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

Wang, Qi; Chen, Tuanjie; Feng, Mengru; Zheng, Mei; Gao, Feixia; Qiu, Chenchen; Luo, Jian; Li, Xiuling

doi:10.3390/v17081097

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Open AccessArticle

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

by

Qi Wang

,

Tuanjie Chen

,

Mengru Feng

,

Mei Zheng

,

Feixia Gao

,

Chenchen Qiu

,

Jian Luo

^*

and

Xiuling Li

^*

Department of Virus and Vaccine, Shanghai Institute of Biological Products, Shanghai 200052, China

^*

Authors to whom correspondence should be addressed.

Viruses 2025, 17(8), 1097; https://doi.org/10.3390/v17081097

Submission received: 18 July 2025 / Revised: 6 August 2025 / Accepted: 7 August 2025 / Published: 8 August 2025

(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)

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Abstract

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.

Keywords: IFNAR1; influenza vaccine; MDCK cells; interferon; CRISPR/Cas9

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MDPI and ACS Style

Wang, Q.; Chen, T.; Feng, M.; Zheng, M.; Gao, F.; Qiu, C.; Luo, J.; Li, X. Deficiency of IFNAR1 Increases the Production of Influenza Vaccine Viruses in MDCK Cells. Viruses 2025, 17, 1097. https://doi.org/10.3390/v17081097

AMA Style

Wang Q, Chen T, Feng M, Zheng M, Gao F, Qiu C, Luo J, Li X. Deficiency of IFNAR1 Increases the Production of Influenza Vaccine Viruses in MDCK Cells. Viruses. 2025; 17(8):1097. https://doi.org/10.3390/v17081097

Chicago/Turabian Style

Wang, Qi, Tuanjie Chen, Mengru Feng, Mei Zheng, Feixia Gao, Chenchen Qiu, Jian Luo, and Xiuling Li. 2025. "Deficiency of IFNAR1 Increases the Production of Influenza Vaccine Viruses in MDCK Cells" Viruses 17, no. 8: 1097. https://doi.org/10.3390/v17081097

APA Style

Wang, Q., Chen, T., Feng, M., Zheng, M., Gao, F., Qiu, C., Luo, J., & Li, X. (2025). Deficiency of IFNAR1 Increases the Production of Influenza Vaccine Viruses in MDCK Cells. Viruses, 17(8), 1097. https://doi.org/10.3390/v17081097

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

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