Generation of “OP7 chimera” defective interfering influenza A particle preparations free of infectious virus that show antiviral efficacy in mice
Abstract Influenza A virus (IAV) defective interfering particles (DIPs) are considered as new promising antiviral agents. Conventional DIPs (cDIPs) contain a deletion in the genome and can only replicate upon co-infection with infectious standard virus (STV), during which they suppress STV replicati...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-47547-1 |
| _version_ | 1797415225251594240 |
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| author | Tanya Dogra Lars Pelz Julia D. Boehme Jan Kuechler Olivia Kershaw Pavel Marichal-Gallardo Maike Baelkner Marc D. Hein Achim D. Gruber Dirk Benndorf Yvonne Genzel Dunja Bruder Sascha Y. Kupke Udo Reichl |
| author_facet | Tanya Dogra Lars Pelz Julia D. Boehme Jan Kuechler Olivia Kershaw Pavel Marichal-Gallardo Maike Baelkner Marc D. Hein Achim D. Gruber Dirk Benndorf Yvonne Genzel Dunja Bruder Sascha Y. Kupke Udo Reichl |
| author_sort | Tanya Dogra |
| collection | DOAJ |
| description | Abstract Influenza A virus (IAV) defective interfering particles (DIPs) are considered as new promising antiviral agents. Conventional DIPs (cDIPs) contain a deletion in the genome and can only replicate upon co-infection with infectious standard virus (STV), during which they suppress STV replication. We previously discovered a new type of IAV DIP “OP7” that entails genomic point mutations and displays higher antiviral efficacy than cDIPs. To avoid safety concerns for the medical use of OP7 preparations, we developed a production system that does not depend on infectious IAV. We reconstituted a mixture of DIPs consisting of cDIPs and OP7 chimera DIPs, in which both harbor a deletion in their genome. To complement the defect, the deleted viral protein is expressed by the suspension cell line used for production in shake flasks. Here, DIP preparations harvested are not contaminated with infectious virions, and the fraction of OP7 chimera DIPs depended on the multiplicity of infection. Intranasal administration of OP7 chimera DIP material was well tolerated in mice. A rescue from an otherwise lethal IAV infection and no signs of disease upon OP7 chimera DIP co-infection demonstrated the remarkable antiviral efficacy. The clinical development of this new class of broad-spectrum antiviral may contribute to pandemic preparedness. |
| first_indexed | 2024-03-09T05:44:46Z |
| format | Article |
| id | doaj.art-14074a084c1e479b80e20d113a9f8b14 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T05:44:46Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-14074a084c1e479b80e20d113a9f8b142023-12-03T12:21:34ZengNature PortfolioScientific Reports2045-23222023-11-0113111310.1038/s41598-023-47547-1Generation of “OP7 chimera” defective interfering influenza A particle preparations free of infectious virus that show antiviral efficacy in miceTanya Dogra0Lars Pelz1Julia D. Boehme2Jan Kuechler3Olivia Kershaw4Pavel Marichal-Gallardo5Maike Baelkner6Marc D. Hein7Achim D. Gruber8Dirk Benndorf9Yvonne Genzel10Dunja Bruder11Sascha Y. Kupke12Udo Reichl13Max Planck Institute for Dynamics of Complex Technical Systems, Bioprocess EngineeringMax Planck Institute for Dynamics of Complex Technical Systems, Bioprocess EngineeringInstitute of Medical Microbiology, Infection Prevention and Control, Infection Immunology Group, Health Campus Immunology, Infectiology and Inflammation, Otto Von Guericke University MagdeburgMax Planck Institute for Dynamics of Complex Technical Systems, Bioprocess EngineeringDepartment of Veterinary Pathology, Freie Universität BerlinMax Planck Institute for Dynamics of Complex Technical Systems, Bioprocess EngineeringInstitute of Medical Microbiology, Infection Prevention and Control, Infection Immunology Group, Health Campus Immunology, Infectiology and Inflammation, Otto Von Guericke University MagdeburgBioprocess Engineering, Otto Von Guericke University MagdeburgDepartment of Veterinary Pathology, Freie Universität BerlinMax Planck Institute for Dynamics of Complex Technical Systems, Bioprocess EngineeringMax Planck Institute for Dynamics of Complex Technical Systems, Bioprocess EngineeringInstitute of Medical Microbiology, Infection Prevention and Control, Infection Immunology Group, Health Campus Immunology, Infectiology and Inflammation, Otto Von Guericke University MagdeburgMax Planck Institute for Dynamics of Complex Technical Systems, Bioprocess EngineeringMax Planck Institute for Dynamics of Complex Technical Systems, Bioprocess EngineeringAbstract Influenza A virus (IAV) defective interfering particles (DIPs) are considered as new promising antiviral agents. Conventional DIPs (cDIPs) contain a deletion in the genome and can only replicate upon co-infection with infectious standard virus (STV), during which they suppress STV replication. We previously discovered a new type of IAV DIP “OP7” that entails genomic point mutations and displays higher antiviral efficacy than cDIPs. To avoid safety concerns for the medical use of OP7 preparations, we developed a production system that does not depend on infectious IAV. We reconstituted a mixture of DIPs consisting of cDIPs and OP7 chimera DIPs, in which both harbor a deletion in their genome. To complement the defect, the deleted viral protein is expressed by the suspension cell line used for production in shake flasks. Here, DIP preparations harvested are not contaminated with infectious virions, and the fraction of OP7 chimera DIPs depended on the multiplicity of infection. Intranasal administration of OP7 chimera DIP material was well tolerated in mice. A rescue from an otherwise lethal IAV infection and no signs of disease upon OP7 chimera DIP co-infection demonstrated the remarkable antiviral efficacy. The clinical development of this new class of broad-spectrum antiviral may contribute to pandemic preparedness.https://doi.org/10.1038/s41598-023-47547-1 |
| spellingShingle | Tanya Dogra Lars Pelz Julia D. Boehme Jan Kuechler Olivia Kershaw Pavel Marichal-Gallardo Maike Baelkner Marc D. Hein Achim D. Gruber Dirk Benndorf Yvonne Genzel Dunja Bruder Sascha Y. Kupke Udo Reichl Generation of “OP7 chimera” defective interfering influenza A particle preparations free of infectious virus that show antiviral efficacy in mice Scientific Reports |
| title | Generation of “OP7 chimera” defective interfering influenza A particle preparations free of infectious virus that show antiviral efficacy in mice |
| title_full | Generation of “OP7 chimera” defective interfering influenza A particle preparations free of infectious virus that show antiviral efficacy in mice |
| title_fullStr | Generation of “OP7 chimera” defective interfering influenza A particle preparations free of infectious virus that show antiviral efficacy in mice |
| title_full_unstemmed | Generation of “OP7 chimera” defective interfering influenza A particle preparations free of infectious virus that show antiviral efficacy in mice |
| title_short | Generation of “OP7 chimera” defective interfering influenza A particle preparations free of infectious virus that show antiviral efficacy in mice |
| title_sort | generation of op7 chimera defective interfering influenza a particle preparations free of infectious virus that show antiviral efficacy in mice |
| url | https://doi.org/10.1038/s41598-023-47547-1 |
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