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

doi:10.3390/vaccines11071144

Vaccines (Jun 2023)

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

DOI: https://doi.org/10.3390/vaccines11071144
Journal volume & issue: Vol. 11, no. 7
p. 1144

Abstract

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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.

Published in Vaccines

ISSN: 2076-393X (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine
Website: http://www.mdpi.com/journal/vaccines

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