A safer cell-based yellow fever live attenuated vaccine protects mice against YFV infection
Weiwei Guo,
Tingting Jiang,
Juhong Rao,
Zihan Zhang,
Xuekai Zhang,
Jiaoling Su,
Chunhong Yin,
Mingqing Lu,
Xue Hu,
Chao Shan
Affiliations
Weiwei Guo
Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of the Chinese Academy of Sciences, Beijing 100039, China
Tingting Jiang
Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China
Juhong Rao
Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of the Chinese Academy of Sciences, Beijing 100039, China
Zihan Zhang
Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of the Chinese Academy of Sciences, Beijing 100039, China
Xuekai Zhang
Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of the Chinese Academy of Sciences, Beijing 100039, China
Jiaoling Su
Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of the Chinese Academy of Sciences, Beijing 100039, China
Chunhong Yin
Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China
Mingqing Lu
Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of the Chinese Academy of Sciences, Beijing 100039, China
Xue Hu
Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China
Chao Shan
Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of the Chinese Academy of Sciences, Beijing 100039, China; Hubei Jiangxia Laboratory, Wuhan 430200, China; Corresponding author
Summary: The live attenuated yellow fever vaccine (YF17D) has caused controversial safety issues in history with low-yield problems, which has led to a large population being unable to be vaccinated and vaccine shortage in facing recent outbreaks. Here, we report a safer live attenuated vaccine candidate, YF17D-Δ77, which contains 77 nucleotides deletion in the 3′ untranslated region (3′ UTR) of the YF17D genome. YF17D-Δ77 exhibited no neurotropism and decreased viscerotropism and caused significantly lower lethality in mice compared to YF17D. Mechanistically, the deletion enhanced the sensitivity of the virus to type I and type II interferon responses, which hindered viral replication. Encouragingly, YF17D-Δ77 provided comparable immune protection in mice as did YF17D. Even 10 PFU of YF17D-Δ77 completely protected mice against YFV-Asibi challenge. In addition, the Δ77 mutation showed excellent stability after successive passages in Vero cells. Collectively, the data suggest that further development of YF17D-Δ77 as vaccine candidate is warranted.
