Emergence of Adenovirus Type 14 in US Military Recruits—A New Challenge

Abstract

In this issue of the Journal, Metzgar et al. [1] report a significant addition to the adenovirus (Ad) types infecting US military recruits with acute respiratory disease (ARD). Their ongoing epidemiological studies, which use rapid molecular diagnostic procedures, enabled the detection and identification of a species B2 Ad, type 14 (Ad14), that had not been previously observed in US military recruits. This virus was originally recovered 50 years ago from Dutch recruits [2], with only 2 subsequent reports of ARD associated with Ad14 [1, 3]. In contrast to the B1 Ads (i.e., types 3, 7, and 21) that often infect the respiratory tract, Ad14 respiratory infections have been very rarely observed in adult military and civilian populations [4]. At present, studies are under way at military training centers to field test replacements for the live oral Ad4 and Ad7 vaccines that had been used for 25 years but were lost when production ceased in the 1990s [5–7]. The recent recovery of Ad14 raises new questions as to whether Ad14 will take hold as a respiratory disease agent in civilian and military populations and whether the candidate Ad4 and Ad7 vaccines will protect against Ad14. The absence of identified Ad14 respiratory infections in the United States suggests that we have highly susceptible civilian and military populations. Review of past experience with the live oral Ad vaccines may be of value in assessing the long-term threat of Ad14 to recruits. Previous observation of responses to the Ad4 and Ad7 vaccines indicated that they were highly effective against homologous viruses and Ad3 [6, 7]. Vaccines responses to Ad3 were attributed to some level of Ad3 occurring naturally and to Ad3 being antigenically related to Ad7, both being species B1 viruses. Therefore, after exposure to the Ad7 vaccine virus, heterotypic responses to Ad3 occurred [8]. In contrast to Ad3, naturally occurring background infections with Ad21, also a species B1 virus, have been considered rare. Recent studies of recruits with ARD found only small numbers infected with Ad21 [1]. Only a few additional Ad21 infections were identified via antibody testing, suggesting that the virus currently is not highly communicable [9, 10]. However, in 1975–1976, Ad21 was recovered from large numbers of recruits with ARD who had been vaccinated against Ad4 and Ad7. ARD-associated Ad21 infections continued for months at most training facilities, resulting in the testing of an experimental live oral vaccine [11, 12]. However, long-term observation revealed that Ad21 did not persist as a significant cause of ARD, even though outbreaks occurred in the 1970s and again in 1985 [13]. Thus, there has been no interest in renewing studies of an Ad21 vaccine. It is possible that Ad14 and other Ads could cause significant ARD morbidity among military recruits for a limited period and then disappear as an important cause of respiratory disease. It is also possible that some protection against emerging Ads could be provided as a result of heterotypic antibody responses to other viruses, including the Ad7 vaccine virus. Past studies in The Netherlands found that Ad14-associated ARD did not persist in their recruits [2, 14]. Additionally, the development of heterotypic antibody to Ad14 after Ad7 immunization was reported in 1960 [15]. Contemporary serologic surveys of new US military recruits will provide important information on their susceptibility. Testing archival serum-bank specimens from recruits vaccinated against Ad4 and Ad7 and from recruits with ARD who had laboratory confirmation of a specific Ad type could provide data on the occurrence of heterotypic antibody reReceived 4 June 2007; accepted 4 June 2007; electronically published 31 October 2007. Potential conflicts of interest: none reported. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the true views of the Department of the Army or the Department of Defense. Reprints or correspondence: Dr. Leonard N. Binn, Div. of Viral Diseases, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD 20910 (leonard.binn@na.amedd.army.mil). The Journal of Infectious Diseases 2007; 196:1436 –7 This article is in the public domain, and no copyright is claimed. 0022-1899/2007/19610-0003$15.00 DOI: 10.1086/522969 E D I T O R I A L C O M M E N T A R Y