据介绍,疫苗抗原的结构完整性对产生保护性抗体反应至关重要,但蛋白酶活性对体内疫苗接种的影响尚不清楚。
研究人员对淋巴结中的蛋白酶活性进行了表征,发现抗原在囊下窦、皮质旁和滤泡间区域快速降解,而在滤泡树突状细胞(FDC)附近检测到低蛋白酶活性和抗原降解率。与这些发现相关的是,旨在将抗原靶向FDC的免疫方案导致了以完整抗原为主的生发中心,而传统免疫导致了同样以完整免疫原和抗原分解产物为靶标的弱得多的应答。
因此,空间分隔的抗原蛋白水解影响体液免疫,并能够加以利用。
附:英文原文
Title: Low protease activity in B cell follicles promotes retention of intact antigens after immunization
Author: Aereas Aung, Ang Cui, Laura Maiorino, Ava P. Amini, Justin R. Gregory, Maurice Bukenya, Yiming Zhang, Heya Lee, Christopher A. Cottrell, Duncan M. Morgan, Murillo Silva, Heikyung Suh, Jesse D. Kirkpatrick, Parastoo Amlashi, Tanaka Remba, Leah M. Froehle, Shuhao Xiao, Wuhbet Abraham, Josetta Adams, J. Christopher Love, Phillip Huyett, Douglas S. Kwon, Nir Hacohen, William R. Schief, Sangeeta N. Bhatia, Darrell J. Irvine
Issue&Volume: 2023-01-27
Abstract: The structural integrity of vaccine antigens is critical to the generation of protective antibody responses, but the impact of protease activity on vaccination in vivo is poorly understood. We characterized protease activity in lymph nodes and found that antigens were rapidly degraded in the subcapsular sinus, paracortex, and interfollicular regions, whereas low protease activity and antigen degradation rates were detected in the vicinity of follicular dendritic cells (FDCs). Correlated with these findings, immunization regimens designed to target antigen to FDCs led to germinal centers dominantly targeting intact antigen, whereas traditional immunizations led to much weaker responses that equally targeted the intact immunogen and antigen breakdown products. Thus, spatially compartmentalized antigen proteolysis affects humoral immunity and can be exploited.
DOI: abn8934
Source: https://www.science.org/doi/10.1126/science.abn8934