医学部附属病院

中橋 理佳(旧姓 大内田)

ナカハシ リカ  (Nakahashi Rika)

基本情報

所属
千葉大学 医学部附属病院ヒト粘膜ワクチン学部門 特任准教授
学位
医学(2004年3月 東京大学)

研究者番号
80391887
J-GLOBAL ID
201901005943268263
researchmap会員ID
B000365461

研究キーワード

 2

論文

 48
  • Yoshikazu Yuki, Shiho Kurokawa, Kotomi Sugiura, Koji Kashima, Shinichi Maruyama, Tomoyuki Yamanoue, Ayaka Honma, Mio Mejima, Natsumi Takeyama, Masaharu Kuroda, Hiroko Kozuka-Hata, Masaaki Oyama, Takehiro Masumura, Rika Nakahashi-Ouchida, Kohtaro Fujihashi, Takashi Hiraizumi, Eiji Goto, Hiroshi Kiyono
    Frontiers in Plant Science 15 2024年3月15日  
    We previously established the selection-marker-free rice-based oral cholera vaccine (MucoRice-CTB) line 51A for human use by Agrobacterium-mediated co-transformation and conducted a double-blind, randomized, placebo-controlled phase I trial in Japan and the United States. Although MucoRice-CTB 51A was acceptably safe and well tolerated by healthy Japanese and U.S. subjects and induced CTB-specific antibodies neutralizing cholera toxin secreted by Vibrio cholerae, we were limited to a 6-g cohort in the U.S. trial because of insufficient production of MucoRice-CTB. Since MucoRice-CTB 51A did not grow in sunlight, we re-examined the previously established marker-free lines and selected MucoRice-CTB line 19A. Southern blot analysis of line 19A showed a single copy of the CTB gene. We resequenced the whole genome and detected the transgene in an intergenic region in chromosome 1. After establishing a master seed bank of MucoRice-CTB line 19A, we established a hydroponic production facility with LED lighting to reduce electricity consumption and to increase production capacity for clinical trials. Shotgun MS/MS proteomics analysis of MucoRice-CTB 19A showed low levels of α-amylase/trypsin inhibitor-like proteins (major rice allergens), which was consistent with the data for line 51A. We also demonstrated that MucoRice-CTB 19A had high oral immunogenicity and induced protective immunity against cholera toxin challenge in mice. These results indicate that MucoRice-CTB 19A is a suitable oral cholera vaccine candidate for Phase I and II clinical trials in humans, including a V. cholerae challenge study.
  • Zhongwei Zhang, Izumi Tanaka, Rika Nakahashi-Ouchida, Peter B Ernst, Hiroshi Kiyono, Yosuke Kurashima
    Seminars in immunopathology 2024年1月3日  
    Glycoprotein 2 (GP2) is a widely distributed protein in the digestive tract, contributing to mucosal barrier maintenance, immune homeostasis, and antigen-specific immune response, while also being linked to inflammatory bowel disease (IBD) pathogenesis. This review sheds light on the extensive distribution of GP2 within the gastrointestinal tract and its intricate interplay with the immune system. Furthermore, the significance of GP2 autoantibodies in diagnosing and categorizing IBD is underscored, alongside the promising therapeutic avenues for modulating GP2 to regulate immunity and maintain mucosal balance.
  • Yoshikazu Yuki, Norihiro Harada, Shin-Ichi Sawada, Yohei Uchida, Rika Nakahashi-Ouchida, Hiromi Mori, Tomoyuki Yamanoue, Tomonori Machita, Masakatsu Kanazawa, Dai Fukumoto, Hiroyuki Ohba, Takashi Miyazaki, Kazunari Akiyoshi, Kohtaro Fujihashi, Hiroshi Kiyono
    Vaccine 41(34) 4941-4949 2023年7月31日  
    Cationic cholesteryl-group-bearing pullulan nanogel (cCHP-nanogel) is an effective drug-delivery system for nasal vaccines. However, cCHP-nanogel-based nasal vaccines might access the central nervous system due to its close proximity via the olfactory bulb in the nasal cavity. Using real-time quantitative tracking of the nanogel-based nasal botulinum neurotoxin and pneumococcal vaccines, we previously confirmed the lack of deposition of vaccine antigen in the cerebrum or olfactory bulbs of mice and non-human primates (NHPs), rhesus macaques. Here, we used positron emission tomography to investigate the biodistribution of the drug-delivery system itself, cCHP-nanogel after mice and NHPs were nasally administered with 18F-labeled cCHP nanogel. The results generated by the PET analysis of rhesus macaques were consistent with the direct counting of radioactivity due to 18F or 111In in dissected mouse tissues. Thus, no depositions of cCHP-nanogel were noted in the cerebrum, olfactory bulbs, or eyes of both species after nasal administration of the radiolabeled cCHP-nanogel compound. Our findings confirm the safe biodistribution of the cCHP-nanogel-based nasal vaccine delivery system in mice and NHPs.
  • Shingo Umemoto, Rika Nakahashi-Ouchida, Yoshikazu Yuki, Shiho Kurokawa, Tomonori Machita, Yohei Uchida, Hiromi Mori, Tomoyuki Yamanoue, Takehiko Shibata, Shin-Ichi Sawada, Kazuya Ishige, Takashi Hirano, Kohtaro Fujihashi, Kazunari Akiyoshi, Yosuke Kurashima, Daisuke Tokuhara, Peter B Ernst, Masashi Suzuki, Hiroshi Kiyono
    NPJ vaccines 8(1) 106-106 2023年7月24日  
    Respiratory syncytial virus (RSV) is a leading cause of upper and lower respiratory tract infection, especially in children and the elderly. Various vaccines containing the major transmembrane surface proteins of RSV (proteins F and G) have been tested; however, they have either afforded inadequate protection or are associated with the risk of vaccine-enhanced disease (VED). Recently, F protein-based maternal immunization and vaccines for elderly patients have shown promising results in phase III clinical trials, however, these vaccines have been administered by injection. Here, we examined the potential of using the ectodomain of small hydrophobic protein (SHe), also an RSV transmembrane surface protein, as a nasal vaccine antigen. A vaccine was formulated using our previously developed cationic cholesteryl-group-bearing pullulan nanogel as the delivery system, and SHe was linked in triplicate to pneumococcal surface protein A as a carrier protein. Nasal immunization of mice and cotton rats induced both SHe-specific serum IgG and mucosal IgA antibodies, preventing viral invasion in both the upper and lower respiratory tracts without inducing VED. Moreover, nasal immunization induced greater protective immunity against RSV in the upper respiratory tract than did systemic immunization, suggesting a critical role for mucosal RSV-specific IgA responses in viral elimination at the airway epithelium. Thus, our nasal vaccine induced effective protection against RSV infection in the airway mucosa and is therefore a promising vaccine candidate for further development.
  • Rika Nakahashi-Ouchida, Kohtaro Fujihashi, Yosuke Kurashima, Yoshikazu Yuki, Hiroshi Kiyono
    Trends in Molecular Medicine 29(2) 124-140 2022年11月  
    Nasal vaccines induce pathogen-specific dual protective immunity at mucosal surfaces and systemically throughout the body. Consequently, nasal vaccines both prevent pathogen invasion and reduce disease severity. Because of these features, nasal vaccines are considered to be a next-generation tool for preventing respiratory infectious diseases, including COVID-19. However, nasal vaccines must overcome key safety concerns given the anatomic proximity of the central nervous system (CNS) via the olfactory bulbs which lie next to the nasal cavity. This review summarizes current efforts to develop safe and effective nasal vaccines and delivery systems, as well as their clinical applications for the prevention of respiratory infections. We also discuss various concerns regarding the safety of nasal vaccines and introduce a system for evaluating them.

共同研究・競争的資金等の研究課題

 12

産業財産権

 1