A safer cell-based yellow fever live attenuated vaccine protects mice against YFV infection

• Published in: iScience 2024-10, Vol.27 (10), p.110972, Article 110972
• Main Authors: Guo, Weiwei, Jiang, Tingting, Rao, Juhong, Zhang, Zihan, Zhang, Xuekai, Su, Jiaoling, Yin, Chunhong, Lu, Mingqing, Hu, Xue, Shan, Chao
• Format: Article
• Language: English
• Subjects: Health sciences; Immunology; Virology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.110972

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. [Display omitted] •Deletions in the 3′UTR of the YF17D genome led to further attenuation of the virus•A single dose of YF17D-Δ77 provides complete and long-lasting immune protection•YF7D-Δ77 exhibits equivalent immunogenicity and efficacy in mice•YF17D-Δ77 showed strong genetic stability after 20-round passage in cell culture Health sciences; Virology; Immunology