tetano
Editor, Senior Moderator
Open Life Sci
. 2022 Sep 26;17(1):1282-1295.
doi: 10.1515/biol-2022-0478. eCollection 2022.
Preclinical immunogenicity assessment of a cell-based inactivated whole-virion H5N1 influenza vaccine
Zhegang Zhang[SUP] 1 2 [/SUP], Zheng Jiang[SUP] 3 [/SUP], Tao Deng[SUP] 1 2 [/SUP], Jiayou Zhang[SUP] 1 2 [/SUP], Bo Liu[SUP] 1 2 [/SUP], Jing Liu[SUP] 1 2 [/SUP], Ran Qiu[SUP] 1 2 [/SUP], Qingmei Zhang[SUP] 1 2 [/SUP], Xuedan Li[SUP] 1 2 [/SUP], Xuanxuan Nian[SUP] 1 2 [/SUP], Yue Hong[SUP] 1 2 [/SUP], Fang Li[SUP] 1 2 [/SUP], Feixia Peng[SUP] 1 2 [/SUP], Wei Zhao[SUP] 1 [/SUP], Zhiwu Xia[SUP] 1 [/SUP], Shihe Huang[SUP] 1 [/SUP], Shuyan Liang[SUP] 4 [/SUP], Jinhua Chen[SUP] 1 2 [/SUP], Changgui Li[SUP] 3 [/SUP], Xiaoming Yang[SUP] 2 5 [/SUP]
Affiliations
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.
Keywords: H5N1; MDCK cells; cellular immune response; humoral immune response; vaccine.
. 2022 Sep 26;17(1):1282-1295.
doi: 10.1515/biol-2022-0478. eCollection 2022.
Preclinical immunogenicity assessment of a cell-based inactivated whole-virion H5N1 influenza vaccine
Zhegang Zhang[SUP] 1 2 [/SUP], Zheng Jiang[SUP] 3 [/SUP], Tao Deng[SUP] 1 2 [/SUP], Jiayou Zhang[SUP] 1 2 [/SUP], Bo Liu[SUP] 1 2 [/SUP], Jing Liu[SUP] 1 2 [/SUP], Ran Qiu[SUP] 1 2 [/SUP], Qingmei Zhang[SUP] 1 2 [/SUP], Xuedan Li[SUP] 1 2 [/SUP], Xuanxuan Nian[SUP] 1 2 [/SUP], Yue Hong[SUP] 1 2 [/SUP], Fang Li[SUP] 1 2 [/SUP], Feixia Peng[SUP] 1 2 [/SUP], Wei Zhao[SUP] 1 [/SUP], Zhiwu Xia[SUP] 1 [/SUP], Shihe Huang[SUP] 1 [/SUP], Shuyan Liang[SUP] 4 [/SUP], Jinhua Chen[SUP] 1 2 [/SUP], Changgui Li[SUP] 3 [/SUP], Xiaoming Yang[SUP] 2 5 [/SUP]
Affiliations
- PMID: 36249527
- PMCID: PMC9518664
- DOI: 10.1515/biol-2022-0478
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.
Keywords: H5N1; MDCK cells; cellular immune response; humoral immune response; vaccine.