Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria, 3800, Australia.
Sci Rep. 2017 Jun 16;7(1):3665. doi: 10.1038/s41598-017-03982-5.
The increased incidence of antibiotic resistant 'superbugs' has amplified the use of broad spectrum antibiotics worldwide. An unintended consequence of antimicrobial treatment is disruption of the gastrointestinal microbiota, resulting in susceptibility to opportunistic pathogens, such as Clostridium difficile. Paradoxically, treatment of C. difficile infections (CDI) also involves antibiotic use, leaving patients susceptible to re-infection. This serious health threat has led to an urgent call for the development of new therapeutics to reduce or replace the use of antibiotics to treat bacterial infections. To address this need, we have developed colostrum-derived antibodies for the prevention and treatment of CDI. Pregnant cows were immunised to generate hyperimmune bovine colostrum (HBC) containing antibodies that target essential C. difficile virulence components, specifically, spores, vegetative cells and toxin B (TcdB). Mouse infection and relapse models were used to compare the capacity of HBC to prevent or treat primary CDI as well as prevent recurrence. Administration of TcdB-specific colostrum alone, or in combination with spore or vegetative cell-targeted colostrum, prevents and treats C. difficile disease in mice and reduces disease recurrence by 67%. C. difficile-specific colostrum should be re-considered as an immunotherapeutic for the prevention or treatment of primary or recurrent CDI.
广谱抗生素的广泛使用加剧了抗生素耐药“超级细菌”的发生。抗菌治疗的一个意外后果是破坏了胃肠道微生物群，导致易患机会性病原体，如艰难梭菌。具有讽刺意味的是，艰难梭菌感染（CDI）的治疗也涉及抗生素的使用，使患者容易再次感染。这一严重的健康威胁促使人们迫切需要开发新的疗法来减少或替代抗生素治疗细菌感染。为了满足这一需求，我们开发了源自牛初乳的抗体，用于预防和治疗 CDI。对怀孕的奶牛进行免疫接种，以产生含有针对艰难梭菌必需毒力成分的抗体的高免疫牛初乳（HBC），特别是孢子、营养细胞和毒素 B（TcdB）。我们使用小鼠感染和复发模型来比较 HBC 预防或治疗原发性 CDI 以及预防复发的能力。单独给予 TcdB 特异性牛初乳，或与靶向孢子或营养细胞的牛初乳联合使用，可预防和治疗小鼠的艰难梭菌疾病，并将疾病复发减少 67%。艰难梭菌特异性牛初乳应重新考虑作为预防或治疗原发性或复发性 CDI 的免疫疗法。
