140 Sylvester Avenue, San Diego, CA, United States c Barr Laboratories Inc., 2 Quaker Road, Pomona, NY, United States d Captain James A Lovell Federal Health Care Center, 3001 Green Bay Road, North Chicago, IL, United States e Barr Laboratories, 8 Delaney Drive, Newtown, PA, United States f VaccGen International LLC, 8 Cambridge Court, Larchmont, NY, United States article info Article history: Received 25 May 2012 Received in revised form 2 February 2013 Accepted 11 April 2013 Available online 25 April 2013 Keywords: Adenovirus Type 4 and Type 7 vaccine, live, oral Adenovirus Type 4 ADV-4 Adenovirus Type 7 ADV-7 Oral vaccine Live vaccines Acute respiratory infection 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 log 10 TCID 50 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. Published by Elsevier Ltd. ∗ Corresponding author. E-mail addresses: robert.a.kuschner.mil@mail.mil (R.A. Kuschner), Kevin.russell4@us.army.mil (K.L. Russell), mary.abuja@med.navy.mil (M. Abuja), Kristen.Bauer@afrims.org (K.M. Bauer), dennis.faix@med.navy.mil (D.J. Faix), howardhait@edenridgeassociates.com (H. Hait), jennifer.henrick@tevapharm.com (J. Henrick), michael.jacobs@med.navy.mil (M. Jacobs), alan.liss@fda.hhs.gov (A. Liss), Julia.lynch@us.army.mil (J.A. Lynch), Qi.liu@msn.com (Q. Liu), Arthur.lyons@us.army.mil (A.G. Lyons), Mohammad.malik@va.gov (M. Malik), james.e.moon@us.army.mil (J.E. Moon), jeremiah.stubbs@us.army.mil (J. Stubbs), wellington.sun@fda.hhs.gov (W. Sun), dtang38@verizon.net (D. Tang), andy t1@msn.com (A.C. Towle), douglas.walsh@afrims.org (D.S. Walsh), debbie.s.wilkerson@medtronic.com (D. Wilkerson). 1 See Appendix A. 1. Introduction Military recruits at basic training (BT) camps are particularly susceptible to respiratory infections due to the nature of their training, in which large numbers of individuals from different geo- graphic locations live and train together in relatively confined spaces for extended periods. Despite the effectiveness of influenza vaccination, initiated during World War II, recurrent epidemics of acute respiratory disease (ARD) remain a significant problem in new recruits undergoing basic training (BT). Typical ARD in recruits is a febrile illness with cough, sore throat, nasal discharge, headache and fatigue that persists for 3 to 10 days. The illness is debilitating, a major cause of lost training time, complicated by pneumonia in about 10% of cases and can, although rarely, be fatal. Studies have 0264-410X/$ – see front matter. Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.vaccine.2013.04.035