Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.
Sci Immunol. 2021 Mar 19;6(57). doi: 10.1126/sciimmunol.abd8003.
Tissue-resident memory T cells (T) can profoundly enhance mucosal immunity, but parameters governing T induction by vaccination remain poorly understood. Here, we describe an approach exploiting natural albumin transport across the airway epithelium to enhance mucosal T generation by vaccination. Pulmonary immunization with albumin-binding amphiphile conjugates of peptide antigens and CpG adjuvant (amph-vaccines) increased vaccine accumulation in the lung and mediastinal lymph nodes (MLNs). Amph-vaccines prolonged antigen presentation in MLNs over 2 weeks, leading to 25-fold increased lung-resident T cell responses over traditional immunization and enhanced protection from viral or tumor challenge. Mimicking such prolonged exposure through repeated administration of soluble vaccine revealed that persistence of both antigen and adjuvant was critical for optimal T induction, mediated through T cell priming in MLNs after prime, and directly in the lung tissue after boost. Thus, vaccine persistence strongly promotes T induction, and amph-conjugates may provide a practical approach to achieve such kinetics in mucosal vaccines.
组织驻留记忆 T 细胞（T 细胞）可以显著增强黏膜免疫，但疫苗接种诱导 T 细胞的参数仍知之甚少。在这里，我们描述了一种利用白蛋白在气道上皮细胞中的天然转运来增强疫苗接种诱导黏膜 T 细胞生成的方法。用肽抗原和 CpG 佐剂的白蛋白结合两亲物缀合物（amph-vaccines）进行肺部免疫接种可增加疫苗在肺部和纵隔淋巴结（MLN）中的积累。Amph-vaccines 使 MLN 中抗原呈递延长了 2 周以上，导致肺驻留 T 细胞反应增加了 25 倍，对病毒或肿瘤挑战的保护作用增强。通过重复给予可溶性疫苗来模拟这种延长的暴露，表明抗原和佐剂的持续存在对于最佳 T 细胞诱导至关重要，这是通过在初次接种后在 MLN 中进行 T 细胞启动以及在加强接种后直接在肺部组织中进行的。因此，疫苗的持续存在可强烈促进 T 细胞的诱导，并且 amph 缀合物可能为在黏膜疫苗中实现这种动力学提供一种实用的方法。
