---
title: "Fed-batch production of antiviral OP7 chimera defective interfering influenza A particles"
id: "biorxiv-0-fed-batch-production-of-antiviral-op7-chimera-defective-interfering-influenza-a"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-0-fed-batch-production-of-antiviral-op7-chimera-defective-interfering-influenza-a"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.30.755589v1?rss=1"
published_at: "2026-10-01T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Fed-batch production of antiviral OP7 chimera defective interfering influenza A particles
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-0-fed-batch-production-of-antiviral-op7-chimera-defective-interfering-influenza-a
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.30.755589v1?rss=1)
- **Published At:** 2026-10-01T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study reports establishment of a **fed-batch** cell culture process to produce the antiviral **OP7 chimera defective interfering particles (DIPs)** for Influenza A virus (IAV), aiming to combine high yield with simpler implementation than perfusion. - A feeding regimen overcame the typical cell density effect, enabling productive infection in stirred-tank reactors up to 10E+6 cells/mL. - The fed-batch process yielded a peak virus titer of **3.8 log10(HAU/100 µL)**, representing a **3.4-fold increase** versus a reference batch production. - Material produced in fed-batch showed significantly increased **interfering bioactivity** in an in vitro potency assay compared with the reference batch. - Despite achieving approximately twofold lower virus titers than material previously produced in perfusion mode, the fed-batch product’s antiviral potency matched that of the perfusion-produced OP7 chimera DIP. - The authors demonstrate robustness of OP7 chimera DIP seed virus trains and report availability of GMP MDCK-PB2(sus) cell and OP7 chimera virus banks for future biomanufacturing. - The fed-batch process is presented as a practical additional option for pharmaceutical-grade OP7 chimera DIP manufacturing under GMP for clinical testing and scale-up. - Competing interests: patents for OP7 use as an antiviral for IAV are approved in the USA and pending in EU and Japan (patent holders S.Y.K. and U.R.); a patent for OP7 use against coronavirus is pending (holders S.Y.K. and U.R.). - Funder: Max Planck Innovation, MTTADYSY006. The article is a preprint and has not been peer reviewed.
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Wiebke Holste 1 Fraunhofer Institute for Toxicology and Experimental Medicine, Pharmaceutical Biotechnology, Braunschweig, Germany; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Wiebke%2BHolste%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Holste%20W&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AWiebke%2BHolste%2B) Sascha Young Kupke 2 Max Planck Institute for Dynamics of Complex Technical Systems, Bioprocess Engineering, Magdeburg, Germany; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Sascha%2BYoung%2BKupke%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Kupke%20SY&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ASascha%2BYoung%2BKupke%2B) * [ORCID record for Sascha Young Kupke](http://orcid.org/0000-0003-3943-9718 "Open in new tab") * For correspondence: kupke@mpi-magdeburg.mpg.de Claudius Seitz 1 Fraunhofer Institute for Toxicology and Experimental Medicine, Pharmaceutical Biotechnology, Braunschweig, Germany; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Claudius%2BSeitz%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Seitz%20C&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AClaudius%2BSeitz%2B) Udo Reichl 3 Max Planck Institute for Dynamics of Complex Technical Systems, Bioprocess Engineering, Magdeburg, Germany and Otto von Guericke University, Bioprocess Engineering, Magdeburg, Germany * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Udo%2BReichl%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Reichl%20U&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AUdo%2BReichl%2B) Holger Ziehr 1 Fraunhofer Institute for Toxicology and Experimental Medicine, Pharmaceutical Biotechnology, Braunschweig, Germany; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Holger%2BZiehr%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Ziehr%20H&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AHolger%2BZiehr%2B) * [Abstract](https://www.biorxiv.org/content/10.64898/2026.09.30.755589v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5833600/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.09.30.755589v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5833600/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.09.30.755589v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5833600/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.09.30.755589v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5833600/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract Influenza A virus (IAV) defective interfering particles (DIPs) are regarded as promising broad-spectrum antivirals due to their high efficacy demonstrated in animal trials. Previously, an OP7 chimera DIP was generated that showed markedly enhanced antiviral efficacy compared to conventional IAV DIPs. In addition, a high-yield cell culture-based production process for OP7 chimera DIPs was established in perfusion mode. However, due to the technical complexity of this technology, we aimed to combine the advantages of perfusion in terms of yield with that of a simple and less complex batch process. In the present work, we established a fed-batch production process for OP7 chimera DIPs that allows a more straightforward implementation into existing production facilities. Using a feeding regime that was able to overcome the cell density effect, we achieved productive virus infection in stirred tank reactors until a cell density of 10E+6 cells/mL. Furthermore, we obtained a high virus titer of 3.8 log10(HAU/100 uL), corresponding to a 3.4-fold increase compared to a reference batch production. Moreover, the produced material demonstrated a significantly increased interfering bioactivity shown by an in vitro potency assay. Interestingly, this efficacy was similarly high as compared to OP7 chimera DIP material previously produced in perfusion mode, despite twofold lower virus titers. Finally, we demonstrate robustness of OP7 chimera DIP seed virus trains, which is significant step towards later pharmaceutical production. Further, corresponding GMP MDCK-PB2(sus) cell and OP7 chimera virus banks are now available for later biomanufacturing further use. In conclusion, the established fed-batch process offers a valid n additional option for pharmaceutical grade OP7 chimera DIP GMP manufacturing production under GMP conditions required for subsequent clinical testing and for later large-scale manufacturing. ### Competing Interest Statement A patent for the use of OP7 as an antiviral agent for treatment of IAV infection is approved for USA and pending for European Union and Japan. Patent holders are S.Y.K. and U.R. Another patent for the use of OP7 as an antiviral agent for treatment of coronavirus infection is pending. Patent holders are S.Y.K. and U.R. Besides, the authors declare no conflicts of interest. ## Funder Information Declared Max Planck Innovation, MTTADYSY006 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a [CC-BY 4.0 International license](http://creativecommons.org/licenses/by/4.0/). bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. 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[ Download PDF](https://www.biorxiv.org/content/10.64898/2026.09.30.755589v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/10/01/2026.09.30.755589.full.pdf)Full Text & In-line FiguresXML [More Info](https://www.biorxiv.org/about/FAQ#PrintOptions "More Information on Print/Save Options") [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) Fed-batch production of antiviral OP7 chimera defective interfering influenza A particles Wiebke Holste, Sascha Young Kupke, Claudius Seitz, Udo Reichl, Holger Ziehr bioRxiv 2026.09.30.755589; doi: https://doi.org/10.64898/2026.09.30.755589 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. 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