Deficiency of IFNAR1 Increases the Production of Influenza Vaccine Viruses in MDCK Cells

Cell culture-based influenza vaccines exhibit comparable safety and immunogenicity to traditional egg-based vaccines. However, improving viral yield remains a key challenge in optimizing cell culture-based production systems. Madin–Darby canine kidney (MDCK) cells, the predominant cell line for infl...

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Bibliographic Details
Published in:Viruses Vol. 17; no. 8; p. 1097
Main Authors: Wang, Qi, Chen, Tuanjie, Feng, Mengru, Zheng, Mei, Gao, Feixia, Qiu, Chenchen, Luo, Jian, Li, Xiuling
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 08.08.2025
MDPI
Subjects:
Animals
Antibodies
Biological response modifiers
Cell culture
CRISPR
CRISPR-Cas Systems
CRISPR/Cas9
Dogs
Down-regulation
Ethylenediaminetetraacetic acid
Gene Knockout Techniques
Genes
IFNAR1
Immunogenicity
Infections
Influenza
Influenza A Virus, H1N1 Subtype - growth & development
Influenza A Virus, H1N1 Subtype - immunology
Influenza A Virus, H3N2 Subtype - immunology
influenza vaccine
Influenza vaccines
Influenza Vaccines - immunology
Interferon
Madin Darby Canine Kidney Cells
Manufacturing
MDCK cells
Microenvironments
Plasmids
Receptor, Interferon alpha-beta - deficiency
Receptor, Interferon alpha-beta - genetics
Replication
Signal transduction
Transcriptomics
Vaccines
Viral infections
Virus Cultivation - methods
Virus Replication
Viruses
United States
China
Beijing China
United States > US
Shanghai China
influenza vaccine
CRISPR/Cas9
MDCK cells
interferon
IFNAR1
ISSN:1999-4915, 1999-4915
Online Access:Get full text
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Summary:Cell culture-based influenza vaccines exhibit comparable safety and immunogenicity to traditional egg-based vaccines. However, improving viral yield remains a key challenge in optimizing cell culture-based production systems. Madin–Darby canine kidney (MDCK) cells, the predominant cell line for influenza vaccine production, inherently activate interferon (IFN)-mediated antiviral defenses that restrict viral replication. To overcome this limitation, we employed CRISPR/Cas9 gene-editing technology to generate an IFN alpha/beta receptor subunit 1 (IFNAR1)-knockout (KO) adherent MDCK cell line. Viral titer analysis demonstrated significant enhancements in the yield of multiple vaccine strains (H1N1, H3N2, and type B) in IFNAR1-KO cells compared to wild-type (WT) cells. Transcriptomic profiling revealed marked downregulation of key interferon-stimulated genes (ISGs)—including OAS, MX2, and ISG15—within the IFNAR1-KO cells, indicating a persistent suppression of antiviral responses that established a more permissive microenvironment for influenza virus replication. Collectively, the engineered IFNAR1-KO cell line provides a valuable tool for influenza virus research and a promising strategy for optimizing large-scale MDCK cell cultures to enhance vaccine production efficiency.
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ISSN:1999-4915
1999-4915
DOI:10.3390/v17081097