Regulation of B cell responses to vaccines by long-term retention of antigens in germinal centres

通过在生发中心长期保留抗原来调节 B 细胞对疫苗的反应

• 批准号: MR/X009254/1
• 负责人: Pavel Tolar
• 金额: $ 298.02万
• 依托单位: University College London
• 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=MR%2FX009254%2F1
• 关键词: Regulation; cell; responses; vaccines; long

Vaccines have eliminated the danger of many lethal infections and remain the best tool to combat new pathogens. However, traditional vaccines have limitations and don't protect well from rapidly changing or otherwise sophisticated pathogens. Vaccines also take time to develop and often require several doses to achieve good protection, delaying their efficacy against emerging threats. One of the possible advancements in vaccine design is to improve the entry of vaccine material into draining lymph nodes and make them persist long enough to stimulate a strong immune response. Retention of the vaccine over time is particularly important to generate protective antibodies which take several weeks to develop. We have identified a specific type of accessory immune cells that capture and keep foreign materials in lymph nodes for long periods of time (weeks) and present them to immune cells called B lymphocytes, which produce antibodies. Our main aim is to determine the properties of these accessory cells so that we can understand how the retention of foreign materials works and how it helps B lymphocytes to produce antibodies of high quality. We use the new knowledge to evaluate current vaccine properties and develop improvements to generate a stronger antibody response with a lower dosage.

疫苗消除了许多致命感染的危险，仍然是对抗新病原体的最佳工具。然而，传统疫苗有局限性，不能很好地保护人们免受快速变化或其他复杂病原体的侵害。疫苗的开发也需要时间，而且往往需要几剂才能达到良好的保护效果，从而延缓了它们对新出现的威胁的效力。疫苗设计的一个可能的进步是改善疫苗物质进入引流淋巴结的能力，并使它们持续足够长的时间来刺激强烈的免疫反应。在一段时间内保留疫苗对于产生保护性抗体尤其重要，保护性抗体需要数周才能产生。我们已经确定了一种特殊类型的辅助免疫细胞，它可以捕获并保持淋巴结中的外来物质很长一段时间（数周），并将它们呈递给称为B淋巴细胞的免疫细胞，B淋巴细胞产生抗体。我们的主要目的是确定这些辅助细胞的特性，这样我们就可以了解外来物质的保留是如何起作用的，以及它是如何帮助B淋巴细胞产生高质量抗体的。我们利用这些新知识来评估当前疫苗的特性，并进行改进，以更低的剂量产生更强的抗体反应。