New treatment options are needed to prevent relapses following failed antibiotic therapies of Clostridium difficile infections (CDI) in humans. The concomitant therapy with an anti-C. difficile IgA containing whey protein concentrate can support the sustainable recovery of CDI patients. For 31 weeks, nine dairy cows were continuously vaccinated with several anti-C. difficile vaccines by certain routes of administration to produce anti-C. difficile IgA enriched milk. The study aimed at finding decisive differences between low responder (LR) and high responder (HR) cows (> 8.0 µg ml−1 total milk C. difficile specific IgA) concerning their immune response to vaccination on cellular and molecular biological levels. The results of total and differential cell counting (DCC) in blood and milk and the outcomes of the gene expression analysis of selected immune factors were assessed relating to the usage of two vaccine batches for injection (MucoCD-I batch A and B), marking two immunization (IM) periods, and compared to a control group (Ctr). The MucoCD-I batch A caused short-term leukopenia followed by leukocytosis in the blood of LR and HR. The total somatic cell counts in milk were not altered by the treatment. The DCC revealed that the leukocytes of the treated groups were partly impaired by the treatment. The gene expression analysis exposed cumulative and sustainable differences (p < 0.05) between LR and HR for the genes encoding for lactoferrin, CXCL8, IL1β, IL2, IL6, IL12β, IFNγ, CD4 and CD163. The regulation of the epithelial IgA cell receptor PIGR was not impaired by the IM. In contrast to the vaccination with MucoCD-I batch A, the second IM period with MucoCD-I batch B resulted in mitigation and synchronization of the treated groups’ immune responses. The inversely regulated cytokines in the blood and milk cells of the treated groups led to a variously directed, local T cell response resulting in their different production intensities of C. difficile specific IgA in milk.

中文翻译：

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接种艰难梭菌疫苗的牛体液中的免疫细胞计数和信号传递

需要新的治疗选择，以防止在人类艰难梭菌感染（CDI）的抗生素治疗失败后复发。伴随抗C疗法。含有浓缩乳清蛋白的艰难IgA可以支持CD​​I患者的可持续康复。在31周内，连续对9头奶牛接种了几种抗C疫苗。艰难疫苗通过某些给药途径产生抗C。难消化的IgA浓缩牛奶。该研究旨在发现低反应性（LR）奶牛和高反应性（HR）奶牛（> 8.0 µg ml-1总艰难梭菌特异性IgA）在细胞和分子生物学水平上对疫苗免疫反应的决定性差异。评估了与两种注射疫苗（MucoCD-1批次A和B）的使用有关的血液和牛奶中总细胞和差异细胞计数（DCC）的结果以及所选免疫因子的基因表达分析结果，两个免疫（IM）时期，并与对照组（Ctr）进行比较。MucoCD-1批次A引起短期白细胞减少症，随后在LR和HR血液中出现白细胞增多。牛奶中的总体细胞计数未因治疗而改变。DCC显示治疗组的白细胞部分受到治疗的损害。基因表达分析揭示了编码乳铁蛋白，CXCL8，IL1β，IL2，IL6，IL12β，IFNγ，CD4和CD163的基因在LR和HR之间的累积和可持续差异（p <0.05）。IM不会损害上皮IgA细胞受体PIGR的调节。与用MucoCD-1批次A进行疫苗接种相反，用MucoCD-1批次B进行的第二个IM期可减轻和同步治疗组的免疫反应。在治疗组的血液和乳细胞中逆调节的细胞因子导致不同方向的局部T细胞反应，导致它们在牛奶中的艰难梭菌特异性IgA产生强度不同。