治療薬・ワクチン開発研究センター 第三室

令和6年4月2日
治療薬・ワクチン開発研究センター
(内線2134)

研究テーマ

1. 免疫原性と反応原性のバランスを考慮した新規ワクチン開発研究
2. ワクチンの免疫原性および反応原性の評価法開発研究
3. ワクチン接種に関する自然免疫学的研究
4. ウイルス感染症（新型コロナウイルス、ジカウイルス、デングウイルス、日本脳炎ウイルス等）に関する免疫学的研究
5. 細菌感染症（溶血性レンサ球菌、抗酸菌等）に関する免疫学的研究
6. はぶ、まむし、やまかがし、セアカゴケグモ抗毒素等の品質管理に関する研究

第三室の構成

最近の業績（2019年～）

1. Morino E, Mine S, Tomita N, Uemura Y, Shimizu Y, Saito S, Suzuki T, Okumura N, Iwasaki H, Terada J, Ainai A, Sakai Y, Park E, Seki S, Akazawa D, Shimojima M, Shiwa-Sudo N, Virhuez-Mendoza M, Miyauchi K, Moriyama S, Iwata-Yoshikawa N, Harada M, Harada S, Hishiki T, Kotaki R, Matsumura T, Miyamoto S, Kanno T, Isogawa M, Watashi K, Nagata N, Ebihara H, Takahashi Y, Maeda K, Matano T, Wakita T, Suzuki T, Sugiura W, Ohmagari N, Ujiie M✉. Mpox neutralizing antibody response to LC16m8 vaccine in healthy adults. NEJM Evid. 2024 Mar;3(3):EVIDoa2300290. doi: 10.1056/EVIDoa2300290.
2. Onodera T, Sax N, Sato T, Adachi Y, Kotaki R, Inoue T, Shinnakasu R, Nakagawa T, Fukushi S, Terooatea T, Yoshikawa M, Tonouchi K, Nagakura T, Moriyama S, Matsumura T, Isogawa M, Terahara K, Takano T, Sun L, Nishiyama A, Omoto S, Shinkai M, Kurosaki T, Yamashita K✉, Takahashi Y✉. CD62L expression marks SARS-CoV-2 memory B cell subset with preference for neutralizing epitopes. Sci Adv. 2023 Jun 16;9(24):eadf0661. doi: 10.1126/sciadv.adf0661.（概要はこちら）
3. Sasaki E✉, Asanuma H, Momose H, Furuhata K, Mizukami T, Matsumura T, Takahashi Y, Hamaguchi I. Systemically inoculated adjuvants stimulate pDC-dependent IgA response in local site. Mucosal Immunol. 2023 Jun;16(3):275-286. doi: 10.1016/j.mucimm.2023.03.003.
4. Takano T*, Sato T*, Kotaki R*, Moriyama S, Fukushi S, Shinoda M, Kabasawa K, Shimada N, Kousaka M, Adachi Y, Onodera T, Terahara K, Isogawa M, Matsumura T✉, Shinkai M✉, Takahashi Y✉. Heterologous SARS-CoV-2 spike protein booster elicits durable and broad antibody responses against the receptor-binding domain. Nat Commun. 2023 Mar 15;14(1):1451. doi: 10.1038/s41467-023-37128-1. (*equally contributed)
5. Wang Y, Takano T, Zhou Y, Wang R, Toshimitsu T, Sashihara T, Tanokura M, Miyakawa T, Nakajima-Adachi H, Hachimura S✉.Orally administered Lactiplantibacillus plantarum OLL2712 decreased intestinal permeability, especially in the ileum: Ingested lactic acid bacteria alleviated obesity-induced inflammation by collaborating with gut microbiota. Front Immunol. 2023 Feb 23;14:1123052. doi: 10.3389/fimmu.2023.1123052.
6. Kashima Y, Mizutani T, Nakayama-Hosoya K, Moriyama S, Matsumura T, Yoshimura Y, Sasaki H, Horiuchi H, Miyata N, Miyazaki K, Tachikawa N, Takahashi Y, Suzuki T, Sugano S, Matano T, Kawana-Tachikawa A, Suzuki Y✉. Multimodal single-cell analyses of peripheral blood mononuclear cells of COVID-19 patients in Japan. Sci Rep. 2023 Feb 2;13(1):1935. doi: 10.1038/s41598-023-28696-9.
7. Matsumura T✉, Takano T, Takahashi Y. Immune responses related to the immunogenicity and reactogenicity of COVID-19 mRNA vaccines. Int Immunol. 2023 May 8;35(5):213-220. doi: 10.1093/intimm/dxac064.
8. Terahara K, Sato T, Adachi Y, Tonouchi K, Onodera T, Moriyama S, Sun L, Takano T, Nishiyama A, Kawana-Tachikawa A, Matano T, Matsumura T, Shinkai M, Isogawa M✉, Takahashi Y✉. SARS-CoV-2 specific CD4+ T cell longevity correlates with Th17-like phenotype. iScience. 2022 Sep 16;25(9):104959. doi: 10.1016/j.isci.2022.104959.
9. Wang R, Nakajima-Adachi H, Wang Y, Zhou Y, Gu W, Hiraide E, Morinaga M, Nakagawa R, Nakamura S, Takano T, Li X, Saeki M, Kaminuma O, Hiroi T, Uchida K, Motoshima H, Tanokura M✉, Miyakawa T✉, Hachimura S✉. Regulation of Th2 responses by Lactococcus lactis subsp. cremoris YRC3780 alleviates DNCB-induced atopic dermatitis in the mouse model. J Funct Foods. 2022 July;94:105091. doi: 10.1016/j.jff.2022.105091.
10. Zhou Y, Takano T, Li X, Wang Y, Wang R, Zhu Z, Tanokura M, Miyakawa T✉, Hachimura S✉. β-elemene regulates M1-M2 macrophage balance through the ERK/JNK/P38 MAPK signaling pathway. Commun Biol. 2022 May 31;5(1):519. doi: 10.1038/s42003-022-03369-x.
11. Takano T*, Morikawa K*, Adachi Y, Kabasawa K, Sax N, Moriyama S, Sun L, Isogawa M, Nishiyama A, Onodera T, Terahara K, Tonouchi K, Nishimura M, Tomii K, Yamashita K, Matsumura T✉, Shinkai M✉, Takahashi Y✉. Distinct immune cell dynamics correlate with the immunogenicity and reactogenicity of SARS-CoV-2 mRNA vaccine. Cell Rep Med. 2022 May 17;3(5):100631. doi: 10.1016/j.xcrm.2022.100631. (*equally contributed)（概要はこちら）
12. Shinada K, Sato T✉, Moriyama S, Adachi Y, Shinoda M, Ota S, Morikawa M, Mineshita M, Matsumura T, Takahashi Y, Shinkai M. Longitudinal analysis of neutralizing potency against SARS-CoV-2 in the recovered patients after treatment with or without Favipiravir. Viruses. 2022 Mar 24;14(4):670. doi: 10.3390/v14040670.
13. Kotaki R*, Adachi Y*, Moriyama S*, Onodera T*, Fukushi S, Nagakura T, Tonouchi K, Terahara K, Sun L, Takano T, Nishiyama A, Shinkai M, Oba K, Nakamura-Uchiyama F, Shimizu H, Suzuki T, Matsumura T, Isogawa M, Takahashi Y✉. SARS-CoV-2 Omicron-neutralizing memory B-cells are elicited by two doses of BNT162b2 mRNA vaccine. Sci Immunol. 2022 Apr 22;7(70):eabn8590. doi: 10.1126/sciimmunol.abn8590. (*equally contributed)（概要はこちら）
14. Lu X, Hosono Y, Nagae M, Ishizuka S, Ishikawa E, Motooka D, Ozaki Y, Sax N, Maeda Y, Kato Y, Morita T, Shinnakasu R, Inoue T, Onodera T, Matsumura T, Shinkai M, Sato T, Nakamura S, Mori S, Kanda T, Nakayama EE, Shioda T, Kurosaki T, Takeda K, Kumanogoh A, Arase H, Nakagami H, Yamashita K, Takahashi Y, Yamasaki S✉. Identification of conserved SARS-CoV-2 spike epitopes that expand public cTfh clonotypes in mild COVID-19 patients. J Exp Med. 2021 Dec 6;218(12):e20211327. doi: 10.1084/jem.20211327.
15. Ono-Ohmachi A, Yamada S, Uno S, Tamai M, Soga K, Nakamura S, Udagawa N, Nakamichi Y, Koide M, Morita Y, Takano T, Itoh T, Kakuta S, Morimoto C, Matsuoka S, Iwakura Y, Tomura M, Kiyono H, Hachimura S, Nakajima-Adachi H✉. Effector memory CD4+T cells in mesenteric lymph nodes mediate bone loss in food-allergic enteropathy model mice, creating IL-4 dominance. Mucosal Immunol. 2021 Nov;14(6):1335-1346. doi: 10.1038/s41385-021-00434-2.
16. Miki S, Sasaki H✉, Horiuchi H, Miyata N, Yoshimura Y, Miyazaki K, Matsumura T, Takahashi Y, Suzuki T, Matano T, Kawana-Tachikawa A, Tachikawa N. On-admission SARS-CoV-2 RNAemia as a single potent predictive marker of critical condition development and mortality in COVID-19. PLoS One. 2021 Jul 13;16(7):e0254640. doi: 10.1371/journal.pone.0254640.
17. Moriyama S*, Adachi Y*, Sato T, Tonouchi K, Sun L, Fukushi S, Yamada S, Kinoshita H, Nojima K, Kanno T, Tobiume M, Ishijima K, Kuroda Y, Park ES, Onodera T, Matsumura T, Takano T, Terahara K, Isogawa M, Nishiyama A, Kawana-Tachikawa A, Shinkai M, Tachikawa N, Nakamura S, Okai T, Okuma K, Matano T, Fujimoto T, Maeda K, Ohnishi M, Wakita T, Suzuki T, Takahashi Y✉. Temporal maturation of neutralizing antibodies in COVID-19 convalescent individuals improves potency and breadth to circulating SARS-CoV-2 variants. Immunity. 2021 Aug 10;54(8)1841-1852.e4. doi: 10.1016/j.immuni.2021.06.015. (*equally contributed)（概要はこちら）
18. Anzurez A, Naka I, Miki S, Hosoya-Nakayama K, Isshiki M, Watanabe Y, Nakamura-Hoshi M, Seki S, Matsumura T, Takano T, Onodera T, Adachi Y, Moriyama S, Terahara K, Tachikawa N, Yoshimura Y, Sasaki H, Horiuchi H, Miyata N, Miyazaki K, Koga M, Ikeuchi K, Nagai H, Saito M, Adachi E, Yotsuyanagi H, Kutsuna S, Kawashima A, Miyazato Y, Kinoshita N, Kouno C, Tanaka K, Takahashi Y, Suzuki T, Matano T, Ohashi J✉, Kawana-Tachikawa A✉. Association of HLA-DRB1*09:01 with severe COVID-19. HLA. 2021 Jul;98(1):37-42. doi: 10.1111/tan.14256.
19. Morokuma K✉, Matsumura T, Yamamoto A, Sakai A, Hifumi T, Ato M, Takahashi M. Evaluation of the stability of Yamakagashi (Rhabdophis tigrinus) equine antivenom after 20 years storage. Trop Biomed. 2021 Jun 30;38(2):111-118. doi: 10.47665/tb.38.2.042.
20. Zhou Y, Qiu W, Wang Y, Wang R, Takano T, Li X, Zhu Z, Nakajima-Adachi H, Tanokura M✉, Hachimura S✉, Miyakawa T✉. β-Elemene suppresses obesity-induced imbalance in the microbiota-gut-brain axis. Biomedicines. 2021 Jun 22;9(7):704. doi: 10.3390/biomedicines9070704.
21. Takano T, Matsumura T✉, Adachi Y, Terahara K, Moriyama S, Onodera T, Nishiyama A, Kawana-Tachikawa A, Miki S, Hosoya-Nakayama K, Nakamura-Hoshi M, Seki S, Tachikawa N, Yoshimura Y, Miyata N, Horiuchi H, Sasaki H, Miyazaki K, Kinoshita N, Sudo T, Akiyama Y, Sato R, Suzuki T, Matano T, Takahashi Y✉. Myeloid cell dynamics correlating with clinical outcomes of severe COVID-19 in Japan. Int Immunol. 2021 Mar 31;33(4):241-247. doi: 10.1093/intimm/dxab005.（EDITOR'S CHOICEに選ばれました）
22. Zhou Y, Takano T, Wang Y, Li X, Wang R, Wakatsuki Y, Nakajima-Adachi H, Tanokura M, Miyakawa T✉, Hachimura S✉. Intestinal regulatory T cell induction by β-elemene alleviates the formation of fat tissue-related inflammation. iScience. 2020 Nov 30;24(1):101883. doi: 10.1016/j.isci.2020.101883. eCollection 2021 Jan 22.
23. Matsumura T✉, Takahashi Y. The role of myeloid cells in prevention and control of group A streptococcal infections. Biosaf Health. 2020 Sep; 2(3):130-134. doi: 10.1016/j.bsheal.2020.05.006.
24. Matsumura T✉*, Nishiyama A*, Aiko M, Ainai A, Ikebe T, Chiba J, Ato M, Takahashi Y✉. An anti-perfringolysin O monoclonal antibody cross-reactive with streptolysin O protects against streptococcal toxic shock syndrome. BMC Res Notes. 2020 Sep 5;13(1):419. doi: 10.1186/s13104-020-05264-2. (*equally contributed)
25. Takano T, Kotaki R, Park J, Yoshida T, Wakatsuki Y, Tanokura M, Miyakawa T, Takahashi K, Nakajima-Adachi H, Hachimura S✉. Age-dependent decrease in the induction of regulatory T cells is associated with decreased expression of RALDH2 in mesenteric lymph node dendritic cells. Front Immunol. 2020 Aug 11;11:1555. doi: 10.3389/fimmu.2020.01555.
26. Nithichanon A, Chetchotisakd P, Matsumura T, Takahashi Y, Ato M, Sakagami T, Lertmemongkolchai G✉. Diagnosis of NTM active infection in lymphadenopathy patients with anti-interferon-gamma auto-antibody using inhibitory ELISA vs. indirect ELISA. Sci Rep. 2020 Jun 2;10(1):8968. doi: 10.1038/s41598-020-65933-x.
27. Li X, Miyakawa T, Takano T, Nakajima-Adachi H, Tanokura M, Hachimura S✉. Induction of oral tolerance by pepsin-digested gliadin retaining T cell reactivity in a mouse model of wheat allergy. Int Arch Allergy Immunol. 2020;181(6):446-455. doi: 10.1159/000506945.
28. Han K, Song H, Choi CW, Park S, Kang YS, Jung K, Lee BH, Takahashi Y, Matsumura T, Yamamoto A, Kim YJ, Jee S, Kim J✉. Standardization of the first Korean national reference standard for snake (Gloydius brevicaudus) antivenom. Toxicol Res. 2020 Apr 14; 36(4):407-413. doi: 10.1007/s43188-020-00047-0.
29. Yamamoto M, Abe C, Wakinaga S, Sakane K, Yumiketa Y, Taguchi Y, Matsumura T, Ishikawa K, Fujimoto J, Semba K, Miyauchi M, Akiyama T, Inoue J✉. TRAF6 maintains mammary stem cells and promotes pregnancy-induced mammary epithelial cell expansion. Commun Biol. 2019 Aug 6;2:292. doi: 10.1038/s42003-019-0547-7.
30. Yoshizawa S, Matsumura T, Ikebe T, Ichibayashi R, Fukui Y, Satoh T, Tsubota T, Honda M, Ishii Y, Tateda K, Ato M✉. Streptococcal toxic shock syndrome caused by β-hemolytic streptococci: Clinical features and cytokine and chemokine analyses of 15 cases. J Infect Chemother. 2019 May;25(5):355-361. doi: 10.1016/j.jiac.2019.01.006.
31. Matsumura T✉, Ikebe T, Arikawa K, Hosokawa M, Aiko M, Iguchi A, Togashi I, Kai S, Ohara S, Ohara N, Ohnishi M, Watanabe H, Kobayashi K, Takeyama H, Yamasaki S, Takahashi Y, Ato M. Sequential sensing by TLR2 and Mincle directs immature myeloid cells to protect against invasive group A streptococcal infection in mice. Cell Rep. 2019 Apr 9;27(2):561-571.e6. doi: 10.1016/j.celrep.2019.03.056.（概要はこちら）

(✉ corresponding author)

主な研究業績

1. Heterologous SARS-CoV-2 spike protein booster elicits durable and broad antibody responses against the receptor-binding domain（Nat Commun. 2023）
2. SARS-CoV-2 mRNAワクチンの免疫原性と副反応にそれぞれ相関する免疫細胞ダイナミクス（Cell Rep Med. 2022）
3. TLR2とMincleによる連続した感知は未熟骨髄系細胞に劇症型溶血性レンサ球菌感染症に対する防御免疫を誘導させる（Cell Rep. 2019）
4. Lipoteichoic acid anchor triggers Mincle to drive protective immunity against invasive group A Streptococcus infection（Proc Natl Acad Sci USA. 2018）
5. Critical roles for lipomannan and lipoarabinomannan in cell wall integrity of mycobacteria and pathogenesis of tuberculosis（mBio. 2013）
6. インターフェロンγを産生する未熟骨髄系細胞は劇症型A群レンサ球菌感染に対して防御的に働く（Nat Commun. 2012）