1. Preclinical immunogenicity assessment of a cell-based inactivated whole-virion H5N1 influenza vaccine
- 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, and Yang Xiaoming
- Subjects
mdck cells ,humoral immune response ,cellular immune response ,h5n1 ,vaccine ,Biology (General) ,QH301-705.5 - Abstract
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.
- Published
- 2022
- Full Text
- View/download PDF