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Article ; Online: Glycoprotein 2 as a gut gate keeper for mucosal equilibrium between inflammation and immunity.

Zhang, Zhongwei / Tanaka, Izumi / Nakahashi-Ouchida, Rika / Ernst, Peter B / Kiyono, Hiroshi / Kurashima, Yosuke

2024

Abstract: 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. ... ...

Abstract	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.
Language	English
Publishing date	2024-01-03
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	2316828-6
ISSN	1863-2300 ; 1863-2297
ISSN (online)	1863-2300
ISSN	1863-2297
DOI	10.1007/s00281-023-00999-z
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Article ; Online: Correction: Glycoprotein 2 as a gut gate keeper for mucosal equilibrium between inflammation and immunity.

Zhang, Zhongwei / Tanaka, Izumi / Nakahashi-Ouchida, Rika / Ernst, Peter B / Kiyono, Hiroshi / Kurashima, Yosuke

Seminars in immunopathology

2024

Language	English
Publishing date	2024-04-22
Publishing country	Germany
Document type	Published Erratum
ZDB-ID	2316828-6
ISSN	1863-2300 ; 1863-2297
ISSN (online)	1863-2300
ISSN	1863-2297
DOI	10.1007/s00281-024-01002-z
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Article ; Online: Mucosal vaccines: wisdom from now and then.

Kiyono, Hiroshi / Yuki, Yoshikazu / Nakahashi-Ouchida, Rika / Fujihashi, Kohtaro

International immunology

2021 Volume 33, Issue 12, Page(s) 767–774

Abstract: The oral and nasal cavities are covered by the mucosal epithelium that starts at the beginning of the aero-digestive tract. These mucosal surfaces are continuously exposed to environmental antigens including pathogens and allergens and are thus equipped ... ...

Abstract	The oral and nasal cavities are covered by the mucosal epithelium that starts at the beginning of the aero-digestive tract. These mucosal surfaces are continuously exposed to environmental antigens including pathogens and allergens and are thus equipped with a mucosal immune system that mediates initial recognition of pathogenicity and initiates pathogen-specific immune responses. At the dawn of our scientific effort to explore the mucosal immune system, dental science was one of the major driving forces as it provided insights into the importance of mucosal immunity and its application for the control of oral infectious diseases. The development of mucosal vaccines for the prevention of dental caries was thus part of a novel approach that contributed to building the scientific foundations of the mucosal immune system. Since then, mucosal immunology and vaccines have gone on a scientific journey to become one of the major entities within the discipline of immunology. Here, we introduce our past and current efforts and future directions for the development of mucosal vaccines, specifically a rice-based oral vaccine (MucoRice) and a nanogel-based nasal vaccine, with the aim of preventing and controlling gastrointestinal and respiratory infectious diseases using the interdisciplinary fusion of mucosal immunology with agricultural science and biomaterial engineering, respectively.
MeSH term(s)	Communicable Diseases/immunology ; Immunity, Mucosal/immunology ; Vaccines/immunology
Chemical Substances	Vaccines
Language	English
Publishing date	2021-08-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1013745-2
ISSN	1460-2377 ; 0953-8178
ISSN (online)	1460-2377
ISSN	0953-8178
DOI	10.1093/intimm/dxab056
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Zs.A 2619: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Nasal vaccines: solutions for respiratory infectious diseases.

Nakahashi-Ouchida, Rika / Fujihashi, Kohtaro / Kurashima, Yosuke / Yuki, Yoshikazu / Kiyono, Hiroshi

Trends in molecular medicine

2022 Volume 29, Issue 2, Page(s) 124–140

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Humans ; Administration, Intranasal ; COVID-19/prevention & control ; Vaccines ; Communicable Diseases ; Respiratory Tract Infections/prevention & control ; Immunity, Mucosal
Chemical Substances	Vaccines
Language	English
Publishing date	2022-11-23
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2036490-8
ISSN	1471-499X ; 1471-4914
ISSN (online)	1471-499X
ISSN	1471-4914
DOI	10.1016/j.molmed.2022.10.009
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Zs.A 4345: Show issues

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Article ; Online: Cationic pullulan nanogel as a safe and effective nasal vaccine delivery system for respiratory infectious diseases.

Nakahashi-Ouchida, Rika / Yuki, Yoshikazu / Kiyono, Hiroshi

Human vaccines & immunotherapeutics

2018 Volume 14, Issue 9, Page(s) 2189–2193

Abstract: The mucosal surfaces of the respiratory and gastrointestinal tracts are continuously exposed to countless beneficial and pathologic antigens. These mucosal surfaces are thus equipped with an immune system that is unique from those elsewhere in the body; ... ...

Abstract	The mucosal surfaces of the respiratory and gastrointestinal tracts are continuously exposed to countless beneficial and pathologic antigens. These mucosal surfaces are thus equipped with an immune system that is unique from those elsewhere in the body; this unique system provides the first line of immune surveillance and defense against pathogen invasion. The sophisticated immune induction machinery in the aero-digestive tract involves mucosa-associated lymphoid tissues, including nasopharyngeal- and gut-associated lymphoid tissues, for the generation of antigen-specific humoral and cellular immune responses. Consequently, nasal or oral immunization with an appropriate vaccine delivery vehicle prompts the induction of protective immunity in both the mucosal and systemic compartments, leading to a double layer of protection against pathogens. To harness the benefits of mucosal vaccines, various mucosal antigen delivery vehicles are under development, and a cationic cholesteryl-group-bearing pullulan nanogel (cCHP nanogel) has emerged as a potent nasal vaccine delivery system for the induction of protective immunity against respiratory infections.
MeSH term(s)	Administration, Intranasal ; Drug Carriers/administration & dosage ; Drug Carriers/adverse effects ; Glucans/administration & dosage ; Glucans/adverse effects ; Humans ; Polyethylene Glycols/administration & dosage ; Polyethylene Glycols/adverse effects ; Polyethyleneimine/administration & dosage ; Polyethyleneimine/adverse effects ; Respiratory Tract Infections/prevention & control ; Vaccines/administration & dosage ; Vaccines/adverse effects
Chemical Substances	Drug Carriers ; Glucans ; NanoGel ; Vaccines ; Polyethylene Glycols (3WJQ0SDW1A) ; pullulan (8ZQ0AYU1TT) ; Polyethyleneimine (9002-98-6)
Language	English
Publishing date	2018-07-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2664176-8
ISSN	2164-554X ; 2164-5515
ISSN (online)	2164-554X
ISSN	2164-5515
DOI	10.1080/21645515.2018.1461298
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Zs.A 6967: Show issues

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Article: MucoRice-CTB line 19A, a new marker-free transgenic rice-based cholera vaccine produced in an LED-based hydroponic system.

Yuki, Yoshikazu / Kurokawa, Shiho / Sugiura, Kotomi / Kashima, Koji / Maruyama, Shinichi / Yamanoue, Tomoyuki / Honma, Ayaka / Mejima, Mio / Takeyama, Natsumi / Kuroda, Masaharu / Kozuka-Hata, Hiroko / Oyama, Masaaki / Masumura, Takehiro / Nakahashi-Ouchida, Rika / Fujihashi, Kohtaro / Hiraizumi, Takashi / Goto, Eiji / Kiyono, Hiroshi

Frontiers in plant science

2024 Volume 15, Page(s) 1342662

Abstract: We previously established the selection-marker-free rice-based oral cholera vaccine (MucoRice-CTB) line 51A for human use ... ...

Abstract	We previously established the selection-marker-free rice-based oral cholera vaccine (MucoRice-CTB) line 51A for human use by
Language	English
Publishing date	2024-03-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2613694-6
ISSN	1664-462X
ISSN	1664-462X
DOI	10.3389/fpls.2024.1342662
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Article ; Online: Development of a nanogel-based nasal vaccine as a novel antigen delivery system.

Nakahashi-Ouchida, Rika / Yuki, Yoshikazu / Kiyono, Hiroshi

Expert review of vaccines

2017 Volume 16, Issue 12, Page(s) 1231–1240

Abstract: Introduction: Nasal vaccination is one of the most effective immunization methods because it can induce effective antigen-specific immune responses not only at the mucosal site of administration but also at distant mucosal surfaces, as well as in the ... ...

Abstract	Introduction: Nasal vaccination is one of the most effective immunization methods because it can induce effective antigen-specific immune responses not only at the mucosal site of administration but also at distant mucosal surfaces, as well as in the systemic compartment. Based on this advantage, many nasal vaccines are being developed and some have been licensed and marketed for clinical use. However, some have been withdrawn because of unacceptable adverse events such as inactivated influenza vaccine administrated with a heat-labile enterotoxin of Escherichia coli as an adjuvant. Thus, it is important to consider both the efficacy and safety of nasal vaccines. Areas covered: This review describes the benefits of cholesteryl group-bearing pullulan (CHP) nanogels for nasal vaccine delivery and vaccine development identified on Pubmed database with the term 'Nanogel-based nasal vaccine'. Expert commentary: CHP nanogels have been developed as novel drug delivery system, and a cationic CHP nanogels have been demonstrated to induce effective immunity as a nasal vaccine antigen carrier. Since vaccine antigens incorporated into CHP nanogels have exhibited no brain deposition after nasal administration in mice and nonhuman primates, the vaccine seems safe, and could be a promising new delivery system.
MeSH term(s)	Administration, Intranasal ; Animals ; Drug Delivery Systems ; Drug Evaluation, Preclinical ; Mice ; Polyethylene Glycols/administration & dosage ; Polyethylene Glycols/adverse effects ; Polyethyleneimine/administration & dosage ; Polyethyleneimine/adverse effects ; Primates ; Vaccines/administration & dosage ; Vaccines/adverse effects ; Vaccines/immunology
Chemical Substances	NanoGel ; Vaccines ; Polyethylene Glycols (30IQX730WE) ; Polyethyleneimine (9002-98-6)
Language	English
Publishing date	2017
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2181284-6
ISSN	1744-8395 ; 1476-0584
ISSN (online)	1744-8395
ISSN	1476-0584
DOI	10.1080/14760584.2017.1395702
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 6077: Show issues

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Article ; Online: Biodistribution assessment of cationic pullulan nanogel, a nasal vaccine delivery system, in mice and non-human primates.

Yuki, Yoshikazu / Harada, Norihiro / Sawada, Shin-Ichi / Uchida, Yohei / Nakahashi-Ouchida, Rika / Mori, Hiromi / Yamanoue, Tomoyuki / Machita, Tomonori / Kanazawa, Masakatsu / Fukumoto, Dai / Ohba, Hiroyuki / Miyazaki, Takashi / Akiyoshi, Kazunari / Fujihashi, Kohtaro / Kiyono, Hiroshi

Vaccine

2023 Volume 41, Issue 34, Page(s) 4941–4949

Abstract: 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 ... ...

Abstract	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
MeSH term(s)	Animals ; Nanogels ; Macaca mulatta ; Tissue Distribution ; Drug Delivery Systems ; Administration, Intranasal ; Pneumococcal Vaccines
Chemical Substances	polyethylene glycol polyethyleneimine nanogel ; Nanogels ; pullulan (8ZQ0AYU1TT) ; Pneumococcal Vaccines
Language	English
Publishing date	2023-06-27
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2023.06.065
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Zs.A 1930: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 458: Show issues

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Article ; Online: Biodistribution assessment of cationic pullulan nanogel, a nasal vaccine delivery system, in mice and non-human primates

Yuki, Yoshikazu / Harada, Norihiro / Sawada, Shin-ichi / Uchida, Yohei / Nakahashi-Ouchida, Rika / Mori, Hiromi / Yamanoue, Tomoyuki / Machita, Tomonori / Kanazawa, Masakatsu / Fukumoto, Dai / Ohba, Hiroyuki / Miyazaki, Takashi / Akiyoshi, Kazunari / Fujihashi, Kohtaro / Kiyono, H.

Vaccine. 2023 June 27,

2023

Abstract: 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 ... ...

Abstract	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.
Keywords	Streptococcus pneumoniae ; antigens ; botulinum toxin ; cerebrum ; intranasal administration ; mice ; nanogels ; nasal cavity ; olfactory bulb ; positron-emission tomography ; pullulan ; radioactivity ; radiolabeling ; vaccines ; Nasal vaccine ; Drug delivery system ; Positron emission tomography (PET) ; Biodistribution ; Mouse ; Non-human primate ; cCHP nanogel ; CDI ; CHI ; CNS ; CHP ; DDS ; DOTA-NHS-ester ; HPLC ; K[2,2,2] ; LNP ; MRI ; NALT ; NHP ; OB ; PBS ; percent ID (%ID) ; PET ; PspA ; SFB ; SUV ; TSTU
Language	English
Dates of publication	2023-0627
Publishing place	Elsevier Ltd
Document type	Article ; Online
Note	Pre-press version
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2023.06.065
Database	NAL-Catalogue (AGRICOLA)

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Zs.A 1930: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 458: Show issues

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Article ; Online: Cationic-nanogel nasal vaccine containing the ectodomain of RSV-small hydrophobic protein induces protective immunity in rodents.

Umemoto, Shingo / Nakahashi-Ouchida, Rika / Yuki, Yoshikazu / Kurokawa, Shiho / Machita, Tomonori / Uchida, Yohei / Mori, Hiromi / Yamanoue, Tomoyuki / Shibata, Takehiko / Sawada, Shin-Ichi / Ishige, Kazuya / Hirano, Takashi / Fujihashi, Kohtaro / Akiyoshi, Kazunari / Kurashima, Yosuke / Tokuhara, Daisuke / Ernst, Peter B / Suzuki, Masashi / Kiyono, Hiroshi

NPJ vaccines

2023 Volume 8, Issue 1, Page(s) 106

Abstract: 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; ... ...

Abstract	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.
Language	English
Publishing date	2023-07-24
Publishing country	England
Document type	Journal Article
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-023-00700-3
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