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钩端螺旋体特异性免疫球蛋白 Y(IgY)可对感染的仓鼠提供保护。

Leptospira-specific immunoglobulin Y (IgY) is protective in infected hamsters.

机构信息

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun 130062, China.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun 130062, China; State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130062, China.

出版信息

Vaccine. 2024 May 10;42(13):3220-3229. doi: 10.1016/j.vaccine.2024.04.010. Epub 2024 Apr 18.

DOI:10.1016/j.vaccine.2024.04.010
PMID:38641497
Abstract

Leptospirosis, a globally significant zoonotic disease caused by pathogenic Leptospira, continues to threaten the health and public safety of both humans and animals. Current clinical treatment of leptospirosis mainly relies on antibiotics but their efficacy in severe cases is controversial. Passive immunization has a protective effect in the treatment of infectious diseases. In addition, chicken egg yolk antibody (IgY) has gained increasing attention as a safe passive immunization agent. This study aimed to investigate whether hens produce specific IgY after immunization with inactivated Leptospira and the protective effect of specific IgY against leptospirosis. First, it was demonstrated that specific IgY could be extracted from the eggs of hens vaccinated with inactivated Leptospira and that specific IgY can specifically recognize and bind homotypic Leptospira with a high titre, as shown by MAT and ELISA. Next, we tested the therapeutic effects of IgY in early and late leptospirosis using a hamster model. The results showed that early specific IgY treatment increased the survival rate of hamsters to 100%, alleviated pathological damage to the liver, kidney, and lung, reduced leptospiral burden, and restored haematological indices as well as functional indicators of the liver and kidney. The therapeutic effect of early specific IgY was comparable to that of doxycycline. Late IgY treatment also enhanced the survival rate of hamsters and improved the symptoms of leptospirosis similar to early IgY treatment. However, the therapeutic effect of late IgY treatment was better when combined with doxycycline. Furthermore, no Leptospira colonization was observed in the kidneys, livers, or lungs of the surviving hamsters treated with specific IgY. Mechanistically, IgY was found to inhibit the growth and adhesion to cells of Leptospira. In conclusion, passive immunotherapy with specific IgY can be considered an effective treatment for leptospirosis, and may replace antibiotics regarding its therapeutic effects.

摘要

钩端螺旋体病是一种由致病性钩端螺旋体引起的全球性重要动物源性传染病,继续威胁着人类和动物的健康和公共安全。目前,钩端螺旋体病的临床治疗主要依赖于抗生素,但在严重病例中的疗效存在争议。被动免疫在传染病的治疗中具有保护作用。此外,鸡卵黄抗体(IgY)作为一种安全的被动免疫制剂越来越受到关注。本研究旨在探讨免疫灭活钩端螺旋体后母鸡是否能产生特异性 IgY,以及特异性 IgY 对钩端螺旋体病的保护作用。首先,研究表明,从接种灭活钩端螺旋体的母鸡的鸡蛋中可以提取特异性 IgY,并且特异性 IgY 可以特异地识别和结合同型钩端螺旋体,具有高滴度,如 MAT 和 ELISA 所示。接下来,我们使用仓鼠模型测试了 IgY 在早期和晚期钩端螺旋体病中的治疗效果。结果表明,早期特异性 IgY 治疗可使仓鼠的存活率提高到 100%,减轻肝、肾和肺的病理损伤,降低钩端螺旋体负荷,并恢复血液学指标以及肝、肾功能的功能指标。早期特异性 IgY 的治疗效果可与强力霉素相媲美。晚期 IgY 治疗也能提高仓鼠的存活率,并改善类似于早期 IgY 治疗的钩端螺旋体病症状。然而,晚期 IgY 治疗与强力霉素联合使用时,治疗效果更好。此外,用特异性 IgY 治疗的幸存仓鼠的肾脏、肝脏或肺部未观察到钩端螺旋体定植。从机制上讲,IgY 被发现能抑制钩端螺旋体的生长和黏附细胞。综上所述,特异性 IgY 的被动免疫疗法可被视为钩端螺旋体病的一种有效治疗方法,其治疗效果可能取代抗生素。

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