Driving protective immune responses by targeting Mycobacterium bovis and Foot-and-Mouth Disease virus antigens to bovine dendritic cell subsets

通过将牛分枝杆菌和口蹄疫病毒抗原靶向牛树突状细胞亚群来驱动保护性免疫反应

• 批准号: BB/F013590/1
• 负责人: Bryan Charleston
• 金额: $ 101.95万
• 依托单位: The Pirbright Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF013590%2F1
• 关键词: Driving; protective; immune; responses; targeting

These studies will help design new vaccines for two important diseases of cattle, bovine tuberculosis and Foot-and-Mouth disease virus. Mycobacterium bovis is the causative agent of bovine tuberculosis (TB), a disease increasing in incidence in UK cattle herds causing major economic losses and potential human health risks. At present control of bovine TB relies solely on the use of diagnostic tests which do not have 100% sensitivity or specificity. Foot and mouth disease virus (FMDV) has a wide host range including all cloven-hoofed animals and causes an acute vesicular disease in domestic ruminants and pigs, which results in debilitation, pain and loss of productivity. Vaccines have been shown to be highly valuable in controlling a variety of infectious diseases, including bacteria and viruses. However, effective vaccines require portions of the infectious agent to be delivered to specialised cells, called dendritic cells. Dendritic cells are the only cells in the body capable of starting an immune response to an agent the body hasn't seen before. Targeting portions of the infectious agents to dendritic cells has been shown to stimulate a strong immune response. Unfortunately, the situation is more complicated than it first appears, there is more than one type of dendritic cell and each cell type can stimulate a different type of immune response. Specific immune responses may be required to control different infections. Acute viral infections, for example Foot-and-Mouth disease, may require an antibody response to control infection. In contrast, slow growing bacterial infections, for example tuberculosis may require immune T cells to control them. In this programme of work we plan to target components of Foot-and-Mouth disease virus or cattle tuberculosis bacteria to particular dendritic cell subsets to determine whther a protective immune response can be stimulated

这些研究将有助于设计针对牛的两种重要疾病——牛结核病和口蹄疫病毒的新疫苗。牛分枝杆菌是牛结核病 (TB) 的病原体，这种疾病在英国牛群中发病率不断上升，造成重大经济损失和潜在的人类健康风险。目前，牛结核病的控制仅依赖于使用不具有 100% 敏感性或特异性的诊断测试。口蹄疫病毒 (FMDV) 的宿主范围广泛，包括所有偶蹄动物，可在家养反刍动物和猪中引起急性水疱病，导致虚弱、疼痛和生产力下降。疫苗已被证明在控制包括细菌和病毒在内的多种传染病方面具有很高的价值。然而，有效的疫苗需要将部分传染原递送至称为树突状细胞的特殊细胞。树突状细胞是体内唯一能够对身体以前从未见过的物质发起免疫反应的细胞。将部分传染原靶向树突状细胞已被证明可以刺激强烈的免疫反应。不幸的是，情况比最初出现的要复杂，树突状细胞的类型不止一种，每种细胞类型都可以刺激不同类型的免疫反应。可能需要特定的免疫反应来控制不同的感染。急性病毒感染，例如口蹄疫，可能需要抗体反应来控制感染。相比之下，生长缓慢的细菌感染，例如结核病，可能需要免疫 T 细胞来控制它们。在这个工作计划中，我们计划将口蹄疫病毒或牛结核病细菌的成分靶向特定的树突状细胞亚群，以确定是否可以刺激保护性免疫反应

项目成果

The relative magnitude of transgene-specific adaptive immune responses induced by human and chimpanzee adenovirus vectors differs between laboratory animals and a target species.

人类和黑猩猩腺病毒载体诱导的转基因特异性适应性免疫反应的相对强度在实验动物和目标物种之间是不同的。

• DOI: http://dx.10.1016/j.vaccine.2015.01.042
• 发表时间: 2015
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: Dicks MD

Transduction of skin-migrating dendritic cells by human adenovirus 5 occurs via an actin-dependent phagocytic pathway.

人腺病毒5对皮肤迁移树突状细胞的转导是通过肌动蛋白依赖性吞噬途径发生的。

• DOI: http://dx.10.1099/jgv.0.000581
• 发表时间: 2016
• 期刊: The Journal of general virology
• 作者: Guzman E

Migratory sub-populations of afferent lymphatic dendritic cells differ in their interactions with Mycobacterium bovis Bacille Calmette Guerin.

传入淋巴树突状细胞的迁移亚群与牛分枝杆菌卡介苗的相互作用不同。

• DOI: http://dx.10.1016/j.vaccine.2012.01.036
• 发表时间: 2012
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: Hope JC

Bovine ?d T cells are a major regulatory T cell subset.

牛δd T 细胞是主要的调节性T 细胞亚群。

• DOI: http://dx.10.4049/jimmunol.1303398
• 发表时间: 2014
• 期刊: 1950)
• 作者: Guzman E

Differential effects of viral vectors on migratory afferent lymph dendritic cells in vitro predict enhanced immunogenicity in vivo.

病毒载体对体外迁移性传入淋巴树突状细胞的不同作用预示着体内免疫原性的增强。

• DOI: http://dx.10.1128/jvi.05127-11
• 发表时间: 2011
• 期刊: Journal of virology
• 作者: Cubillos