Muraoka Daisuke, Moi Meng Ling, Muto Osamu, Nakatsukasa Takaaki, Deng Situo, Takashima Chieko, Yamaguchi Rui, Sawada Shin-Ichi, Hayakawa Haruka, Nguyen Thi Thanh Ngan, Haseda Yasunari, Soga Takatoshi, Matsushita Hirokazu, Ikeda Hiroaki, Akiyoshi Kazunari, Harada Naozumi
Department of Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Division of Translational Oncoimmunology, Aichi Cancer Center Research Institute, Nagoya, Japan.
NPJ Vaccines. 2024 Sep 18;9(1):173. doi: 10.1038/s41541-024-00961-6.
Vaccine-induced T cells and neutralizing antibodies are essential for protection against SARS-CoV-2. Previously, we demonstrated that an antigen delivery system, pullulan nanogel (PNG), delivers vaccine antigen to lymph node medullary macrophages and thereby enhances the induction of specific CD8 T cells. In this study, we revealed that medullary macrophage-selective delivery by PNG depends on its binding to a C-type lectin SIGN-R1. In a K18-hACE2 mouse model of SARS-CoV-2 infection, vaccination with a PNG-encapsulated receptor-binding domain of spike protein decreased the viral load and prolonged the survival in the CD8 T cell- and B cell-dependent manners. T cell receptor repertoire analysis revealed that although the vaccine induced T cells at various frequencies, low-frequency specific T cells mainly promoted virus clearance. Thus, the induction of specific CD8 T cells that respond quickly to viral infection, even at low frequencies, is important for vaccine efficacy and can be achieved by SIGN-R1 medullary macrophage-targeted antigen delivery.
疫苗诱导的T细胞和中和抗体对于预防新型冠状病毒（SARS-CoV-2）至关重要。此前，我们证明了一种抗原递送系统，即支链淀粉纳米凝胶（PNG），可将疫苗抗原递送至淋巴结髓质巨噬细胞，从而增强特异性CD8 T细胞的诱导。在本研究中，我们发现PNG对髓质巨噬细胞的选择性递送取决于其与C型凝集素SIGN-R1的结合。在SARS-CoV-2感染的K18-hACE2小鼠模型中，用包裹刺突蛋白受体结合域的PNG进行疫苗接种以依赖CD8 T细胞和B细胞的方式降低了病毒载量并延长了生存期。T细胞受体库分析表明，尽管疫苗以不同频率诱导T细胞，但低频特异性T细胞主要促进病毒清除。因此，即使在低频下，诱导对病毒感染快速反应的特异性CD8 T细胞对于疫苗效力很重要，并且可以通过靶向SIGN-R1髓质巨噬细胞的抗原递送来实现。
