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基于 IgY 的治疗方法的开发,以控制奶牛犊牛的牛冠状病毒腹泻。

Development of an IgY-Based Treatment to Control Bovine Coronavirus Diarrhea in Dairy Calves.

机构信息

INCUINTA, Virology Institute and Technology Innovations, National Institute of Agricultural Technology, Buenos Aires 1686, Argentina.

CONICET, Buenos Aires C1425FQB, Argentina.

出版信息

Viruses. 2023 Mar 9;15(3):708. doi: 10.3390/v15030708.

Abstract

Bovine Coronavirus (BCoV) is a major pathogen associated with neonatal calf diarrhea. Standard practice dictates that to prevent BCoV diarrhea, dams should be immunized in the last stage of pregnancy to increase BCoV-specific antibody (Ab) titers in serum and colostrum. For the prevention to be effective, calves need to suck maternal colostrum within the first six to twelve hours of life before gut closure to ensure a good level of passive immunity. The high rate of maternal Ab transfer failure resulting from this process posed the need to develop alternative local passive immunity strategies to strengthen the prevention and treatment of BCoV diarrhea. Immunoglobulin Y technology represents a promising tool to address this gap. In this study, 200 laying hens were immunized with BCoV to obtain spray-dried egg powder enriched in specific IgY Abs to BCoV on a large production scale. To ensure batch-to-batch product consistency, a potency assay was statistically validated. With a sample size of 241, the BCoV-specific IgY ELISA showed a sensitivity and specificity of 97.7% and 98.2%, respectively. ELISA IgY Abs to BCoV correlated with virus-neutralizing Ab titers (Pearson correlation, R = 0.92, < 0.001). Most importantly, a pilot efficacy study in newborn calves showed a significant delay and shorter duration of BCoV-associated diarrhea and shedding in IgY-treated colostrum-deprived calves. Calves were treated with milk supplemented with egg powder (final IgY Ab titer to BCoV ELISA = 512; VN = 32) for 14 days as a passive treatment before a challenge with BCoV and were compared to calves fed milk with no supplementation. This is the first study with proof of efficacy of a product based on egg powder manufactured at a scale that successfully prevents BCoV-associated neonatal calf diarrhea.

摘要

牛冠状病毒 (BCoV) 是与新生犊牛腹泻相关的主要病原体。标准做法规定,为了预防 BCoV 腹泻,应在妊娠后期对母畜进行免疫,以提高血清和初乳中的 BCoV 特异性抗体 (Ab) 滴度。为了使预防有效,犊牛需要在肠道关闭前的生命最初六到十二个小时内吮吸母畜初乳,以确保获得良好的被动免疫力水平。由于这个过程,母畜 Ab 转移失败率很高,因此需要开发替代的局部被动免疫策略来加强对 BCoV 腹泻的预防和治疗。免疫球蛋白 Y 技术代表了一种有前途的工具来解决这一差距。在这项研究中,200 只产蛋母鸡用 BCoV 免疫,以大规模生产富含针对 BCoV 的特异性 IgY Ab 的喷雾干燥蛋粉。为了确保批间产品一致性,进行了效力测定的统计验证。使用 241 个样本,针对 BCoV 的 IgY ELISA 显示出 97.7%和 98.2%的灵敏度和特异性。ELISA IgY Ab 与中和 Ab 滴度相关(Pearson 相关,R = 0.92,<0.001)。最重要的是,在新生犊牛中的一项初步疗效研究表明,IgY 处理的缺乏初乳的犊牛中,与 BCoV 相关的腹泻和脱落的发生时间明显延迟且持续时间更短。犊牛在接受 BCoV 挑战前接受了 14 天补充有蛋粉(最终 IgY Ab 对 BCoV ELISA 的滴度 = 512;VN = 32)的牛奶的被动治疗,并与未补充的犊牛进行了比较。这是第一项证明基于在成功预防与 BCoV 相关的新生犊牛腹泻的规模下生产的蛋粉制造的产品具有疗效的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57be/10059803/2caea0d3dc6c/viruses-15-00708-g001.jpg

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