Department of Infectious Disease, College of Veterinary Medicine, Seoul National University, Seoul, South Korea; Green Cross Veterinary Products Co., Ltd, Yongin, South Korea.
Department of Infectious Disease, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
Vet Immunol Immunopathol. 2024 Jun;272:110756. doi: 10.1016/j.vetimm.2024.110756. Epub 2024 Apr 20.
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.
支气管败血波氏杆菌是一种引起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提高，狗用博德特氏菌疫苗的副作用问题变得越来越重要。目前，人们正在积极研究各种亚单位疫苗，以安全有效地控制波氏杆菌病。因此，我们的目标是借鉴人类疫苗开发的经验，开发一种犬用博德特氏菌疫苗。我们评估了两种细菌成分的免疫原性：从犬源支气管败血波氏杆菌分离株中提取的外膜蛋白（OMPs）和坏死毒素（DNT）。通过计算机分析，我们确定了 DNT 的 8 个结构域，其中第 3 结构域被选为最有前途的抗原候选物。此外，我们还使用 SDS-PAGE 和 Western blot 分析提取和检查了 OMPs。单独和联合使用 OMPs 和 DNT-3 检测了它们的独特免疫特性。还评估了这些抗原刺激 DH82 细胞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 诱导的细胞因子产生主要与 Th17 和 Th2 相关。仅在 IL-23 上观察到协同作用，这表明 OMPs 和 DNT 同时作用时可能会增加副作用的风险。这些发现为传统博德特氏菌疫苗的反应原性提供了有价值的见解。此外，本研究中的临床前数据提供了一种替代方法，用于开发伴侣动物和人类的下一代博德特氏菌最佳疫苗，替代含有毒素和蛋白成分的非细胞疫苗。
