Recently, the foot-and-mouth disease prevention and control technical team of the Lanzhou Institute of Veterinary Medicine of the Chinese Academy of Agricultural Sciences, together with the research team of Wang Xiangxi from the Institute of Biophysics of the Chinese Academy of Sciences, and the Wageningen Institute of Biology and Veterinary Medicine in the Netherlands, broke through the three-dimensional structure of the virus antibody complex. The bottleneck that is difficult to improve the resolution, high resolution is passed for the first time (～3.1 Å) The atomic structure reveals the antiviral mechanism of the neutralizing antibody of the foot-and-mouth disease virus, and provides theoretical guidance and important biological materials for the design of the foot-and-mouth disease broad-spectrum vaccine and the quality monitoring of the foot-and-mouth disease vaccine. Relevant research results were published online in”Protein and Cell” on February 18.
According to researcher Guo Huichen, the head of the foot-and-mouth disease prevention and control technical team, foot-and-mouth disease, as a severe animal infectious disease that must be reported in my country, threatens the healthy and sustainable development of animal husbandry. Inactivated vaccines are still one of the effective means to prevent and control foot-and-mouth disease, but the effective antigen (146S) content of foot-and-mouth disease virus in inactivated vaccines is the key to determining vaccine quality. How to establish a highly sensitive and highly specific vaccine evaluation system is current One of the important points; in addition, the seven serotypes of foot-and-mouth disease virus lack cross-protection. How to obtain a broad-spectrum vaccine against multiple serotypes of foot-and-mouth disease is also the focus of current foot-and-mouth disease research, while the specific neutralizing antibody of foot-and-mouth disease virus solves the above problem. The best choice for scientific issues.
The research team first confirmed through in vivo and in vitro experiments that two foot-and-mouth disease-specific antibodies have high-efficiency neutralization activity. Among them, the M8 antibody has a broad-spectrum neutralization effect against a variety of foot-and-mouth disease serotypes, and the M170 antibody specifically recognizes type O Neutralizing properties of foot-and-mouth disease virus (146S). Subsequently, cryogenic cryo-electron microscopy single particle reconstruction technology was used to analyze the high-resolution three-dimensional structure of the two strains of neutralizing antibody and foot-and-mouth disease virus complexes. Through molecular structure and multiple sequence comparison analysis, it was determined that the M8 neutralizing antibody was bound to the virus coat. The GH-loop and EF-loop regions of the shell protein monomer molecules specifically recognize the spatial conformational epitope composed of VP1 and VP3, and this epitope is extremely conserved among the seven serotypes of foot-and-mouth disease virus, indicating that the antibody has broad-spectrum recognition Characteristics, this has extremely important reference value for obtaining a broad-spectrum foot-and-mouth disease prevention and control agent; M170 neutralizing antibody specifically binds to the secondary axis of the O-type foot-and-mouth disease virus capsid, because the cleavage of the capsid will cause amino acid rearrangement near the secondary axis. As a result, M170 cannot recognize the 12S monomer produced by the cleavage of intact virus particles (146S), indicating that the antibody has the recognition characteristics of O-type foot-and-mouth disease virus 146S, which can provide a very effective tool for the establishment of the current inactivated foot-and-mouth disease vaccine quality evaluation system. This research is the only innovative research result that has explained the neutralization mechanism of foot-and-mouth disease virus with high resolution so far.
The research was jointly funded by the National Key Research and Development Program, the National Natural Science Foundation of China, and the Science and Technology Innovation Project of the Chinese Academy of Agricultural Sciences.
related paper information:http://doi.org/10.1007/s13238-021-00828-9