Characterization and Immunogenicity of Influenza H7N9 Vaccine Antigens Produced Using a Serum-Free Suspension MDCK Cell-Based Platform

Human infections with avian-origin H7N9 influenza A viruses were first reported in China, and an approximately 38% human mortality rate was described across six waves from February 2013 to September 2018. Vaccination is one of the most cost-effective ways to reduce morbidity and mortality during inf...

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Main Authors: Min-Yuan Chia, Chun-Yang Lin, Po-Ling Chen, Chia-Chun Lai, Tsai-Chuan Weng, Wang-Chou Sung, Alan Yung-Chih Hu, Min-Shi Lee
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/14/9/1937
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author Min-Yuan Chia
Chun-Yang Lin
Po-Ling Chen
Chia-Chun Lai
Tsai-Chuan Weng
Wang-Chou Sung
Alan Yung-Chih Hu
Min-Shi Lee
author_facet Min-Yuan Chia
Chun-Yang Lin
Po-Ling Chen
Chia-Chun Lai
Tsai-Chuan Weng
Wang-Chou Sung
Alan Yung-Chih Hu
Min-Shi Lee
author_sort Min-Yuan Chia
collection DOAJ
description Human infections with avian-origin H7N9 influenza A viruses were first reported in China, and an approximately 38% human mortality rate was described across six waves from February 2013 to September 2018. Vaccination is one of the most cost-effective ways to reduce morbidity and mortality during influenza epidemics and pandemics. Egg-based platforms for the production of influenza vaccines are labor-intensive and unable to meet the surging demand during pandemics. Therefore, cell culture-based technology is becoming the alternative strategy for producing influenza vaccines. The current influenza H7N9 vaccine virus (NIBRG-268), a reassortant virus from A/Anhui/1/2013 (H7N9) and egg-adapted A/PR/8/34 (H1N1) viruses, could grow efficiently in embryonated eggs but not mammalian cells. Moreover, a freezing-dry formulation of influenza H7N9 vaccines with long-term stability will be desirable for pandemic preparedness, as the occurrence of influenza H7N9 pandemics is not predictable. In this study, we adapted a serum-free anchorage-independent suspension Madin-Darby Canine Kidney (MDCK) cell line for producing influenza H7N9 vaccines and compared the biochemical characteristics and immunogenicity of three influenza H7N9 vaccine antigens produced using the suspension MDCK cell-based platform without freeze-drying (S-WO-H7N9), the suspension MDCK cell-based platform with freeze-drying (S-W-H7N9) or the egg-based platform with freeze-drying (E-W-H7N9). We demonstrated these three vaccine antigens have comparable biochemical characteristics. In addition, these three vaccine antigens induced robust and comparable neutralizing antibody (NT; geometric mean between 1016 and 4064) and hemagglutinin-inhibition antibody (HI; geometric mean between 640 and 1613) titers in mice. In conclusion, the serum-free suspension MDCK cell-derived freeze-dried influenza H7N9 vaccine is highly immunogenic in mice, and clinical development is warranted.
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spelling doaj.art-57ea496f076d40e39ec5652f6f90d8ab2023-11-23T19:26:44ZengMDPI AGViruses1999-49152022-08-01149193710.3390/v14091937Characterization and Immunogenicity of Influenza H7N9 Vaccine Antigens Produced Using a Serum-Free Suspension MDCK Cell-Based PlatformMin-Yuan Chia0Chun-Yang Lin1Po-Ling Chen2Chia-Chun Lai3Tsai-Chuan Weng4Wang-Chou Sung5Alan Yung-Chih Hu6Min-Shi Lee7Department of Veterinary Medicine, National Chung Hsing University, Taichung 40227, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan 35053, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan 35053, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan 35053, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan 35053, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan 35053, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan 35053, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan 35053, TaiwanHuman infections with avian-origin H7N9 influenza A viruses were first reported in China, and an approximately 38% human mortality rate was described across six waves from February 2013 to September 2018. Vaccination is one of the most cost-effective ways to reduce morbidity and mortality during influenza epidemics and pandemics. Egg-based platforms for the production of influenza vaccines are labor-intensive and unable to meet the surging demand during pandemics. Therefore, cell culture-based technology is becoming the alternative strategy for producing influenza vaccines. The current influenza H7N9 vaccine virus (NIBRG-268), a reassortant virus from A/Anhui/1/2013 (H7N9) and egg-adapted A/PR/8/34 (H1N1) viruses, could grow efficiently in embryonated eggs but not mammalian cells. Moreover, a freezing-dry formulation of influenza H7N9 vaccines with long-term stability will be desirable for pandemic preparedness, as the occurrence of influenza H7N9 pandemics is not predictable. In this study, we adapted a serum-free anchorage-independent suspension Madin-Darby Canine Kidney (MDCK) cell line for producing influenza H7N9 vaccines and compared the biochemical characteristics and immunogenicity of three influenza H7N9 vaccine antigens produced using the suspension MDCK cell-based platform without freeze-drying (S-WO-H7N9), the suspension MDCK cell-based platform with freeze-drying (S-W-H7N9) or the egg-based platform with freeze-drying (E-W-H7N9). We demonstrated these three vaccine antigens have comparable biochemical characteristics. In addition, these three vaccine antigens induced robust and comparable neutralizing antibody (NT; geometric mean between 1016 and 4064) and hemagglutinin-inhibition antibody (HI; geometric mean between 640 and 1613) titers in mice. In conclusion, the serum-free suspension MDCK cell-derived freeze-dried influenza H7N9 vaccine is highly immunogenic in mice, and clinical development is warranted.https://www.mdpi.com/1999-4915/14/9/1937influenza H7N9 vaccinesuspension MDCK cellimmunogenicity
spellingShingle Min-Yuan Chia
Chun-Yang Lin
Po-Ling Chen
Chia-Chun Lai
Tsai-Chuan Weng
Wang-Chou Sung
Alan Yung-Chih Hu
Min-Shi Lee
Characterization and Immunogenicity of Influenza H7N9 Vaccine Antigens Produced Using a Serum-Free Suspension MDCK Cell-Based Platform
Viruses
influenza H7N9 vaccine
suspension MDCK cell
immunogenicity
title Characterization and Immunogenicity of Influenza H7N9 Vaccine Antigens Produced Using a Serum-Free Suspension MDCK Cell-Based Platform
title_full Characterization and Immunogenicity of Influenza H7N9 Vaccine Antigens Produced Using a Serum-Free Suspension MDCK Cell-Based Platform
title_fullStr Characterization and Immunogenicity of Influenza H7N9 Vaccine Antigens Produced Using a Serum-Free Suspension MDCK Cell-Based Platform
title_full_unstemmed Characterization and Immunogenicity of Influenza H7N9 Vaccine Antigens Produced Using a Serum-Free Suspension MDCK Cell-Based Platform
title_short Characterization and Immunogenicity of Influenza H7N9 Vaccine Antigens Produced Using a Serum-Free Suspension MDCK Cell-Based Platform
title_sort characterization and immunogenicity of influenza h7n9 vaccine antigens produced using a serum free suspension mdck cell based platform
topic influenza H7N9 vaccine
suspension MDCK cell
immunogenicity
url https://www.mdpi.com/1999-4915/14/9/1937
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