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
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...
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| Format: | Article |
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MDPI AG
2023-06-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/11/7/1144 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Natalie D. Collins |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T00:35:02Z |
| format | Article |
| id | doaj.art-3b23e21ed396436baeff6b217e105982 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-11T00:35:02Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-3b23e21ed396436baeff6b217e1059822023-11-18T21:40:15ZengMDPI AGVaccines2076-393X2023-06-01117114410.3390/vaccines11071144Differential Genome Replication of a Unique Single-Amino-Acid Mutation in the Adenovirus-4 Component of the Live Oral Adenovirus Type 4 and Type 7 VaccineNatalie D. Collins0Shannon Beaty1Elana Wallace2Yuanzhang Li3Mark Sanborn4Yu Yang5Anima Adhikari6Paul Shabram7Kelly Warfield8Nicos Karasavvas9Robert A. Kuschner10Jun Hang11Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAEmergent BioSolutions, Inc., Gaithersburg, MD 20879, USAWalter Reed Army Institute of Research, Silver Spring, MD 20910, USAWalter Reed Army Institute of Research, Silver Spring, MD 20910, USAWalter Reed Army Institute of Research, Silver Spring, MD 20910, USAWalter Reed Army Institute of Research, Silver Spring, MD 20910, USAWalter Reed Army Institute of Research, Silver Spring, MD 20910, USAEmergent BioSolutions, Inc., Gaithersburg, MD 20879, USAEmergent BioSolutions, Inc., Gaithersburg, MD 20879, USAWalter Reed Army Institute of Research, Silver Spring, MD 20910, USAWalter Reed Army Institute of Research, Silver Spring, MD 20910, USAWalter Reed Army Institute of Research, Silver Spring, MD 20910, USAThe 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.https://www.mdpi.com/2076-393X/11/7/1144adenovirusHAdV-4DNA virusvaccinereplicationmutation |
| spellingShingle | 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 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 Vaccines adenovirus HAdV-4 DNA virus vaccine replication mutation |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | adenovirus HAdV-4 DNA virus vaccine replication mutation |
| url | https://www.mdpi.com/2076-393X/11/7/1144 |
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