VACCINE. Development of a novel yeast-based oral subunit vaccine against Eimeria spp. in chickens

疫苗。

• 批准号: BB/P003931/1
• 负责人: Damer Blake
• 金额: $ 50.98万
• 依托单位: Royal Veterinary College
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FP003931%2F1
• 关键词: VACCINE.; Development; novel; yeast; based

Yeast species such as Saccharomyces cerevisiae are useful tools for the high yield production of recombinant proteins and have a Generally Regarded As Safe (GRAS) status. They are capable of performing several complex post-translational modifications that are not achieved in many other expression systems, and are easily grown to very high densities producing large quantities of stable particles. Recently, the idea of using S. cerevisiae as a delivery vehicle for cancer, viral, and bacterial vaccines has been explored, inducing robust humoral and cellular immune responses. In addition to using yeast to produce a vaccine antigen of interest, the yeast cell itself has been shown to have adjuvant-like properties and has the potential to activate both inflammatory and phagocytic receptors expressed on antigen-presenting cells. Our preliminary data demonstrates that freeze-drying recombinant yeast cultures expressing viral protein at their surface renders the recombinant yeast completely non-viable (unpublished). However, the freeze-drying process does not alter conformation of these proteins, as surface expression is equal in live and freeze-dried yeast as quantified by flow cytometry and Western blotting. This has interesting implications in vaccine design as a non-viable S. cerevisiae is not categorised as a genetically modified organism (GMO) and such a killed vaccine would not be subject to GMO regulations. Additionally there would be no need for refrigeration of the freeze-dried yeast, reducing transport and storage costs. Vaccines based upon S. cerevisiae are likely to be particularly valuable against diseases of farmed poultry, where safety, scalability, stability, delivery and cost are crucial. In one example modern poultry production relies on effective control of Eimeria, but current approaches using drugs and live vaccines require improvement. In recent years a panel of coccidial antigens have been identified as vaccine candidates, each individually capable of inducing up to a 65% reduction in oocyst output. Now, the focus is shifting from antigen discovery to antigen formulation and delivery with yeast being a leading option, especially given the importance of T-cell mediated responses in anticoccidial immunity.

酿酒酵母等酵母物种是高产重组蛋白生产的有用工具，并具有公认安全 (GRAS) 状态。它们能够进行许多其他表达系统无法实现的多种复杂的翻译后修饰，并且很容易生长到非常高的密度，产生大量稳定的颗粒。最近，人们探索了使用酿酒酵母作为癌症、病毒和细菌疫苗的递送载体的想法，以诱导强大的体液和细胞免疫反应。除了使用酵母生产感兴趣的疫苗抗原外，酵母细胞本身已被证明具有佐剂样特性，并且有可能激活抗原呈递细胞上表达的炎症和吞噬细胞受体。我们的初步数据表明，冷冻干燥表面表达病毒蛋白的重组酵母培养物使重组酵母完全无法存活（未发表）。然而，冷冻干燥过程不会改变这些蛋白质的构象，因为通过流式细胞术和蛋白质印迹定量，活酵母和冻干酵母的表面表达是相同的。这对疫苗设计具有有趣的影响，因为无法存活的酿酒酵母不被归类为转基因生物（GMO），并且这种灭活疫苗将不受转基因生物法规的约束。此外，冻干酵母无需冷藏，从而降低了运输和储存成本。基于酿酒酵母的疫苗可能对防治养殖家禽疾病特别有价值，因为安全性、可扩展性、稳定性、交付和成本至关重要。在一个例子中，现代家禽生产依赖于艾美耳球虫的有效控制，但目前使用药物和活疫苗的方法需要改进。近年来，一组球虫抗原已被确定为候选疫苗，每种抗原都能诱导卵囊产量减少高达 65%。现在，重点已从抗原发现转向抗原配制和递送，酵母是主要选择，特别是考虑到 T 细胞介导的反应在抗球虫免疫中的重要性。

项目成果

Differential expression of microRNAs in the caecal content and faeces of broiler chickens experimentally infected with Eimeria.

实验感染艾美球虫的肉鸡盲肠内容物和粪便中 microRNA 的差异表达。

• DOI: 10.1080/03079457.2022.2076581
• 发表时间: 2022
• 期刊: journal of the W.V.P.A
• 作者: Williams J

A Novel Whole Yeast-Based Subunit Oral Vaccine Against Eimeria tenella in Chickens.

• DOI: 10.3389/fimmu.2022.809711
• 发表时间: 2022
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Soutter F;Werling D;Nolan M;Küster T;Attree E;Marugán-Hernández V;Kim S;Tomley FM;Blake DP
• 通讯作者: Blake DP

Formulating a method to analyse the differential expression of co-occurrence networks for small-sampled microbiome data

制定一种分析小样本微生物组数据共现网络差异表达的方法

• DOI: 10.1145/3584371.3612969
• 发表时间: 2023
• 作者: Gadhia N

Transcriptome analysis of differentially expressed circRNAs miRNAs and mRNAs during the challenge of coccidiosis.

• DOI: 10.3389/fimmu.2022.910860
• 发表时间: 2022
• 期刊: Frontiers in immunology
• 影响因子: 7.3