A Novel Chimeric Fiber-C4/D11 Subunit Vaccine Induces Cross-Neutralizing Antibodies and Provides Better Protection Against Fowl Adenovirus (FAdV) Type 4 and Type 11 Than the Fiber-D11/C4 Subunit Vaccine.

IF 2.3 2区 农林科学 Q2 VETERINARY SCIENCES
Xiangqin Wang, Kuan Zhao, Baishi Lei, Wenming Jiang, Yanliang Qiao, Wanzhe Yuan
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Abstract

The widespread prevalence of different serotypes of fowl adenoviruses (FAdVs) has led to diverse vaccine demands, especially for subunit vaccines targeting FAdV-4 and FAdV-11, which cause hydropericardium-hepatitis syndrome (HHS) and inclusion body hepatitis (IBH), respectively. Although the Fiber protein is known to elicit robust immune protection, further exploration is needed to enhance the production of cross-neutralizing antibodies. This study utilized structural prediction and homology modeling techniques, employing domain-swapping strategy to integrate neutralizing epitope-containing amino acid sequences (274-451aa and 364-543aa) into the shaft domain of the Fiber protein. Two novel chimeric proteins were recombinantly expressed and developed into subunit vaccines: Fiber-C4/D11 and Fiber-D11/C4. Immunogenicity assessments revealed that the Fiber-C4/D11 vaccine group rapidly induced an antibody response against FAdV-11 within 7 days post-vaccination. By 28 days post-vaccination (dpv), the Fiber-C4/D11 vaccine group exhibited significantly higher levels of cross-neutralizing antibodies compared to the Fiber-D11/C4 group (p < 0.05). Challenge experiments demonstrated that both vaccines effectively alleviated clinical symptoms and prevented mortality in SPF chickens. Compared to Fiber-D11/C4, Fiber-C4/D11 significantly reduced body weight loss, liver lesions, viral titers in tissues, and viral shedding. Notably, no cross-neutralizing antibodies were detected following FAdV-4 or FAdV-11 infection, indicating a lack of natural cross-protection between the two serotypes. The chimeric vaccine addressed this gap, offering a promising multivalent approach to mitigate FAdV infections and advancing fowl adenoviral subunit vaccine strategies.

新型嵌合纤维-C4/D11亚单位疫苗诱导交叉中和抗体,对禽腺病毒(FAdV) 4型和11型的保护作用优于纤维-D11/C4亚单位疫苗。
不同血清型禽腺病毒(FAdVs)的广泛流行导致了不同的疫苗需求,特别是针对fadv4和fadv11的亚单位疫苗,这两种病毒分别引起心包膜-肝炎综合征(HHS)和包涵体肝炎(IBH)。虽然已知纤维蛋白可引起强大的免疫保护,但需要进一步探索以增强交叉中和抗体的产生。本研究利用结构预测和同源性建模技术,采用结构域交换策略将含有表位的中和氨基酸序列(274-451aa和364-543aa)整合到Fiber蛋白的轴结构域。重组表达了两种新的嵌合蛋白:Fiber-C4/D11和Fiber-D11/C4。免疫原性评估显示,纤维- c4 /D11疫苗组在接种后7天内迅速诱导了针对FAdV-11的抗体应答。接种后28天,纤维-C4/D11疫苗组的交叉中和抗体水平显著高于纤维-D11/C4疫苗组(p < 0.05)。挑战实验表明,这两种疫苗都能有效缓解SPF鸡的临床症状并防止死亡。与纤维-D11/C4相比,纤维-C4/D11显著减轻了体重减轻、肝脏病变、组织病毒滴度和病毒脱落。值得注意的是,FAdV-4或FAdV-11感染后未检测到交叉中和抗体,表明两种血清型之间缺乏自然交叉保护。嵌合疫苗填补了这一空白,提供了一种有希望的多价方法来减轻FAdV感染,并推进了家禽腺病毒亚单位疫苗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Veterinary Sciences
Veterinary Sciences VETERINARY SCIENCES-
CiteScore
2.90
自引率
8.30%
发文量
612
审稿时长
6 weeks
期刊介绍: Veterinary Sciences is an international and interdisciplinary scholarly open access journal. It publishes original that are relevant to any field of veterinary sciences, including prevention, diagnosis and treatment of disease, disorder and injury in animals. This journal covers almost all topics related to animal health and veterinary medicine. Research fields of interest include but are not limited to: anaesthesiology anatomy bacteriology biochemistry cardiology dentistry dermatology embryology endocrinology epidemiology genetics histology immunology microbiology molecular biology mycology neurobiology oncology ophthalmology parasitology pathology pharmacology physiology radiology surgery theriogenology toxicology virology.
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