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在自然接触金黄色葡萄球菌之前,用葡萄球菌免疫逃避蛋白对年轻小母牛进行免疫接种,可在血清和乳汁中诱导体液免疫反应。

Immunization of young heifers with staphylococcal immune evasion proteins before natural exposure to Staphylococcus aureus induces a humoral immune response in serum and milk.

作者信息

Benedictus Lindert, Ravesloot Lars, Poppe Kim, Daemen Ineke, Boerhout Eveline, van Strijp Jos, Broere Femke, Rutten Victor, Koets Ad, Eisenberg Susanne

机构信息

Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.

Division of Infection and Immunity, The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, Scotland, UK.

出版信息

BMC Vet Res. 2019 Jan 7;15(1):15. doi: 10.1186/s12917-018-1765-9.

Abstract

BACKGROUND

Staphylococcus aureus, a leading cause of mastitis in dairy cattle, causes severe mastitis and/or chronic persistent infections with detrimental effects on the cows' wellbeing, lifespan and milk production. Despite years of research there is no effective vaccine against S. aureus mastitis. Boosting of non-protective pre-existing immunity to S. aureus, induced by natural exposure to S. aureus, by vaccination may interfere with vaccine efficacy. The aim was to assess whether experimental immunization of S. aureus naïve animals results in an immune response that differs from immunity following natural exposure to S. aureus.

RESULTS

First, to define the period during which calves are immunologically naïve for S. aureus, Efb, LukM, and whole-cell S. aureus specific serum antibodies were measured in a cohort of newborn calves by ELISA. Rising S. aureus specific antibodies indicated that from week 12 onward calves mounted an immune response to S. aureus due to natural exposure. Next, an experimental immunization trial was set up using 8-week-old heifer calves (n = 16), half of which were immunized with the immune evasion molecules Efb and LukM. Immunization was repeated after one year and before parturition and humoral and cellular immunity specific for Efb and LukM was determined throughout the study. Post-partum, antibody levels against LukM and EfB were significantly higher in serum, colostrum and milk in the experimentally immunized animals compared to animals naturally exposed to S. aureus. LukM specific IL17a responses were also significantly higher in the immunized cows post-partum.

CONCLUSIONS

Experimental immunization with staphylococcal immune evasion molecules starting before natural exposure resulted in significantly higher antibody levels against Efb and LukM around parturition in serum as well as the site of infection, i.e. in colostrum and milk, compared to natural exposure to S. aureus. This study showed that it is practically feasible to vaccinate S. aureus naïve cattle and that experimental immunization induced a humoral immune response that differed from that after natural exposure only.

摘要

背景

金黄色葡萄球菌是奶牛乳腺炎的主要病因,可导致严重的乳腺炎和/或慢性持续性感染,对奶牛的健康、寿命和产奶量产生不利影响。尽管经过多年研究,但仍没有针对金黄色葡萄球菌乳腺炎的有效疫苗。通过接种疫苗增强由自然接触金黄色葡萄球菌诱导的对金黄色葡萄球菌的非保护性预先存在的免疫力,可能会干扰疫苗效力。目的是评估对未接触过金黄色葡萄球菌的动物进行实验性免疫是否会产生与自然接触金黄色葡萄球菌后产生的免疫反应不同的免疫反应。

结果

首先,为了确定犊牛对金黄色葡萄球菌免疫未成熟的时期,通过ELISA在一组新生犊牛中检测了Efb、LukM和全细胞金黄色葡萄球菌特异性血清抗体。金黄色葡萄球菌特异性抗体水平升高表明,从第12周起,犊牛由于自然接触而对金黄色葡萄球菌产生了免疫反应。接下来,使用8周龄的小母牛犊牛(n = 16)进行了一项实验性免疫试验,其中一半用免疫逃避分子Efb和LukM进行免疫。在一年后和分娩前重复免疫,并在整个研究过程中测定对Efb和LukM的体液免疫和细胞免疫。产后,与自然接触金黄色葡萄球菌的动物相比,实验性免疫动物血清、初乳和乳汁中针对LukM和EfB的抗体水平显著更高。产后免疫奶牛中LukM特异性IL17a反应也显著更高。

结论

与自然接触金黄色葡萄球菌相比,在自然接触之前开始用葡萄球菌免疫逃避分子进行实验性免疫,导致分娩前后血清以及感染部位(即初乳和乳汁)中针对Efb和LukM的抗体水平显著更高。这项研究表明,对未接触过金黄色葡萄球菌的牛进行疫苗接种在实际操作上是可行的,并且实验性免疫诱导的体液免疫反应仅与自然接触后的反应不同。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2afd/6323680/d07662c3573a/12917_2018_1765_Fig1_HTML.jpg

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