Differential Genome Replication of a Unique Single-Amino-Acid Mutation in the Adenovirus-4 Component of the Live Oral Adenovirus Type 4 and Type 7 Vaccine
Natalie D. Collins,
Shannon Beaty,
Elana Wallace,
Yuanzhang Li,
Mark Sanborn,
Yu Yang,
Anima Adhikari,
Paul Shabram,
Kelly Warfield,
Nicos Karasavvas,
Robert A. Kuschner,
Jun Hang
Affiliations
Natalie D. Collins
Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Shannon Beaty
Emergent BioSolutions, Inc., Gaithersburg, MD 20879, USA
Elana Wallace
Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Yuanzhang Li
Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Mark Sanborn
Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Yu Yang
Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Anima Adhikari
Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Paul Shabram
Emergent BioSolutions, Inc., Gaithersburg, MD 20879, USA
Kelly Warfield
Emergent BioSolutions, Inc., Gaithersburg, MD 20879, USA
Nicos Karasavvas
Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Robert A. Kuschner
Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Jun Hang
Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
The FDA-approved Adenovirus Type 4 and Type 7 Vaccine, Live, Oral is highly effective and essential in preventing acute respiratory diseases (ARDs) in U.S. military recruits. Our study revealed the presence of a previously undetected mutation, not found in the wild-type human adenovirus type 4 (HAdV-4) component of the licensed vaccine, which contains an amino acid substitution (P388T) in the pre-terminal protein (pTP). This study demonstrated that replication of the T388 HAdV-4 vaccine mutant virus is favored over the wild type in WI-38 cells, the cell type utilized in vaccine manufacturing. However, results from serial human stool specimens of vaccine recipients support differential genome replication in the gastrointestinal tract (GI), demonstrated by the steady decline of the percentage of mutant T388 vaccine virus. Since vaccine efficacy depends upon GI replication and the subsequent immune response, the mutation can potentially impact vaccine efficacy.
