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一株针对当前非洲猪瘟流行株的细胞培养适应疫苗病毒。

A Cell Culture-Adapted Vaccine Virus against the Current African Swine Fever Virus Pandemic Strain.

机构信息

Plum Island Animal Disease Center, ARS, USDA, Greenport, New York, USA.

Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, Tennessee, USA.

出版信息

J Virol. 2021 Jun 24;95(14):e0012321. doi: 10.1128/JVI.00123-21.

DOI:10.1128/JVI.00123-21
PMID:33952643
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8315737/
Abstract

African swine fever virus (ASFV) causes a virulent, deadly infection in wild and domestic swine and is currently causing a pandemic covering a contiguous geographical area from Central and Eastern Europe to Asia. No commercial vaccines are available to prevent African swine fever (ASF), resulting in devastating economic losses to the swine industry. The most advanced vaccine candidates are live attenuated strains developed using a genetically modified virulent parental virus. Recently, we developed a vaccine candidate, ASFV-G-ΔI177L, by deleting the I177L gene from the genome of the highly virulent ASFV pandemic strain Georgia (ASFV-G). ASFV-G-ΔI177L is safe and highly efficacious in challenge studies using parental ASFV-G. Large-scale production of ASFV-G-ΔI177L has been limited because it can replicate efficiently only in primary swine macrophages. Here, we present the development of an ASFV-G-ΔI177L derivative strain, ASFV-G-ΔI177L/ΔLVR, that replicates efficiently in a stable porcine cell line. In challenge studies, ASFV-G-ΔI177L/ΔLVR maintained the same level of attenuation, immunogenic characteristics, and protective efficacy as ASFV-G-ΔI177L. ASFV-G-ΔI177L/ΔLVR is the first rationally designed ASF vaccine candidate that can be used for large-scale commercial vaccine manufacture. African swine fever is currently causing a pandemic resulting in devastating losses to the swine industry. Experimental ASF vaccines rely on the production of vaccine in primary swine macrophages, which are difficult to use for the production of a vaccine on a commercial level. Here, we report a vaccine for ASFV with a deletion in the left variable region (LVR). This deletion allows for growth in stable cell cultures while maintaining the potency and efficacy of the parental vaccine strain. This discovery will allow for the production of an ASF vaccine on a commercial scale.

摘要

非洲猪瘟病毒(ASFV)可引起野生和家养猪的致命性强毒感染,目前正在从中欧和东欧到亚洲的连续地理区域引发大流行。没有可用于预防非洲猪瘟(ASF)的商业疫苗,这导致养猪业遭受了毁灭性的经济损失。最先进的疫苗候选物是使用遗传修饰的强毒亲本病毒开发的活减毒菌株。最近,我们通过从高度致命的 ASF 大流行株格鲁吉亚(ASFV-G)的基因组中删除 I177L 基因,开发了一种疫苗候选物 ASFV-G-ΔI177L。在使用亲本 ASFV-G 的挑战研究中,ASFV-G-ΔI177L 是安全且高效的。由于其仅能在原代猪巨噬细胞中高效复制,因此大规模生产 ASFV-G-ΔI177L 受到限制。在这里,我们介绍了一种 ASFV-G-ΔI177L 衍生株 ASFV-G-ΔI177L/ΔLVR 的开发,该衍生株在稳定的猪源细胞系中高效复制。在挑战研究中,ASFV-G-ΔI177L/ΔLVR 保持与 ASFV-G-ΔI177L 相同的减毒程度、免疫原性特征和保护效力。ASFV-G-ΔI177L/ΔLVR 是第一个可用于大规模商业疫苗生产的合理设计的 ASF 疫苗候选物。非洲猪瘟目前正在引发大流行,导致养猪业遭受毁灭性损失。实验性 ASF 疫苗依赖于在原代猪巨噬细胞中生产疫苗,这对于在商业水平上生产疫苗而言具有挑战性。在这里,我们报告了一种针对 ASFV 的疫苗,该疫苗缺失了左可变区(LVR)。这种缺失允许在稳定的细胞培养物中生长,同时保持亲本疫苗株的效力和功效。这一发现将使 ASF 疫苗能够在商业规模上生产。

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J Virol. 2020 Mar 17;94(7). doi: 10.1128/JVI.02017-19.
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CRISPR-Cas9, a tool to efficiently increase the development of recombinant African swine fever viruses.CRISPR-Cas9,一种有效提高重组非洲猪瘟病毒研发效率的工具。
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Evaluation of protection induced by immunisation of domestic pigs with deletion mutant African swine fever virus BeninΔMGF by different doses and routes.评估不同剂量和途径免疫非洲猪瘟病毒 BeninΔMGF 缺失突变株对家猪的保护作用。
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Deletion of the African Swine Fever Virus Gene DP148R Does Not Reduce Virus Replication in Culture but Reduces Virus Virulence in Pigs and Induces High Levels of Protection against Challenge.删除非洲猪瘟病毒基因DP148R不会降低病毒在培养物中的复制,但会降低病毒对猪的毒力,并诱导对攻毒的高水平保护。
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