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减毒副鸡禽杆菌菌株作为传染性鼻炎活疫苗候选株的研制与评价

Development and evaluation of an attenuated Avibacterium paragallinarum strain as a live vaccine candidate for infectious coryza.

作者信息

Guo Mengjiao, Wang Haonan, Liu Donghui, Bo Zongyi, Zhang Chengcheng, Wu Yantao, Zhang Xiaorong

机构信息

Jiangsu Co-Innovation Center for Prevention of Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, China.

Joint International Research Laboratory of Agriculture & Agri-Product Safety, Yangzhou University (JIRLAAPS), Yangzhou, 225009, China.

出版信息

Vet Res. 2025 Jun 9;56(1):115. doi: 10.1186/s13567-025-01546-4.

DOI:10.1186/s13567-025-01546-4
PMID:40490807
Abstract

Avibacterium paragallinarum (Av. paragallinarum), the causative agent of infectious coryza, is a significant pathogen responsible for substantial economic losses in the poultry industry. Current preventive strategies rely primarily on inactivated vaccines, which have limitations such as vaccine failure and limited cross-protection between serotypes. This study aimed to develop an attenuated strain of Av. paragallinarum as a potential live vaccine candidate. Using the Tn5-Kan transposon, we constructed a transposon mutant library and identified a mutant strain, designated 2019/HB64-40, which harbored a disrupted ksgA gene encoding a critical enzyme involved in ribosomal RNA methylation. Compared with the wild-type strain, the 2019/HB64-40 strain presented significantly reduced biofilm formation, lower hemagglutination titres, and impaired growth. Pathogenicity assessments in chickens demonstrated that the mutant strain displayed significantly attenuated virulence, characterized by fewer clinical symptoms and reduced bacterial shedding. Furthermore, following challenge, all unimmunized chickens presented severe clinical signs of infectious coryza at 2 dpi, with symptoms beginning to ameliorate by 5 dpi, culminating in a mean clinical sign score of 2.1. In contrast, only one chicken (1/10) in the immunized group displayed mild facial swelling and nasal discharge, with a mean clinical sign score of 0.1. The immunized group receiving the 2019/HB64-40 strain demonstrated 90% immunoprotection, highlighting the potential of this attenuated strain as a live vaccine candidate. While cross-serotype protection was not evaluated, the results suggest effective homologous protection and colonization capacity, underscoring its promising application in the prevention and treatment of infectious coryza.

摘要

副鸡禽杆菌(Av. paragallinarum)是传染性鼻炎的病原体,是导致家禽业重大经济损失的重要病原菌。目前的预防策略主要依赖于灭活疫苗,这些疫苗存在疫苗失效和血清型间交叉保护有限等局限性。本研究旨在开发一种副鸡禽杆菌减毒株作为潜在的活疫苗候选株。我们使用Tn5-Kan转座子构建了一个转座子突变体文库,并鉴定出一个突变株,命名为2019/HB64-40,该菌株的ksgA基因被破坏,该基因编码一种参与核糖体RNA甲基化的关键酶。与野生型菌株相比,2019/HB64-40菌株的生物膜形成显著减少,血凝滴度降低,生长受损。在鸡身上进行的致病性评估表明,该突变株的毒力显著减弱,表现为临床症状较少和细菌排泄减少。此外,攻毒后,所有未免疫的鸡在感染后第2天出现传染性鼻炎的严重临床症状,症状在感染后第5天开始缓解,最终平均临床症状评分为2.1。相比之下,免疫组中只有一只鸡(1/10)出现轻度面部肿胀和鼻液,平均临床症状评分为0.1。接受2019/HB64-40菌株免疫组表现出90%的免疫保护率,突出了该减毒株作为活疫苗候选株的潜力。虽然未评估交叉血清型保护,但结果表明其具有有效的同源保护和定植能力,强调了其在传染性鼻炎预防和治疗中的应用前景。

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