Protective Efficacy of Decreasing Antigen Doses of a Chlamydia abortus Subcellular Vaccine Against Ovine Enzootic Abortion in a Pregnant Sheep Challenge Model.

IF 5.2 3区 医学 Q1 IMMUNOLOGY Vaccines Pub Date : 2025-01-18 DOI:10.3390/vaccines13010089
Morag Livingstone, Kevin Aitchison, Javier Palarea-Albaladejo, Francesco Ciampi, Clare Underwood, Antonia Paladino, Francesca Chianini, Gary Entrican, Sean Ranjan Wattegedera, David Longbottom
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Abstract

Background/objective: Chlamydia abortus, the cause of ovine enzootic abortion, is a zoonotic bacterial pathogen and one of the most infectious causes of foetal death in sheep worldwide. Although the disease can be controlled using commercial inactivated and live whole-organism vaccines, there are issues with both, particularly concerning efficacy and safety. Recently, we have described the development of a new COMC (chlamydial outer membrane complex) vaccine based on a detergent-extracted outer membrane protein preparation of the pathogen, which can be delivered in a single inoculation and is both efficacious and safe.

Methods: In this study, we have evaluated the COMC vaccine further in a dose-response titration of the chlamydial antigen content of the vaccine (from 20 to 2.5 µg in seven experimental groups) using an established pregnant sheep challenge model.

Results: No obvious dose-response relationship was observed across the groups, with a single abortion event occurring in four of the groups and three in the lowest dose group (2.5 µg). No abortions occurred in the 15 and 10 µg groups. The abortion rates (0-14%) were significantly below that of the challenge control group (33%). A similar reduction in bacterial shedding of infectious organisms following parturition was observed in the vaccinated groups compared to the challenge control group, which is important in terms of reducing potential transmission to naive animals.

Conclusions: The results show that a dose of 10 µg antigen in the vaccine will be optimal in terms of maximising efficacy, reducing shedding at parturition, and ensuring it is cost-effective to produce for commercial manufacture.

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降低流产衣原体亚细胞疫苗抗原剂量对妊娠绵羊地方性流产的保护作用
背景/目的:羊先天性流产衣原体是一种人畜共患细菌性病原体,是绵羊胎儿死亡的主要原因之一。虽然这种疾病可以使用商业灭活疫苗和活的全生物体疫苗来控制,但这两种疫苗都存在问题,特别是在有效性和安全性方面。最近,我们描述了一种新的COMC(衣原体外膜复合物)疫苗的开发,该疫苗基于病原体的洗涤剂提取外膜蛋白制备,可以单次接种,既有效又安全。方法:在本研究中,我们利用已建立的妊娠绵羊攻毒模型,对COMC疫苗进行了剂量反应滴定,对疫苗的衣原体抗原含量(7个实验组从20µg到2.5µg)进行了进一步评估。结果:各组间无明显的剂量-反应关系,4组发生单次流产,最低剂量组(2.5µg)发生3次流产。15和10µg组未发生流产。流产率(0 ~ 14%)明显低于攻毒对照组(33%)。与挑战对照组相比,在分娩后接种疫苗的组中观察到传染性生物体的细菌脱落也有类似的减少,这对于减少潜在的向幼稚动物传播是重要的。结论:从疫苗的最大功效、减少分娩时的脱落和确保商业化生产的成本效益来看,10µg抗原的疫苗剂量是最佳的。
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来源期刊
Vaccines
Vaccines Pharmacology, Toxicology and Pharmaceutics-Pharmacology
CiteScore
8.90
自引率
16.70%
发文量
1853
审稿时长
18.06 days
期刊介绍: Vaccines (ISSN 2076-393X) is an international, peer-reviewed open access journal focused on laboratory and clinical vaccine research, utilization and immunization. Vaccines publishes high quality reviews, regular research papers, communications and case reports.
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