Comparative structural and immunological analysis of outer membrane proteins and dermonecrotic toxin in Bordetella bronchiseptica canine isolate

IF 1.4 3区农林科学 Q4 IMMUNOLOGY Veterinary immunology and immunopathology Pub Date : 2024-04-20 DOI:10.1016/j.vetimm.2024.110756

Ji Young Jang , Myung Whan Oh , Chaeyeong Na , Young Bin Im , Soojin Shim , Hyoung Joon Moon , Han Sang Yoo

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Abstract

Bordetella bronchiseptica is a pathogen causing respiratory infections in mammals. With the improving understanding of companion animals’ welfare, addressing the side effects of bordetella vaccine gains importance in dogs. Studies on diverse subunit vaccines are actively pursued in humans to safely and effectively control bordetellosis. Therefore, our objective was to develop a canine bordetella vaccine inspired by human vaccine development. We evaluated the immunogenicity of the two bacterial components: the outer membrane proteins (OMPs) and the dermonecrotic toxin (DNT) from a canine isolate of B. bronchiseptica. In-silico analysis identified eight domains of DNT, and Domain 3 was selected as the most promising antigen candidate. Additionally, the OMPs were extracted and examined using SDS-PAGE and Western blot analysis. The distinct immunological characteristic of OMPs and DNT-3 were examined individually and in combination. Gene expression and cytokine production were also evaluated in DH82 cells after stimulation with those antigens. Treatment with OMPs resulted in higher level of Th1 related cytokines, while DNT-3 induced a predominant response associated with Th17 and Th2 in the cytokine production. Synergistic effects were observed exclusively on IL-23, indicating increase of a potential risk of side effects when OMPs and DNT act together. These findings provide valuable insights into the reactogenicity of conventional Bordetella vaccines. Further, the presented preclinical data in this study offer an alternative method of the development for an optimal next-generation Bordetella vaccine for companion animals and humans, replacing the acellular vaccines containing both toxin and protein components.

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犬支气管败血波氏杆菌分离株的外膜蛋白和腐皮毒素的结构和免疫学比较分析

支气管败血波氏杆菌是一种导致哺乳动物呼吸道感染的病原体。随着人们对伴侣动物福利认识的不断提高，解决狗接种博德特氏菌疫苗的副作用问题变得越来越重要。为了安全有效地控制博德特氏菌病，人类正在积极开展有关各种亚单位疫苗的研究。因此，我们的目标是受人类疫苗开发的启发，开发一种犬科博德特氏菌疫苗。我们评估了两种细菌成分的免疫原性：来自犬支气管败血波氏杆菌分离株的外膜蛋白（OMPs）和腐皮毒素（DNT）。室内分析确定了 DNT 的八个结构域，其中结构域 3 被选为最有希望的候选抗原。此外，还提取了 OMPs，并使用 SDS-PAGE 和 Western 印迹分析对其进行了检测。研究人员对 OMPs 和 DNT-3 的不同免疫特征进行了单独和组合研究。还评估了 DH82 细胞在受到这些抗原刺激后的基因表达和细胞因子产生情况。用 OMPs 处理会导致 Th1 相关细胞因子水平升高，而 DNT-3 则会诱导 Th17 和 Th2 相关细胞因子的主要反应。只在 IL-23 上观察到了协同效应，这表明当 OMPs 和 DNT 同时作用时，副作用的潜在风险会增加。这些发现为了解传统博德特氏菌疫苗的致反应性提供了宝贵的见解。此外，本研究中展示的临床前数据还为开发用于伴侣动物和人类的最佳下一代博德特氏菌疫苗提供了一种替代方法，以取代同时含有毒素和蛋白质成分的无细胞疫苗。

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来源期刊

Veterinary immunology and immunopathology 农林科学-免疫学

CiteScore

3.40

自引率

5.60%

发文量

审稿时长

70 days

期刊介绍： The journal reports basic, comparative and clinical immunology as they pertain to the animal species designated here: livestock, poultry, and fish species that are major food animals and companion animals such as cats, dogs, horses and camels, and wildlife species that act as reservoirs for food, companion or human infectious diseases, or as models for human disease. Rodent models of infectious diseases that are of importance in the animal species indicated above,when the disease requires a level of containment that is not readily available for larger animal experimentation (ABSL3), will be considered. Papers on rabbits, lizards, guinea pigs, badgers, armadillos, elephants, antelope, and buffalo will be reviewed if the research advances our fundamental understanding of immunology, or if they act as a reservoir of infectious disease for the primary animal species designated above, or for humans. Manuscripts employing other species will be reviewed if justified as fitting into the categories above. The following topics are appropriate: biology of cells and mechanisms of the immune system, immunochemistry, immunodeficiencies, immunodiagnosis, immunogenetics, immunopathology, immunology of infectious disease and tumors, immunoprophylaxis including vaccine development and delivery, immunological aspects of pregnancy including passive immunity, autoimmuity, neuroimmunology, and transplanatation immunology. Manuscripts that describe new genes and development of tools such as monoclonal antibodies are also of interest when part of a larger biological study. Studies employing extracts or constituents (plant extracts, feed additives or microbiome) must be sufficiently defined to be reproduced in other laboratories and also provide evidence for possible mechanisms and not simply show an effect on the immune system.