Files Megan A, Naqvi Kubra F, Saito Tais B, Clover Tara M, Rudra Jai S, Endsley Janice J
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
Institute of Translational Science, University of Texas Medical Branch, Galveston, TX, 77555, USA.
NPJ Vaccines. 2022 Apr 26;7(1):48. doi: 10.1038/s41541-022-00466-0.
Heterologous vaccine regimens could extend waning protection in the global population immunized with Mycobacterium bovis Bacille Calmette-Guerin (BCG). We demonstrate that pulmonary delivery of peptide nanofibers (PNFs) bearing an Ag85B CD4 T cell epitope increased the frequency of antigen-specific T cells in BCG-primed mice, including heterogenous populations with tissue resident memory (Trm) and effector memory (Tem) phenotype, and functional cytokine recall. Adoptive transfer of dendritic cells pulsed with Ag85B-bearing PNFs further expanded the frequency and functional repertoire of memory CD4 T cells. Transcriptomic analysis suggested that the adjuvanticity of peptide nanofibers is, in part, due to the release of damage-associated molecular patterns. A single boost with monovalent Ag85B PNF in BCG-primed mice did not reduce lung bacterial burden compared to BCG alone following aerosol Mtb challenge. These findings support the need for novel BCG booster strategies that activate pools of Trm cells with potentially diverse localization, trafficking, and immune function.
异源疫苗接种方案可能会延长全球接种卡介苗（BCG）人群中逐渐减弱的保护作用。我们证明，肺部递送携带Ag85B CD4 T细胞表位的肽纳米纤维（PNF）可增加卡介苗初免小鼠中抗原特异性T细胞的频率，包括具有组织驻留记忆（Trm）和效应记忆（Tem）表型的异质群体，以及功能性细胞因子召回。用携带Ag85B的PNF脉冲处理的树突状细胞的过继转移进一步扩大了记忆CD4 T细胞的频率和功能库。转录组分析表明，肽纳米纤维的佐剂活性部分归因于损伤相关分子模式的释放。与单独使用卡介苗相比，在气溶胶结核分枝杆菌攻击后，用单价Ag85B PNF对卡介苗初免小鼠进行单次加强免疫并没有降低肺部细菌负荷。这些发现支持了开发新型卡介苗加强策略的必要性，这些策略可激活具有潜在不同定位、迁移和免疫功能的Trm细胞池。
