Chair of Food and Bioprocess Engineering, Technical University of Munich, 85354 Freising, Germany.
ZIEL Institute for Food & Health, Technical University of Munich, 85354 Freising, Germany.
Toxins (Basel). 2019 Feb 6;11(2):98. doi: 10.3390/toxins11020098.
Toxin-induced infection (CDI) is a major disease characterized by severe diarrhea and high morbidity rates. The aim with this study was to develop an alternative drug for the treatment of CDI. Cows were repeatedly immunized to establish specific immunoglobulin G and A titers against toxins A (TcdA) and B (TcdB) and against cells in mature milk or colostrum. The effect of three different concentrations of anti- whey protein isolates (anti-CD-WPI) and the standard of care antibiotic vancomycin were investigated in an animal model of CD infected hamsters (6 groups, with 10 hamsters each). WPI obtained from the milk of exactly the same cows pre-immunization and a vehicle group served as negative controls. The survival of hamsters receiving anti-CD-WPI was 50, 80 and 100% compared to 10 and 0% for the control groups, respectively. Vancomycin suppressed the growth of and thus protected the hamsters at the time of administration, but 90% of these hamsters nevertheless died shortly after discontinuation of treatment. In contrast, the surviving hamsters of the anti-CD-WPI groups survived the entire study period, although they were treated for only 75 h. The specific antibodies not only inactivated the toxins for initial suppression of CDI, but also provoked the inhibition of growth after discontinuation, thus preventing recurrence. Oral administration of anti-CD-WPI is a functional therapy of CDI in infected hamsters for both primary treatment and prevention of recurrence. Thus, anti-CD-WPI could address the urgent unmet medical need for treating and preventing recurrent CDI in humans.
产肠毒素性感染（CDI）是一种以严重腹泻和高发病率为特征的主要疾病。本研究的目的是开发一种治疗 CDI 的替代药物。通过反复免疫奶牛，建立针对毒素 A（TcdA）和 B（TcdB）以及成熟乳或初乳中 细胞的特异性免疫球蛋白 G 和 A 滴度。在感染 CD 的仓鼠动物模型中（6 组，每组 10 只），研究了三种不同浓度的抗乳清蛋白分离物（抗-CD-WPI）和标准护理抗生素万古霉素的作用。来自预免疫奶牛乳汁的 WPI 以及载体组作为阴性对照。接受抗-CD-WPI 的仓鼠的存活率分别为 50%、80%和 100%，而对照组的存活率分别为 10%和 0%。万古霉素抑制了 的生长，从而在给药时保护了仓鼠，但 90%的仓鼠在治疗停止后不久仍死亡。相比之下，抗-CD-WPI 组的存活仓鼠在整个研究期间存活下来，尽管它们仅接受了 75 小时的治疗。特异性抗体不仅使毒素失活以抑制 CDI 的初始发作，而且在停药后还引发了 生长的抑制，从而防止了复发。口服抗-CD-WPI 是感染仓鼠 CDI 的功能性治疗方法，可用于初次治疗和预防复发。因此，抗-CD-WPI 可以解决治疗和预防人类复发性 CDI 的迫切未满足的医疗需求。
