Preclinical immunogenicity assessment of a cell-based inactivated whole-virion H5N1 influenza vaccine
In influenza vaccine development, Madin–Darby canine kidney (MDCK) cells provide multiple advantages, including large-scale production and egg independence. Several cell-based influenza vaccines have been approved worldwide. We cultured H5N1 virus in a serum-free MDCK cell suspension. The harvested...
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De Gruyter
2022-09-01
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Series: | Open Life Sciences |
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Online Access: | https://doi.org/10.1515/biol-2022-0478 |
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author | Zhang Zhegang Jiang Zheng Deng Tao Zhang Jiayou Liu Bo Liu Jing Qiu Ran Zhang Qingmei Li Xuedan Nian Xuanxuan Hong Yue Li Fang Peng Feixia Zhao Wei Xia Zhiwu Huang Shihe Liang Shuyan Chen Jinhua Li Changgui Yang Xiaoming |
author_facet | Zhang Zhegang Jiang Zheng Deng Tao Zhang Jiayou Liu Bo Liu Jing Qiu Ran Zhang Qingmei Li Xuedan Nian Xuanxuan Hong Yue Li Fang Peng Feixia Zhao Wei Xia Zhiwu Huang Shihe Liang Shuyan Chen Jinhua Li Changgui Yang Xiaoming |
author_sort | Zhang Zhegang |
collection | DOAJ |
description | In influenza vaccine development, Madin–Darby canine kidney (MDCK) cells provide multiple advantages, including large-scale production and egg independence. Several cell-based influenza vaccines have been approved worldwide. We cultured H5N1 virus in a serum-free MDCK cell suspension. The harvested virus was manufactured into vaccines after inactivation and purification. The vaccine effectiveness was assessed in the Wuhan Institute of Biological Products BSL2 facility. The pre- and postvaccination mouse serum titers were determined using the microneutralization and hemagglutination inhibition tests. The immunological responses induced by vaccine were investigated using immunological cell classification, cytokine expression quantification, and immunoglobulin G (IgG) subtype classification. The protective effect of the vaccine in mice was evaluated using challenge test. Antibodies against H5N1 in rats lasted up to 8 months after the first dose. Compared with those of the placebo group, the serum titer of vaccinated mice increased significantly, Th1 and Th2 cells were activated, and CD8+ T cells were activated in two dose groups. Furthermore, the challenge test showed that vaccination reduced the clinical symptoms and virus titer in the lungs of mice after challenge, indicating a superior immunological response. Notably, early after vaccination, considerably increased interferon-inducible protein-10 (IP-10) levels were found, indicating improved vaccine-induced innate immunity. However, IP-10 is an adverse event marker, which is a cause for concern. Overall, in the case of an outbreak, the whole-virion H5N1 vaccine should provide protection. |
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spelling | doaj.art-01fadf6e0a184643963d1152e2b8739c2022-12-22T03:50:41ZengDe GruyterOpen Life Sciences2391-54122022-09-011711282129510.1515/biol-2022-0478Preclinical immunogenicity assessment of a cell-based inactivated whole-virion H5N1 influenza vaccineZhang Zhegang0Jiang Zheng1Deng Tao2Zhang Jiayou3Liu Bo4Liu Jing5Qiu Ran6Zhang Qingmei7Li Xuedan8Nian Xuanxuan9Hong Yue10Li Fang11Peng Feixia12Zhao Wei13Xia Zhiwu14Huang Shihe15Liang Shuyan16Chen Jinhua17Li Changgui18Yang Xiaoming19Viral Vaccines Research and Development Department 2, Wuhan Institute of Biological Products Co., LTD, Wuhan, 430207, ChinaNational Institute of Food and Drug Control, Beijing, 100050, ChinaViral Vaccines Research and Development Department 2, Wuhan Institute of Biological Products Co., LTD, Wuhan, 430207, ChinaViral Vaccines Research and Development Department 2, Wuhan Institute of Biological Products Co., LTD, Wuhan, 430207, ChinaViral Vaccines Research and Development Department 2, Wuhan Institute of Biological Products Co., LTD, Wuhan, 430207, ChinaViral Vaccines Research and Development Department 2, Wuhan Institute of Biological Products Co., LTD, Wuhan, 430207, ChinaViral Vaccines Research and Development Department 2, Wuhan Institute of Biological Products Co., LTD, Wuhan, 430207, ChinaViral Vaccines Research and Development Department 2, Wuhan Institute of Biological Products Co., LTD, Wuhan, 430207, ChinaViral Vaccines Research and Development Department 2, Wuhan Institute of Biological Products Co., LTD, Wuhan, 430207, ChinaViral Vaccines Research and Development Department 2, Wuhan Institute of Biological Products Co., LTD, Wuhan, 430207, ChinaViral Vaccines Research and Development Department 2, Wuhan Institute of Biological Products Co., LTD, Wuhan, 430207, ChinaViral Vaccines Research and Development Department 2, Wuhan Institute of Biological Products Co., LTD, Wuhan, 430207, ChinaViral Vaccines Research and Development Department 2, Wuhan Institute of Biological Products Co., LTD, Wuhan, 430207, ChinaViral Vaccines Research and Development Department 2, Wuhan Institute of Biological Products Co., LTD, Wuhan, 430207, ChinaViral Vaccines Research and Development Department 2, Wuhan Institute of Biological Products Co., LTD, Wuhan, 430207, ChinaViral Vaccines Research and Development Department 2, Wuhan Institute of Biological Products Co., LTD, Wuhan, 430207, ChinaWuhan Biobank Co., Ltd, Wuhan, 430075, ChinaViral Vaccines Research and Development Department 2, Wuhan Institute of Biological Products Co., LTD, Wuhan, 430207, ChinaNational Institute of Food and Drug Control, Beijing, 100050, ChinaNational Engineering Technology Research Center of Combination Vaccines, China National Biotec Group, Wuhan, 430207, ChinaIn influenza vaccine development, Madin–Darby canine kidney (MDCK) cells provide multiple advantages, including large-scale production and egg independence. Several cell-based influenza vaccines have been approved worldwide. We cultured H5N1 virus in a serum-free MDCK cell suspension. The harvested virus was manufactured into vaccines after inactivation and purification. The vaccine effectiveness was assessed in the Wuhan Institute of Biological Products BSL2 facility. The pre- and postvaccination mouse serum titers were determined using the microneutralization and hemagglutination inhibition tests. The immunological responses induced by vaccine were investigated using immunological cell classification, cytokine expression quantification, and immunoglobulin G (IgG) subtype classification. The protective effect of the vaccine in mice was evaluated using challenge test. Antibodies against H5N1 in rats lasted up to 8 months after the first dose. Compared with those of the placebo group, the serum titer of vaccinated mice increased significantly, Th1 and Th2 cells were activated, and CD8+ T cells were activated in two dose groups. Furthermore, the challenge test showed that vaccination reduced the clinical symptoms and virus titer in the lungs of mice after challenge, indicating a superior immunological response. Notably, early after vaccination, considerably increased interferon-inducible protein-10 (IP-10) levels were found, indicating improved vaccine-induced innate immunity. However, IP-10 is an adverse event marker, which is a cause for concern. Overall, in the case of an outbreak, the whole-virion H5N1 vaccine should provide protection.https://doi.org/10.1515/biol-2022-0478mdck cellshumoral immune responsecellular immune responseh5n1vaccine |
spellingShingle | Zhang Zhegang Jiang Zheng Deng Tao Zhang Jiayou Liu Bo Liu Jing Qiu Ran Zhang Qingmei Li Xuedan Nian Xuanxuan Hong Yue Li Fang Peng Feixia Zhao Wei Xia Zhiwu Huang Shihe Liang Shuyan Chen Jinhua Li Changgui Yang Xiaoming Preclinical immunogenicity assessment of a cell-based inactivated whole-virion H5N1 influenza vaccine Open Life Sciences mdck cells humoral immune response cellular immune response h5n1 vaccine |
title | Preclinical immunogenicity assessment of a cell-based inactivated whole-virion H5N1 influenza vaccine |
title_full | Preclinical immunogenicity assessment of a cell-based inactivated whole-virion H5N1 influenza vaccine |
title_fullStr | Preclinical immunogenicity assessment of a cell-based inactivated whole-virion H5N1 influenza vaccine |
title_full_unstemmed | Preclinical immunogenicity assessment of a cell-based inactivated whole-virion H5N1 influenza vaccine |
title_short | Preclinical immunogenicity assessment of a cell-based inactivated whole-virion H5N1 influenza vaccine |
title_sort | preclinical immunogenicity assessment of a cell based inactivated whole virion h5n1 influenza vaccine |
topic | mdck cells humoral immune response cellular immune response h5n1 vaccine |
url | https://doi.org/10.1515/biol-2022-0478 |
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