Low-frequency CD8+ T cells induced by SIGN-R1+ macrophage-targeted vaccine confer SARS-CoV-2 clearance in mice

Autor: Daisuke Muraoka, Meng Ling Moi, Osamu Muto, Takaaki Nakatsukasa, Situo Deng, Chieko Takashima, Rui Yamaguchi, Shin-ichi Sawada, Haruka Hayakawa, Thi Thanh Ngan Nguyen, Yasunari Haseda, Takatoshi Soga, Hirokazu Matsushita, Hiroaki Ikeda, Kazunari Akiyoshi, Naozumi Harada
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: npj Vaccines, Vol 9, Iss 1, Pp 1-17 (2024)
Druh dokumentu: article
ISSN: 2059-0105
DOI: 10.1038/s41541-024-00961-6
Popis: Abstract 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.
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