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Yellow fever virus (YFV) is the causative agent of yellow fever that can cause death
when it infects a person.
Although an attenuated vaccine (YFV 17D) is available, vaccine shortages and insufficient vaccination rates lead to frequent disease outbreaks, and non-immune individuals remain at risk
.
At present, there is no specific drug
available clinically for the treatment of yellow fever.
The research team of the Institute of Microbiology provided clinical candidates for the treatment or prevention of yellow fever, and analyzed its mechanism of action at the molecular level to discover a super-neutralizing epitope that provides an ideal target for epitope-based vaccine design
.
In this study, 8 strains of antibodies bound to YFV-E protein were obtained, of which 2 strains had super neutralizing activity and had a highly effective therapeutic effect
on mice infected with yellow fever virus.
From the complex structure, it was found that the binding sites of the two strains of antibodies overlapped with the binding sites of viral prM protein, and it was verified by functional experiments that the two strains of antibodies could bind to E protein in both pre-fusion and post-fusion conformation.
The mechanism plays a neutralizing role
.
In addition, further functional experiments showed that the binding site of the two is a super-neutralizing epitope of yellow fever virus, that is, the antibody that recognizes this epitope has a small content in patients recovering from yellow fever, but it plays an efficient neutralizing role
.
The findings have been published online in The Innovation
.
Associate researcher Li Yan of the Institute of Microbiology, Chinese Academy of Sciences, Professor Chen Zhihai of Beijing Ditan Hospital affiliated to Capital Medical University, postdoctoral fellow Tong Lili and researcher Dai Lianpan of the Institute of Microbiology of the Chinese Academy of Sciences are the joint first authors of the paper, and Academician Gao Fu and researcher Yan Jinghua of the Institute of Microbiology of the Chinese Academy of Sciences are the co-corresponding authors
.
This work was supported by the National Key R&D Program, the Strategic Leading Science and Technology Special Project of the Chinese Academy of Sciences (Category B), the National Natural Science Foundation of China, and the Youth Innovation Promotion Association of the Chinese Academy of Sciences.
Article link: https://doi.
org/10.
1016/j.
xinn.
2022.
100323
