Viruses are attenuated for vaccines through serial passage or chemical mutagenesis
Multiple studies demonstrate that viral attenuation for live vaccines is commonly achieved through techniques such as serial passage in cell cultures or developing specific mutations.
The retrieved papers consistently support the claim that viruses are attenuated for vaccines through serial passage (e.g., in Japanese encephalitis, duck hepatitis A, African swine fever, Powassan virus, and yellow fever). Although chemical mutagenesis is not the primary focus of every paper, the extensive documentation of serial passage directly confirms the core mechanism stated in the claim without any refuting evidence.
Sang-Im Yun, B. Song, Jin-Kyoung Kim, G. Yun, Eun-Young Lee, Long Li, R. Kuhn, M. Rossmann, J. Morrey, Young-Min Lee. A Molecularly Cloned, Live-Attenuated Japanese Encephalitis Vaccine SA14-14-2 Virus: A Conserved Single Amino Acid in the ij Hairpin of the Viral E Glycoprotein Determines Neurovirulence in Mice. 2014. https://doi.org/10.1371/journal.ppat.1004290
Paper [1] describes deriving live-attenuated Japanese encephalitis vaccine strains via serial intracerebral passage.
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Jinyan Xie, Mingshu Wang, A. Cheng, Xinxin Zhao, Mafeng Liu, Dekang Zhu, Shun Chen, R. Jia, Qiao Yang, Ying Wu, Shaqiu Zhang, Yunya Liu, Yanling Yu, Ling Zhang, Xiaoyue Chen. DHAV-1 Inhibits Type I Interferon Signaling to Assist Viral Adaption by Increasing the Expression of SOCS3. 2019. https://doi.org/10.3389/fimmu.2019.00731
Paper [2] notes that the attenuated duck hepatitis A vaccine strain is cultivated through serial passage in chicken embryos.
Xiaoyu Zhang, Zhenzhong Wang, Shengqiang Ge, Yuanyuan Zuo, Haodong Lu, Y. Lv, Naijun Han, Yumei Cai, Xiao-dong Wu, Zhiliang Wang. Attenuated African swine fever virus through serial passaging of viruses in cell culture: a brief review on the knowledge gathered during 60 years of research. 2022. https://doi.org/10.1007/s11262-022-01939-z
Paper [4] reviews the production of attenuated African swine fever virus strains through serial passaging in cell culture.
Grace E. Himmler, Megan C. Mladinich, Jonas N. Conde, E. Gorbunova, M. Lindner, Hwan Keun Kim, E. Mackow. Passage-attenuated Powassan virus LI9P protects mice from lethal LI9 challenge and links envelope residue D308 to neurovirulence. 2025. https://doi.org/10.1128/mbio.00065-25
Paper [9] reports isolating an attenuated Powassan virus strain via serial passage in cell culture.
Xueer Qiu, Adam L. Bailey. Two mutations in NS2B are responsible for attenuation of the yellow fever virus (YFV) vaccine strain 17D. 2025. https://doi.org/10.1371/journal.ppat.1013373
Paper [11] details how the classic yellow fever 17D vaccine was developed through extensive serial passage of the virulent Asibi strain.
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