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具有四个基因敲除的结节性皮肤病病毒在体内减毒，并能保护牛免受感染。

Lumpy Skin Disease Virus with Four Knocked Out Genes Was Attenuated In Vivo and Protects Cattle from Infection.

作者信息

Chervyakova Olga, Issabek Aisha, Sultankulova Kulyaisan, Bopi Arailym, Kozhabergenov Nurlan, Omarova Zamira, Tulendibayev Ali, Aubakir Nurdos, Orynbayev Mukhit

机构信息

Research Institute for Biological Safety Problems, Gvardeiskiy 080409, Kazakhstan.

出版信息

Vaccines (Basel). 2022 Oct 12;10(10):1705. doi: 10.3390/vaccines10101705.

DOI:10.3390/vaccines10101705
PMID:36298570
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9610274/
Abstract

Vaccination with live attenuated vaccines is a key element in the prevention of lumpy skin disease. The mechanism of virus attenuation by long-term passaging in sensitive systems remains unclear. Targeted inactivation of virulence genes is the most promising way to obtain attenuated viruses. Four virulence genes in the genome of the lumpy skin disease virus (LSDV) Dermatitis nodulares/2016/Atyrau/KZ were sequentially knocked out by homologous recombination under conditions of temporary dominant selection. The recombinant LSDV Atyrau-5BJN(IL18) with a knockout of the LSDV005, LSDV008, LSDV066 and LSDV142 genes remained genetically stable for ten passages and efficiently replicated in cells of lamb testicles, saiga kidney and bovine kidney. In vivo experiments with cattle have shown that injection of the LSDV Atyrau-5BJN(IL18) at a high dose does not cause disease in animals or other deviations from the physiological norm. Immunization of cattle with the LSDV Atyrau-5BJN(IL18) induced the production of virus-neutralizing antibodies in titers of 4-5 log2. The challenge did not cause disease in immunized animals. The knockout of four virulence genes resulted in attenuation of the virulent LSDV without loss of immunogenicity. The recombinant LSDV Atyrau-5BJN(IL18) is safe for clinical use, immunogenic and protects animals from infection with the virulent LSDV.

摘要

接种减毒活疫苗是预防结节性皮肤病的关键要素。在敏感系统中通过长期传代使病毒减毒的机制仍不清楚。靶向灭活毒力基因是获得减毒病毒最有前景的方法。在临时显性选择条件下，通过同源重组依次敲除了结节性皮肤病病毒（LSDV）Dermatitis nodulares/2016/Atyrau/KZ基因组中的四个毒力基因。敲除LSDV005、LSDV008、LSDV066和LSDV142基因的重组LSDV Atyrau - 5BJN(IL18)在传代十次后仍保持遗传稳定性，并能在羔羊睾丸、高鼻羚羊肾和牛肾细胞中有效复制。对牛进行的体内实验表明，高剂量注射LSDV Atyrau - 5BJN(IL18)不会使动物发病或出现其他偏离生理标准的情况。用LSDV Atyrau - 5BJN(IL18)免疫牛可诱导产生效价为4 - 5 log2的病毒中和抗体。攻毒不会使免疫动物发病。四个毒力基因的敲除导致强毒LSDV减毒而不丧失免疫原性。重组LSDV Atyrau - 5BJN(IL18)临床使用安全、具有免疫原性，并能保护动物免受强毒LSDV感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8920/9610274/e2833f7ad0a2/vaccines-10-01705-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8920/9610274/4ee73b302816/vaccines-10-01705-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8920/9610274/bf5fd9bc3059/vaccines-10-01705-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8920/9610274/f965a0b908cd/vaccines-10-01705-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8920/9610274/e2833f7ad0a2/vaccines-10-01705-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8920/9610274/4ee73b302816/vaccines-10-01705-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8920/9610274/bf5fd9bc3059/vaccines-10-01705-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8920/9610274/f965a0b908cd/vaccines-10-01705-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8920/9610274/e2833f7ad0a2/vaccines-10-01705-g004.jpg

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