Institute of Biomaterials & Biomedical Engineering , University of Toronto , Toronto , Ontario M5S 3G9 , Canada.
Terrence Donnelly Centre for Cellular & Biomolecular Research , University of Toronto , Toronto , Ontario M5S 3E1 , Canada.
Nano Lett. 2019 Oct 9;19(10):7226-7235. doi: 10.1021/acs.nanolett.9b02834. Epub 2019 Sep 17.
Lymph node follicles capture and retain antigens to induce germinal centers and long-lived humoral immunity. However, control over antigen retention has been limited. Here we discovered that antigen conjugated to nanoparticle carriers of different sizes impacts the intralymph node transport and specific cell interaction. We found that follicular dendritic cell (FDC) networks determine the intralymph node follicle fate of these nanoparticles by clearing smaller ones (5-15 nm) within 48 h and retaining larger ones (50-100 nm) for over 5 weeks. The 50-100 nm-sized nanoparticles had 175-fold more delivery of antigen at the FDC dendrites, 5-fold enhanced humoral immune responses of germinal center B cell formation, and 5-fold more antigen-specific antibody production over 5-15 nm nanoparticles. Our results show that we can tune humoral immunity by simply manipulating the carrier size design to produce effectiveness of vaccines.
淋巴结滤泡捕获并保留抗原，以诱导生发中心和长期的体液免疫。然而，对抗原保留的控制一直受到限制。在这里，我们发现，与不同大小的纳米颗粒载体结合的抗原会影响淋巴结内的运输和特定细胞的相互作用。我们发现，滤泡树突状细胞 (FDC) 网络通过在 48 小时内清除较小的（5-15nm）纳米颗粒，并保留较大的（50-100nm）纳米颗粒超过 5 周来决定这些纳米颗粒在淋巴结滤泡内的命运。50-100nm 大小的纳米颗粒在 FDC 树突上有 175 倍更多的抗原传递，5 倍增强生发中心 B 细胞形成的体液免疫反应，以及 5 倍更多的抗原特异性抗体产生超过 5-15nm 的纳米颗粒。我们的结果表明，我们可以通过简单地操纵载体大小设计来调节体液免疫，从而提高疫苗的效果。
