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从马中快速、高通量分离单克隆抗体的利用 - 基因偏向性。

Exploiting -Gene Bias for Rapid, High-Throughput Monoclonal Antibody Isolation from Horses.

机构信息

National Institute for Communicable Diseases, Johannesburg 2131, South Africa.

出版信息

Viruses. 2022 Sep 30;14(10):2172. doi: 10.3390/v14102172.

DOI:10.3390/v14102172
PMID:36298728
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9609571/
Abstract

Horses and humans share a close relationship that includes both species' viromes. Many emerging infectious diseases can be transmitted between horses and humans and can exhibit mortality rates as high as 90% in both populations. Antibody biologics represents an emerging field of rapidly discoverable and potent antiviral therapeutics. These biologics can be used to provide passive immunity, as well as blueprints for the rational design of novel active vaccine antigens. Here, we exploit the limited diversity of immunoglobulin variable genes used by horses to develop a rapid, high-throughput monoclonal antibody discovery pipeline. The antibodies isolated from two horses in this study were developed with near exclusivity from a few highly related germline genes within a single IgHV and IgλV gene family and could be recovered for cloning with just three primer pairs. This variable gene pairing was compatible with both horse and human immunoglobulin G isotypes, confirming the suitability of an equine antibody discovery pipeline for developing novel therapeutics to meet the One Health approach to infectious diseases.

摘要

马和人类有着密切的关系,包括两种物种的病毒组。许多新发传染病可以在马和人类之间传播,在这两种人群中的死亡率高达 90%。抗体生物制剂代表了一个新兴的领域,能够快速发现和开发强效抗病毒治疗药物。这些生物制剂可用于提供被动免疫,以及设计新型主动疫苗抗原的蓝图。在这里,我们利用马所使用的免疫球蛋白可变基因的有限多样性,开发了一种快速、高通量的单克隆抗体发现管道。从这两匹马中分离出的抗体主要来自于同一个 IgHV 和 IgλV 基因家族的少数几个高度相关的胚系基因,仅用三对引物就可以回收进行克隆。这种可变基因配对与马和人免疫球蛋白 G 同种型兼容,证实了马抗体发现管道适合开发新的治疗方法,以满足针对传染病的“同一健康”方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54dc/9609571/d077319836c8/viruses-14-02172-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54dc/9609571/ff0207f31d3e/viruses-14-02172-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54dc/9609571/e2d6943e299d/viruses-14-02172-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54dc/9609571/d7edba0bcc1f/viruses-14-02172-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54dc/9609571/7685d650218c/viruses-14-02172-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54dc/9609571/d077319836c8/viruses-14-02172-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54dc/9609571/ff0207f31d3e/viruses-14-02172-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54dc/9609571/e2d6943e299d/viruses-14-02172-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54dc/9609571/d7edba0bcc1f/viruses-14-02172-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54dc/9609571/7685d650218c/viruses-14-02172-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54dc/9609571/d077319836c8/viruses-14-02172-g005.jpg

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Snake Envenomation.蛇咬伤。
N Engl J Med. 2022 Jan 6;386(1):68-78. doi: 10.1056/NEJMra2105228.
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The origins and spread of domestic horses from the Western Eurasian steppes.家马起源于并扩散自欧亚大陆西部的草原。
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Bovine Coronavirus and the Associated Diseases.牛冠状病毒及相关疾病
Front Vet Sci. 2021 Mar 31;8:643220. doi: 10.3389/fvets.2021.643220. eCollection 2021.
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Epidemiology and Clinical Presentation of West Nile Virus Infection in Horses in South Africa, 2016-2017.2016 - 2017年南非马匹西尼罗河病毒感染的流行病学与临床表现
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