Yan Weiwei, Shin Kang-Soon, Wang Shih-Jon, Xiang Hua, Divers Thomas, McDonough Sean, Bowman James, Rowlands Anne, Akey Bruce, Mohamed Hussni, Chang Yung-Fu
Animal Health Diagnostic Center, Departments of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
J Vet Sci. 2014;15(2):249-58. doi: 10.4142/jvs.2014.15.2.249. Epub 2013 Oct 18.
Clostridium (C.) difficile is a common cause of nosocomial diarrhea in horses. Vancomycin and metronidazole have been used as standard treatments but are only moderately effective, which highlights the need for a novel alternative therapy. In the current study, we prepared antiserum of equine origin against both C. difficile toxins A and B as well as whole-cell bacteria. The toxin-neutralizing activities of the antibodies were evaluated in vitro and the prophylactic effects of in vivo passive immunotherapy were demonstrated using a conventional mouse model. The data demonstrated that immunized horses generated antibodies against both toxins A and B that possessed toxin-neutralizing activity. Additionally, mice treated with the antiserum lost less weight without any sign of illness and regained weight back to a normal range more rapidly compared to the control group when challenged orally with 10(7) C. difficile spores 1 day after serum injection. These results indicate that intravenous delivery of hyperimmune serum can protect animals from C. difficile challenge in a dose-dependent manner. Hence, immunotherapy may be a promising prophylactic strategy for preventing C. difficile infection in horses.
艰难梭菌是马匹医院获得性腹泻的常见病因。万古霉素和甲硝唑一直作为标准治疗药物,但效果仅为中等,这凸显了对新型替代疗法的需求。在本研究中,我们制备了针对艰难梭菌毒素A和毒素B以及全菌的马源抗血清。在体外评估了抗体的毒素中和活性,并使用传统小鼠模型证明了体内被动免疫疗法的预防效果。数据表明,免疫后的马匹产生了针对毒素A和毒素B的具有毒素中和活性的抗体。此外,与对照组相比,在注射血清1天后经口用10(7)个艰难梭菌孢子攻击时,用抗血清治疗的小鼠体重减轻较少,没有任何疾病迹象,并且体重恢复到正常范围的速度更快。这些结果表明,静脉注射超免疫血清可以以剂量依赖的方式保护动物免受艰难梭菌的攻击。因此,免疫疗法可能是预防马匹艰难梭菌感染的一种有前景的预防策略。