A Single-Cycle Adenovirus Type 7 Vaccine for Prevention of Acute Respiratory Disease

Abstract

Adenovirus type 7 (Ad7) infection is associated with acute respiratory disease (ARD), especially in military recruits living in close quarters. Recently, several outbreaks of Ad7 infections have occurred in civilian populations, with some cases leading to death. However, the current Ad7 vaccine is licensed for use only in military recruits because it utilizes an orally delivered wild type virus which is shed in the stool for 28 days after immunization. This poses a safety risk due to the possibility of virus spread to vulnerable populations. To address the need for a safer Ad7 vaccine for use in civilian populations, we developed a single-cycle Ad7 virus (scAd7). This scAd7 virus is deleted for the Ad7 fiber protein, so that viruses produced outside of complementing cells lines lack this essential structural protein and have severely reduced infectivity. In vitro studies in noncomplementing A549 cells showed that the scAd7 virus has genomic DNA replication kinetics and Ad7 hexon expression similar to a replication-competent virus; however, virus progeny produced after infection has impaired infectivity. Therefore, this scAd7 virus combines the safety advantages of a replication-defective virus with the increased Ad7 gene expression of a replication-competent virus. Due to these advantages, we believe that scAd7 viruses should be further studied as an alternative, safer Adenovirus 7 vaccine.