Low-frequency CD8+ T cells induced by SIGN-R1+ macrophage-targeted vaccine confer SARS-CoV-2 clearance in mice PMID: 39294173

ADC Targets in Oncology

2026-04-10

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

NPJ Vaccines. 2024 Sep 18;9(1):173. doi: 10.1038/s41541-024-00961-6.

Daisuke Muraoka ^# ¹ ² , Meng Ling Moi ^# ³ ⁴ , Osamu Muto ⁵ ⁶ , Takaaki Nakatsukasa ⁷ ⁸ , Situo Deng ⁷ , Chieko Takashima ⁹ , Rui Yamaguchi ⁵ ⁶ , Shin-Ichi Sawada ¹⁰ , Haruka Hayakawa ¹¹ , Thi Thanh Ngan Nguyen ¹² , Yasunari Haseda ¹³ , Takatoshi Soga ¹³ , Hirokazu Matsushita ⁹ , Hiroaki Ikeda ⁷ , Kazunari Akiyoshi ¹⁴ , Naozumi Harada ¹³

Affiliations

1. Department of Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. [email protected].
2. Division of Translational Oncoimmunology, Aichi Cancer Center Research Institute, Nagoya, Japan. [email protected].
3. School of International Health, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan. [email protected].
4. Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan. [email protected].
5. Division of Cancer Systems Biology, Aichi Cancer Center Research Institute, Nagoya, Japan.
6. Division of Cancer Informatics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
7. Department of Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
8. Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
9. Division of Translational Oncoimmunology, Aichi Cancer Center Research Institute, Nagoya, Japan.
10. Synergy Institute for Futuristic Mucosal Vaccine Research and Development (cSIMVa), Chiba University, Chiba, Japan.
11. School of International Health, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
12. Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
13. United Immunity, Co., Ltd., Tokyo, 103-0022, Japan.
14. Department of Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
# Contributed equally.

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.