Publication Database

Generation of "OP7 chimera" defective interfering influenza A particle preparations free of infectious virus that show antiviral efficacy in mice (2023)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Dogra, Tanya

Pelz, Lars

Boehme, Julia D.

Kuechler, Jan

Kershaw, Olivia (WE 12)

Marichal-Gallardo, Pavel

Baelkner, Maike

Hein, Marc D.

Gruber, Achim D. (WE 12)

Benndorf, Dirk

Genzel, Yvonne

Bruder, Dunja

Kupke, Sascha Y.

Reichl, Udo

Quelle

Scientific reports

Bandzählung: 13

Heftzählung: 1

Seiten: Artikelnummer: 20936

ISSN: 2045-2322

Sprache

Englisch

Verweise

URL (Volltext): https://pubmed.ncbi.nlm.nih.gov/38017026/

DOI: 10.1038/s41598-023-47547-1

Pubmed: 38017026

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.