三苫 修也 (ミトマ シュウヤ)

MITOMA Shuya

写真a

所属

医学部 医学科 感染症学講座免疫学分野

職名

助教

外部リンク

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  • 博士(獣医学) ( 2021年3月   宮崎大学 )

  • 学士(獣医学) ( 2017年3月   宮崎大学 )

研究分野 【 表示 / 非表示

  • ライフサイエンス / 獣医学  / 免疫

学歴 【 表示 / 非表示

  • 宮崎大学   大学院医学獣医学総合研究科(博士課程・修士課程)   医学獣医学専攻(博士課程)

    2017年4月 - 2021年3月

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    国名:日本国

 

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  • The detection of long-lasting memory foot-and-mouth disease (FMD) virus serotype O-specific CD4<sup>+</sup> T cells from FMD-vaccinated cattle by bovine major histocompatibility complex class II tetramer 査読あり 国際共著 国際誌

    Mitoma S., Carr B.V., Harvey Y., Moffat K., Sekiguchi S., Charleston B., Norimine J., Seago J.

    Immunology   164 ( 2 )   266 - 278   2021年10月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Immunology  

    Foot-and-mouth disease (FMD) is a highly contagious, economically devastating disease of cloven-hooved animals. The development of long-lasting effective FMD vaccines would greatly benefit the global FMD control programme. Deep analysis of adaptive immunity in cattle vaccinated against FMD is technically challenging due to the lack of species-specific tools. In this study, we aimed to identify CD4+ T-cell epitopes in the FMD virus (FMDV) capsid and to phenotype the CD4+ T cells that recognize them using bovine major histocompatibility complex (BoLA) class II tetramer. A BoLA class II tetramer based on the DRA/DRB3*020:02 allele and FMDV antigen-stimulated PBMCs from bovine vaccinates were used to successfully identify four epitopes in the FMDV capsid, three of which have not been previously reported; two epitopes were identified in the structural protein VP1, one in VP3 and one in VP4. Specificity of the three novel epitopes was confirmed by proliferation assay. All epitope-expanded T-cell populations produced IFN-γ in vitro, indicating a long-lasting Th1 cell phenotype after FMD vaccination. VP3-specific CD4+ T cells exhibited the highest frequency amongst the identified epitopes, comprising >0·004% of the CD4+ T-cell population. CD45RO+CCR7+ defined central memory CD4+ T-cell subpopulations were present in higher frequency in FMDV-specific CD4+ T-cell populations from FMD-vaccinated cattle ex vivo. This indicates an important role in maintaining cell adaptive immunity after FMD vaccination. Notably, FMDV epitope-loaded tetramers detected the presence of FMDV-specific CD4+ T cells in bovine PBMC more than four years after vaccination. This work contributes to our understanding of vaccine efficacy.

    DOI: 10.1111/imm.13367

    Scopus

    PubMed

  • Characterization of the evolutionary and virological aspects of mutations in the receptor binding motif of the SARS-CoV-2 spike protein 査読あり

    Yuuka Masuda, Hesham Nasser, Jiri Zahradnik, Shuya Mitoma, Ryo Shimizu, Kayoko Nagata, Akifumi Takaori-Kondo, Gideon Schreiber, Kotaro Shirakawa, Akatsuki Saito, Terumasa Ikeda, Jumpei Ito, Kei Sato

    Frontiers in Virology   3   2023年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Frontiers Media SA  

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has substantially diversified during the pandemic, resulting in the successive emergence of variants characterized by various mutations. It has been observed that several epidemic variants, including those classified as variants of concern, share mutations at four key residues (L452R, T478K, E484K, and N501Y) within the receptor binding motif (RBM) region of the spike protein. However, the processes through which these four specific RBM mutations were acquired during the evolution of SARS-CoV-2, as well as the degree to which they enhance viral fitness, remain unclear. Moreover, the effect of these mutations on the properties of the spike protein is not yet fully understood. In this study, we performed a comprehensive phylogenetic analysis and showed that the four RBM mutations have been convergently acquired across various lineages throughout the evolutionary history of SARS-CoV-2. We also found a specific pattern in the order of acquisition for some of these mutations. Additionally, our epidemic dynamic modeling demonstrated that acquiring these mutations leads to an increase in the effective reproduction number of the virus. Furthermore, we engineered mutant spike proteins with all feasible combinations of the four mutations, and examined their properties to uncover the influence that these mutations have on viral characteristics. Our results provide insights into the roles these four mutations play in shaping the viral characteristics, epidemic proliferation, and evolutionary pathway of SARS-CoV-2.

    DOI: 10.3389/fviro.2023.1328229

  • Multiple mutations of SARS-CoV-2 Omicron BA.2 variant orchestrate its virological characteristics 査読あり

    Kimura I., Yamasoba D., Nasser H., Ito H., Zahradnik J., Wu J., Fujita S., Uriu K., Sasaki J., Tamura T., Suzuki R., Deguchi S., Plianchaisuk A., Yoshimatsu K., Kazuma Y., Mitoma S., Schreiber G., Asakura H., Nagashima M., Sadamasu K., Yoshimura K., Takaori-Kondo A., Ito J., Shirakawa K., Takayama K., Irie T., Hashiguchi T., Nakagawa S., Fukuhara T., Saito A., Ikeda T., Sato K.

    Journal of Virology   97 ( 10 )   2023年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Virology  

    Previous studies on the Omicron BA.2 variant suggested that the virological characteristics of BA.2 are determined by the mutations in at least two different regions of the viral genome: in the BA.2 spike gene (enhancing viral fusogenicity and intrinsic pathogenicity) and the non-spike region of the BA.2 genome (leading to intrinsic pathogenicity attenuation). However, the mutations modulating the BA.2 virological properties remain elusive. In this study, we demonstrated that the L371F substitution in the BA.2 spike protein confers greater fusogenicity and intrinsic pathogenicity. Furthermore, we revealed that multiple mutations downstream of the spike gene in the BA.2 genome are responsible for attenuating intrinsic viral pathogenicity and replication capacity. As mutations in the SARS-CoV-2 variant spike proteins could modulate certain virological properties, such as immune evasion and infectivity, most studies have previously focused on spike protein mutations. Our results underpin the importance of non-spike protein-related mutations in SARS-CoV-2 variants. IMPORTANCE Most studies investigating the characteristics of emerging SARS-CoV-2 variants have been focusing on mutations in the spike proteins that affect viral infectivity, fusogenicity, and pathogenicity. However, few studies have addressed how naturally occurring mutations in the non-spike regions of the SARS-CoV-2 genome impact virological properties. In this study, we proved that multiple SARS-CoV-2 Omicron BA.2 mutations, one in the spike protein and another downstream of the spike gene, orchestrally characterize this variant, shedding light on the importance of Omicron BA.2 mutations out of the spike protein.

    DOI: 10.1128/jvi.01011-23

    Scopus

  • Clec4A4 Acts as a Negative Immune Checkpoint Regulator to Suppress Antitumor Immunity 査読あり

    Uto T., Fukaya T., Mitoma S., Nishikawa Y., Tominaga M., Choijookhuu N., Hishikawa Y., Sato K.

    Cancer Immunology Research   11 ( 9 )   1266 - 1279   2023年9月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Cancer Immunology Research  

    Clec4A4 is a C-Type lectin receptor (CLR) exclusively expressed on murine conventional dendritic cells (cDC) to regulate their activation status. However, the functional role of murine Clec4A4 (mClec4A4) in antitumor immunity remains unclear. Here, we show that mClec4A4 serves as a negative immune checkpoint regulator to impair antitumor immune responses. Deficiency of mClec4A4 lead to a reduction in tumor development, accompanied by enhanced antitumor immune responses and amelioration of the immunosuppressive tumor microenvironment (TME) mediated through the enforced activation of cDCs in tumor-bearing mice. Furthermore, antagonistic mAb to human CLEC4A (hCLEC4A), which is the functional orthologue of mClec4A4, exerted protection against established tumors without any apparent signs of immunerelated adverse events in hCLEC4A-Transgenic mice. Thus, our findings highlight the critical role of mClec4A4 expressed on cDCs as a negative immune checkpoint molecule in the control of tumor progression and provide support for hCLEC4A as a potential target for immune checkpoint blockade in tumor immunotherapy.

    DOI: 10.1158/2326-6066.CIR-22-0536

    Scopus

  • An inhaled ACE2 decoy confers protection against SARS-CoV-2 infection in preclinical models 査読あり

    Urano E., Itoh Y., Suzuki T., Sasaki T., Kishikawa J.I., Akamatsu K., Higuchi Y., Sakai Y., Okamura T., Mitoma S., Sugihara F., Takada A., Kimura M., Nakao S., Hirose M., Sasaki T., Koketsu R., Tsuji S., Yanagida S., Shioda T., Hara E., Matoba S., Matsuura Y., Kanda Y., Arase H., Okada M., Takagi J., Kato T., Hoshino A., Yasutomi Y., Saito A., Okamoto T.

    Science Translational Medicine   15 ( 711 )   2023年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Science Translational Medicine  

    The Omicron variant continuously evolves under the humoral immune pressure exerted by vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the resulting Omicron subvariants display further immune evasion and antibody escape. An engineered angiotensin-converting enzyme 2 (ACE2) decoy composed of high-affinity ACE2 and an IgG1 Fc domain could offer an alternative modality to neutralize SARS-CoV-2. We previously reported its broad spectrum and therapeutic potential in rodent models. Here, we demonstrate that the engineered ACE2 decoy retains neutralization activity against Omicron subvariants, including the currently emerging XBB and BQ.1 strains, which completely evade antibodies currently in clinical use. SARS-CoV-2, under the suboptimal concentration of neutralizing drugs, generated SARS-CoV-2 mutants escaping wild-type ACE2 decoy and monoclonal antibodies, whereas no escape mutant emerged against the engineered ACE2 decoy. Furthermore, inhalation of aerosolized decoys improved the outcomes of rodents infected with SARS-CoV-2 at a 20-fold lower dose than that of intravenous administration. Last, the engineered ACE2 decoy exhibited therapeutic efficacy for cynomolgus macaques infected with SARS-CoV-2. These results indicate that this engineered ACE2 decoy represents a promising therapeutic strategy to overcome immune-evading SARS-CoV-2 variants and that liquid aerosol inhalation could be considered as a noninvasive approach to enhance the efficacy of COVID-19 treatments.

    DOI: 10.1126/SCITRANSLMED.ADI2623

    Scopus

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MISC 【 表示 / 非表示

  • 決定論的手法を用いた肉用牛の外部導入における牛伝染性リンパ腫ウイルス感染のリスク評価

    藤原未歩, 牛谷雄一, 野津昂亮, EL-DAOUS Hala, 芹田光玲, 三苫修也, 乗峰潤三, 乗峰潤三, 関口敏, 関口敏

    獣医疫学雑誌   25 ( 1 )   2021年

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    掲載種別:速報,短報,研究ノート等(学術雑誌)  

    J-GLOBAL

講演・口頭発表等 【 表示 / 非表示

  • Selective cell stimulation with bovine interleukin-2 mutein and the distribution of bovine CD122 on the peripheral lymphocytes

    Shuya Mitoma, Tomofumi Uto, Tomohiro Fukaya, Moe Tominaga, Katsuaki Sato, Junzo Norimine

    第52回日本免疫学会学術集会  2024年1月17日 

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    開催年月日: 2024年1月17日 - 2024年1月19日

    記述言語:英語   会議種別:ポスター発表  

  • 外部導入牛における牛白血病ウイルス感染の定量的リスク分析

    野津昂亮, WIRATSUDAKUL Anuwat, 三苫修也, 乗峰潤三, 関口敏

    日本産業動物獣医学会(九州)・日本小動物獣医学会(九州)・日本獣医公衆衛生学会(九州)  2017年 

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    開催年月日: 2017年

    会議種別:口頭発表(一般)  

  • 宮崎県における肉用牛生産者を対象とした牛白血病対策に関する意識調査

    森山楓栞, 耕野拓一, 窪田さと子, 三苫修也, 目堅博久, 乗峰潤三, 関口敏

    日本産業動物獣医学会(九州)・日本小動物獣医学会(九州)・日本獣医公衆衛生学会(九州)  2017年 

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    開催年月日: 2017年

    会議種別:口頭発表(一般)  

科研費(文科省・学振・厚労省)獲得実績 【 表示 / 非表示

  • 牛伝染性リンパ腫ウイルス感染症に対するNK細胞選択的活性による防御免疫効果

    研究課題/領域番号:22K15013  2022年04月 - 2025年03月

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    三苫 修也

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    担当区分:研究代表者