Development of high-growth influenza H7N9 prepandemic candidate vaccine viruses in suspension MDCK cells

Autor: Po-Ling Chen, Shin-Yi Tsai, Wang-Chou Sung, Chia-Chun Lai, Chia-Chun Lu, Alan Yung-Chih Hu, Ming-Tsan Liu, Min-Shi Lee, Hsin-I Chou, Pin-Wen Chen, Tsai-Teng Tzeng, Tsai-Chuan Weng
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Journal of Biomedical Science
Journal of Biomedical Science, Vol 27, Iss 1, Pp 1-11 (2020)
ISSN: 1423-0127
1021-7770
Popis: Background Influenza vaccine manufacturers traditionally use egg-derived candidate vaccine viruses (CVVs) to produce high-yield influenza viruses for seasonal or pandemic vaccines; however, these egg-derived CVVs need an adaptation process for the virus to grow in mammalian cells. The low yields of cell-based manufacturing systems using egg-derived CVVs remain an unsolved issue. This study aimed to develop high-growth cell-derived CVVs for MDCK cell-based vaccine manufacturing platforms. Methods Four H7N9 CVVs were generated in characterized Vero and adherent MDCK (aMDCK) cells. Furthermore, reassortant viruses were amplified in adherent MDCK (aMDCK) cells with certification, and their growth characteristics were detected in aMDCK cells and new suspension MDCK (sMDCK) cells. Finally, the plaque-forming ability, biosafety, and immunogenicity of H7N9 reassortant viruses were evaluated. Results The HA titers of these CVVs produced in proprietary suspension MDCK (sMDCK) cells and chicken embryos were 2- to 8-fold higher than those in aMDCK cells. All H7N9 CVVs showed attenuated characteristics by trypsin-dependent plaque assay and chicken embryo lethality test. The alum-adjuvanted NHRI-RG5 (derived from the fifth wave H7N9 virus A/Guangdong/SP440/2017) vaccine had the highest immunogenicity and cross-reactivity among the four H7N9 CVVs. Finally, we found that AddaVax adjuvant improved the cross-reactivity of low pathogenic H7N9 virus against highly pathogenic H7N9 viruses. Conclusions Our study indicates that cell-derived H7N9 CVVs possessed high growth rate in new sMDCK cells and low pathogenicity in chicken embryo, and that CVVs generated by this platform are also suitable for both cell- and egg-based prepandemic vaccine production.
Databáze: OpenAIRE