Development of an in vitro system that mimics B and T helper cell responses in porcine lymph nodes

开发模拟猪淋巴结中 B 和 T 辅助细胞反应的体外系统

• 批准号: NC/X001113/1
• 负责人: Wilhelm Gerner
• 金额: $ 56.09万
• 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: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=NC%2FX001113%2F1
• 关键词: Development; vitro; system; mimics; helper

Pigs are kept in large numbers on farms in Europe and worldwide. To keep these animals healthy and to maintain a high standard of animal welfare, swine are frequently vaccinated. However, some of these vaccines have only limited efficacy and for some devastating pig diseases, like African swine fever, no vaccines exist at all.Hence, the testing and development of new vaccines is an area of active research by public research institutions and privately owned companies world-wide. Testing of vaccines from early stages of vaccine development onwards is mainly performed in living pigs. In this project we aim to develop a culture system for immune cells in the laboratory. Such a culture is called 'in vitro'. Our in vitro culture system mimics the immune response occurring in specialised organs of the immune system, called lymph nodes. Within these lymph nodes various immune cell types interact with each other. One of these cell types, called B cells, produces antibodies which often confer protection after vaccination. In pilot experiments, we have already established an in vitro system that shows several features of the immune reaction, like the activation of B cells and the production of antibodies. In the first phase of this project, we aim to optimise this system. Different variations will be introduced into the existing in vitro system to test whether they improve the function of the immune cells within them. In the final stage of the project, we will test if our optimised in vitro system is capable of mimicking central features of the B cell response, including antibody production, occurring in lymph nodes of living pigs. If our in vitro system proves to be capable of mimicking B cell and antibody responses occurring in living pigs, it will be used in the future to reduce the number of pigs in used in the development of new vaccine or improvement of current vaccines. This will apply to the early phase of vaccine development, where basic research is performed to identify promising vaccine candidates. Although the immune cells in our in vitro system still need to be isolated initially from a living pig, cells from a single pig can be used in numerous projects for the testing of different vaccine candidates. We will communicate the findings of our project to colleagues working in other research institutions and in vaccine-producing companies. For this we will participate in international scientific meetings, speak to colleagues via established collaboration networks, offer training courses and spread our findings via social media platforms. Results will also be published in scientific journals. In this way we ensure that our in vitro system will be quickly taken up by others, ensuring it unfolds the maximal opportunity to reduce the number pigs required in the early phase of the development of new vaccines.

欧洲和世界各地的农场大量饲养生猪。为了保持这些动物的健康并维持高标准的动物福利，猪经常接种疫苗。然而，其中一些疫苗的功效有限，对于一些毁灭性的猪病，如非洲猪瘟，根本不存在疫苗。因此，新疫苗的测试和开发是公共研究机构和私营机构积极研究的领域世界各地的公司。从疫苗开发的早期阶段开始，疫苗测试主要在活猪上进行。在这个项目中，我们的目标是在实验室开发免疫细胞培养系统。这种培养被称为“体外”。我们的体外培养系统模仿免疫系统的特殊器官（称为淋巴结）中发生的免疫反应。在这些淋巴结内，各种免疫细胞类型相互作用。其中一种细胞类型称为 B 细胞，可产生抗体，这些抗体通常在疫苗接种后提供保护。在试点实验中，我们已经建立了一个体外系统，该系统显示了免疫反应的几个特征，例如 B 细胞的激活和抗体的产生。在这个项目的第一阶段，我们的目标是优化这个系统。将在现有的体外系统中引入不同的变异，以测试它们是否能改善体内免疫细胞的功能。在该项目的最后阶段，我们将测试我们优化的体外系统是否能够模拟活猪淋巴结中发生的 B 细胞反应的核心特征，包括抗体的产生。如果我们的体外系统被证明能够模拟活猪中发生的 B 细胞和抗体反应，它将在未来用于减少用于开发新疫苗或改进现有疫苗的猪的数量。这将适用于疫苗开发的早期阶段，即进行基础研究以确定有希望的候选疫苗。尽管我们的体外系统中的免疫细胞最初仍需要从活猪中分离出来，但来自单头猪的细胞可以用于许多项目来测试不同的候选疫苗。我们将把我们项目的研究结果传达给其他研究机构和疫苗生产公司的同事。为此，我们将参加国际科学会议，通过已建立的合作网络与同事交流，提供培训课程并通过社交媒体平台传播我们的发现。结果也将发表在科学期刊上。通过这种方式，我们确保我们的体外系统能够迅速被其他系统采用，从而确保它提供最大的机会来减少新疫苗开发早期阶段所需的猪数量。