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水禽呼肠孤病毒感染活疫苗的研制。

Development of a live attenuated vaccine against Muscovy duck reovirus infection.

机构信息

Institute of Animal Husbandry and Veterinary Medicine, Fujian Academy of Agricultural Sciences, Fuzhou 350013, China; Fujian Animal Diseases Control Technology Development Center, Fuzhou 350013, China.

Institute of Animal Husbandry and Veterinary Medicine, Fujian Academy of Agricultural Sciences, Fuzhou 350013, China; Fujian Animal Diseases Control Technology Development Center, Fuzhou 350013, China.

出版信息

Vaccine. 2018 Dec 18;36(52):8001-8007. doi: 10.1016/j.vaccine.2018.10.102. Epub 2018 Nov 9.

Abstract

The Muscovy duck reovirus (MDRV) is a highly pathogenic virus that causes substantial economic losses in the Muscovy duck industry. While MDRV poses a significant threat to Muscovy ducklings, no vaccine candidates are available to date to alleviate MDRV infection throughout the world. The present study presents efforts toward establishing an attenuated vaccine for MDRV. For this purpose, a live attenuated vaccine strain named CA was obtained via alternate propagation of the MDRV isolate MW9710 in both Muscovy duck embryo fibroblasts (MDEFs) and chicken embryo fibroblasts (CEFs) for 90 passages. The CA strain achieved an adaptive growth capacity in CEFs with a viral titer that ranged between 10-10 TCID/100 μL and lost its pathogenicity in 1-day-old Muscovy ducklings. Compared to the parent strain MW9710, the CA strain has 42 scattered amino acid substitutions, most of which are located in the λB, λC, μB, σB, and σC protein. The CA strain maintained its attenuation and showed no gene mutation or virulence reversion after back propagation into 1-day-old ducklings for five rounds. The minimum protective dose was calculated to be 300 TCID of the CA strain. Furthermore, a single dose of CA vaccine protected immunized ducklings against lethal challenge by the virulent MDRV strain MW9710 and significantly decreased viral loads. In summary, the CA strain exhibited striking genetic stability, excellent safety, and effective immunogenicity. This CA strain of MDRV is a promising vaccine candidate for the prevention and control of MDRV infection.

摘要

番鸭呼肠孤病毒(Muscovy duck reovirus,MDRV)是一种高致病性病毒,给番鸭养殖业造成了巨大的经济损失。虽然 MDRV 对番鸭雏鸭构成了重大威胁,但目前全球尚无可用的疫苗候选物来缓解 MDRV 感染。本研究旨在开发 MDRV 的减毒活疫苗。为此,通过在番鸭胚胎成纤维细胞(Muscovy duck embryo fibroblasts,MDEF)和鸡胚成纤维细胞(chicken embryo fibroblasts,CEF)中交替传代 MDRV 分离株 MW9710 90 代,获得了一株名为 CA 的减毒活疫苗株。CA 株在 CEF 中获得了适应性生长能力,病毒滴度在 10-10 TCID/100 μL 之间,在 1 日龄番鸭雏鸭中丧失了致病性。与亲本株 MW9710 相比,CA 株有 42 个分散的氨基酸取代,其中大多数位于 λB、λC、μB、σB 和 σC 蛋白中。CA 株保持了其减毒特性,在连续传代至 1 日龄雏鸭 5 代后没有发生基因突变或毒力回复。最小保护剂量计算为 300 TCID 的 CA 株。此外,单次剂量的 CA 疫苗可保护免疫雏鸭免受强毒 MDRV 株 MW9710 的致死性攻击,并显著降低病毒载量。总之,CA 株表现出显著的遗传稳定性、优异的安全性和有效的免疫原性。该 CA 株番鸭呼肠孤病毒是预防和控制 MDRV 感染的有前途的疫苗候选物。

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