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

在欧洲和世界各地的农场里，猪被大量饲养。为了保持这些动物的健康和维持高标准的动物福利，猪经常接种疫苗。然而，这些疫苗中的一些只有有限的效力，对于一些毁灭性的猪疾病，如非洲猪瘟，根本不存在疫苗。因此，新疫苗的测试和开发是世界各地公共研究机构和私营公司积极研究的领域。从疫苗开发的早期阶段开始，疫苗测试主要在活猪身上进行。在这个项目中，我们的目标是在实验室开发一种免疫细胞培养系统。这样的培养被称为‘体外培养’。我们的体外培养系统模拟了免疫系统特殊器官中发生的免疫反应，称为淋巴结节。在这些淋巴结内，不同类型的免疫细胞相互作用。其中一种被称为B细胞的细胞会产生抗体，在接种疫苗后通常会产生保护作用。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，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。不同的变种将被引入现有的体外系统中，以测试它们是否改善了其中免疫细胞的功能。在项目的最后阶段，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B细胞反应的中心特征，包括抗体产生。如果我们的体外系统被证明能够模拟活猪的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，在这一阶段进行基础研究以确定有希望的候选疫苗。虽然我们的体外系统中的免疫细胞最初仍然需要从一头活猪中分离出来，但一头猪的细胞可以用于许多项目，以测试不同的候选疫苗。我们将把我们项目的发现传达给在其他研究机构和疫苗生产公司工作的同事。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谈，提供培训课程，并通过社交媒体平台传播我们的发现。研究结果还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将很快被其他人采用，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生猪数量。

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.