Construction of a Vero cell line expression human KREMEN1 for the development of CVA6 vaccines
Abstract Coxsackievirus A6 (CVA6) has emerged as a major pathogen causing hand, foot and mouth disease (HFMD) outbreaks worldwide. The CVA6 epidemic poses a new challenge in HFMD control since there is currently no vaccine available against CVA6 infections. The Vero cell line has been widely used in...
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BMC
2025-01-01
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| Series: | Virology Journal |
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| Online Access: | https://doi.org/10.1186/s12985-024-02618-1 |
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| author | Dongqing Zhang Yuxiang Zou Jiaying Wu Longfa Xu Zhifeng Ke Yuanyuan Wu Zhenhong Zhou Mujin Fang Ling Chen Henggang Xu Jianping Chu Ningshao Xia Rui Zhu Tong Cheng |
| author_facet | Dongqing Zhang Yuxiang Zou Jiaying Wu Longfa Xu Zhifeng Ke Yuanyuan Wu Zhenhong Zhou Mujin Fang Ling Chen Henggang Xu Jianping Chu Ningshao Xia Rui Zhu Tong Cheng |
| author_sort | Dongqing Zhang |
| collection | DOAJ |
| description | Abstract Coxsackievirus A6 (CVA6) has emerged as a major pathogen causing hand, foot and mouth disease (HFMD) outbreaks worldwide. The CVA6 epidemic poses a new challenge in HFMD control since there is currently no vaccine available against CVA6 infections. The Vero cell line has been widely used in vaccine production, particularly in the preparation of viral vaccines, including poliovirus vaccines and EV71 vaccines. Unfortunately, most CVA6 strains failed to propagate effectively on Vero cells. The expression level of virus-specific receptors on the cell membrane significantly influences viral infection. Here, a Vero cell line with stable over-expressing of KREMEN1 (KRM1), a crucial receptor for CVA6, was constructed using the lentivirus system. The cloned cell line, called Vero-KRM1_#11, could efficiently support most CVA6 infections. The propagation of CVA6-TW00141 strain on Vero-KRM1_#11 was equal to that on RD cells. After four passages, the virus batch was obtained with a titer of about 107 TCID50/mL. Moreover, the purified CVA6 particles produced from Vero-KRM1_#11 or RD cells both could induce high and comparable levels of IgG and neutralizing antibodies. Importantly, passive transfer of the antisera from CVA6-vaccined mice showed 100% preventive efficacy against CVA6 infection in mice. Therefore, KRM1-expressing cells have the potential to serve as a valuable tool for the development and production of CVA6 or polyvalent HFMD vaccines. |
| format | Article |
| id | doaj-art-012432ad476440f1993e10503a1e9ff4 |
| institution | Kabale University |
| issn | 1743-422X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Virology Journal |
| spelling | doaj-art-012432ad476440f1993e10503a1e9ff42025-01-19T12:10:15ZengBMCVirology Journal1743-422X2025-01-0122111210.1186/s12985-024-02618-1Construction of a Vero cell line expression human KREMEN1 for the development of CVA6 vaccinesDongqing Zhang0Yuxiang Zou1Jiaying Wu2Longfa Xu3Zhifeng Ke4Yuanyuan Wu5Zhenhong Zhou6Mujin Fang7Ling Chen8Henggang Xu9Jianping Chu10Ningshao Xia11Rui Zhu12Tong Cheng13State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen UniversityDepartment of Pediatrics, Zhongshan Hospital, Xiamen UniversityBeijing Wantai Biological Pharmacy Enterprise Co., LtdBeijing Wantai Biological Pharmacy Enterprise Co., LtdState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen UniversityAbstract Coxsackievirus A6 (CVA6) has emerged as a major pathogen causing hand, foot and mouth disease (HFMD) outbreaks worldwide. The CVA6 epidemic poses a new challenge in HFMD control since there is currently no vaccine available against CVA6 infections. The Vero cell line has been widely used in vaccine production, particularly in the preparation of viral vaccines, including poliovirus vaccines and EV71 vaccines. Unfortunately, most CVA6 strains failed to propagate effectively on Vero cells. The expression level of virus-specific receptors on the cell membrane significantly influences viral infection. Here, a Vero cell line with stable over-expressing of KREMEN1 (KRM1), a crucial receptor for CVA6, was constructed using the lentivirus system. The cloned cell line, called Vero-KRM1_#11, could efficiently support most CVA6 infections. The propagation of CVA6-TW00141 strain on Vero-KRM1_#11 was equal to that on RD cells. After four passages, the virus batch was obtained with a titer of about 107 TCID50/mL. Moreover, the purified CVA6 particles produced from Vero-KRM1_#11 or RD cells both could induce high and comparable levels of IgG and neutralizing antibodies. Importantly, passive transfer of the antisera from CVA6-vaccined mice showed 100% preventive efficacy against CVA6 infection in mice. Therefore, KRM1-expressing cells have the potential to serve as a valuable tool for the development and production of CVA6 or polyvalent HFMD vaccines.https://doi.org/10.1186/s12985-024-02618-1Coxsackievirus A6Vero cell lineHuman KREMEN1 receptorVaccine |
| spellingShingle | Dongqing Zhang Yuxiang Zou Jiaying Wu Longfa Xu Zhifeng Ke Yuanyuan Wu Zhenhong Zhou Mujin Fang Ling Chen Henggang Xu Jianping Chu Ningshao Xia Rui Zhu Tong Cheng Construction of a Vero cell line expression human KREMEN1 for the development of CVA6 vaccines Virology Journal Coxsackievirus A6 Vero cell line Human KREMEN1 receptor Vaccine |
| title | Construction of a Vero cell line expression human KREMEN1 for the development of CVA6 vaccines |
| title_full | Construction of a Vero cell line expression human KREMEN1 for the development of CVA6 vaccines |
| title_fullStr | Construction of a Vero cell line expression human KREMEN1 for the development of CVA6 vaccines |
| title_full_unstemmed | Construction of a Vero cell line expression human KREMEN1 for the development of CVA6 vaccines |
| title_short | Construction of a Vero cell line expression human KREMEN1 for the development of CVA6 vaccines |
| title_sort | construction of a vero cell line expression human kremen1 for the development of cva6 vaccines |
| topic | Coxsackievirus A6 Vero cell line Human KREMEN1 receptor Vaccine |
| url | https://doi.org/10.1186/s12985-024-02618-1 |
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