Bedford James G, Caminschi Irina, Wakim Linda M
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne 3000, Australia.
Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton 3800, Australia.
Vaccines (Basel). 2020 Oct 1;8(4):572. doi: 10.3390/vaccines8040572.
Rapid antigen clearance from the nasal mucosa is one of the major challenges in the development of intranasal vaccines. Here, we tested whether intranasal immunization with a chitosan-hydrogel vaccine, with in situ gelling properties, extended antigen retention time within the nasal mucosa. Intranasal immunization with a chitosan-hydrogel vaccine retained antigen within the upper respiratory tract (URT), while intranasal delivery of less viscous vaccines led to antigen accumulation within the lower airways. Interestingly, sustained antigen retention within the URT following chitosan-hydrogel vaccination boosted the number of vaccine-specific, tissue resident memory (Trm) CD8 T cells that developed within the nasal mucosa. Mice immunized with a chitosan-hydrogel vaccine loaded with influenza virus peptides developed a large pool of influenza-specific CD8 nasal Trm and these cells were highly protective during an influenza challenge. Our results describe an effective vaccine formulation that can be utilized to boost local immunity in the nasal mucosa.
鼻黏膜中抗原的快速清除是鼻内疫苗开发的主要挑战之一。在此，我们测试了具有原位凝胶化特性的壳聚糖水凝胶疫苗进行鼻内免疫是否能延长抗原在鼻黏膜内的保留时间。壳聚糖水凝胶疫苗鼻内免疫可使抗原保留在上呼吸道（URT），而鼻内递送粘性较小的疫苗则导致抗原在 lower airways 内积聚。有趣的是，壳聚糖水凝胶疫苗接种后 URT 内抗原的持续保留增加了在鼻黏膜内发育的疫苗特异性组织驻留记忆（Trm）CD8 T 细胞的数量。用负载流感病毒肽的壳聚糖水凝胶疫苗免疫的小鼠产生了大量流感特异性 CD8 鼻 Trm，并且这些细胞在流感攻击期间具有高度保护作用。我们的结果描述了一种有效的疫苗制剂，可用于增强鼻黏膜的局部免疫力。
