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Article ; Online: [Competition between T Cells for a Finite Epidermal Niche Promotes Selective Retention of Antigen-specific Memory T Cells in the Epidermis].

Hirai, Toshiro

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan

2022 Volume 142, Issue 12, Page(s) 1327–1332

Abstract: Tissue-resident memory T cells are a highly abundant, non-blood circulating subset of memory T cells. These appear to be the most protective population of memory T cells at barrier surfaces. Long-term retention and survival of tissue-resident memory ... ...

Abstract	Tissue-resident memory T cells are a highly abundant, non-blood circulating subset of memory T cells. These appear to be the most protective population of memory T cells at barrier surfaces. Long-term retention and survival of tissue-resident memory CD8
MeSH term(s)	CD8-Positive T-Lymphocytes ; Memory T Cells ; Epidermal Cells ; Epidermis ; Transforming Growth Factor beta
Chemical Substances	Transforming Growth Factor beta
Language	Japanese
Publishing date	2022-12-01
Publishing country	Japan
Document type	English Abstract ; Journal Article
ZDB-ID	200514-1
ISSN	1347-5231 ; 0031-6903 ; 0372-7750 ; 0919-2085 ; 0919-2131
ISSN (online)	1347-5231
ISSN	0031-6903 ; 0372-7750 ; 0919-2085 ; 0919-2131
DOI	10.1248/yakushi.22-00155
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Article ; Online: Considerations of CD8

Hirai, Toshiro / Yoshioka, Yasuo

Frontiers in immunology

2022 Volume 13, Page(s) 918611

Abstract: The primary goal of vaccines that protect against respiratory viruses appears to be the induction of neutralizing antibodies for a long period. Although this goal need not be changed, recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ... ...

Abstract	The primary goal of vaccines that protect against respiratory viruses appears to be the induction of neutralizing antibodies for a long period. Although this goal need not be changed, recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have drawn strong attention to another arm of acquired immunity, CD8
MeSH term(s)	Antibodies, Neutralizing ; CD8-Positive T-Lymphocytes ; COVID-19/prevention & control ; Humans ; SARS-CoV-2 ; Viral Vaccines
Chemical Substances	Antibodies, Neutralizing ; Viral Vaccines
Language	English
Publishing date	2022-06-15
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.918611
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Article ; Online: Non-glycosylated G protein with CpG ODN provides robust protection against respiratory syncytial virus without inducing eosinophilia.

Kawahara, Eigo / Shibata, Takehiko / Hirai, Toshiro / Yoshioka, Yasuo

Frontiers in immunology

2023 Volume 14, Page(s) 1282016

Abstract: Introduction: Respiratory syncytial virus (RSV) vaccines targeting the fusion glycoprotein (F protein) are highly effective clinically in preventing RSV challenges. The attachment glycoprotein (G protein) is a potentially effective vaccine antigen ... ...

Abstract	Introduction: Respiratory syncytial virus (RSV) vaccines targeting the fusion glycoprotein (F protein) are highly effective clinically in preventing RSV challenges. The attachment glycoprotein (G protein) is a potentially effective vaccine antigen candidate, as it is important for cell adhesion during infection. However, vaccine-associated enhanced diseases in mice, such as eosinophilic lung inflammation following RSV challenge, are a concern with G protein vaccines. This study aimed to design an effective G protein vaccine with enhanced safety and efficacy by evaluating the efficacy and adverse reactions of vaccines composed of different recombinant G proteins and adjuvants in mice. Methods: Mice were subcutaneously immunized with glycosylated G protein expressed in mammalian cells (mG), non-glycosylated G protein expressed in Results: mG with any adjuvant was ineffective at inducing G-specific antibodies and had difficulty achieving both protection against RSV challenge and eosinophilia suppression. In particular, mG+CpG ODN induced G-specific T helper 1 (Th1) cells but only a few G-specific antibodies and did not protect against RSV challenge. However, eG+CpG ODN induced high levels of G-specific antibodies and Th1 cells and protected against RSV challenge without inducing pulmonary inflammation. Moreover, the combination vaccine of eG+F+CpG ODN showed greater protection against upper respiratory tract RSV challenge than using each single antigen vaccine alone. Discussion: These results indicate that the efficacy of recombinant G protein vaccines can be enhanced without inducing adverse reactions by using appropriate antigens and adjuvants, and their efficacy is further enhanced in the combination vaccine with F protein. These data provide valuable information for the clinical application of G protein vaccines.
MeSH term(s)	Mice ; Animals ; Respiratory Syncytial Virus Infections ; Antibodies, Viral ; Viral Fusion Proteins ; Respiratory Syncytial Virus, Human ; Pneumonia ; Adjuvants, Immunologic ; Recombinant Proteins ; Eosinophilia/prevention & control ; Vaccines ; GTP-Binding Proteins ; Oligodeoxyribonucleotides ; Glycoproteins ; Vaccines, Combined ; Mammals
Chemical Substances	Antibodies, Viral ; Viral Fusion Proteins ; Adjuvants, Immunologic ; Recombinant Proteins ; Vaccines ; GTP-Binding Proteins (EC 3.6.1.-) ; Oligodeoxyribonucleotides ; Glycoproteins ; Vaccines, Combined
Language	English
Publishing date	2023-12-19
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1282016
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Article ; Online: Adjuvant-free parenterally injectable vaccine platform that harnesses previously induced IgG as an antigen delivery carrier.

Kawai, Atsushi / Hirata, Haruki / Tokunoh, Nagisa / Ono, Chikako / Matsuura, Yoshiharu / Hirai, Toshiro / Yoshioka, Yasuo

Biochemical and biophysical research communications

2024 Volume 711, Page(s) 149919

Abstract: Subunit vaccines are among the most useful vaccine modalities; however, their low immunogenicity necessitates the addition of adjuvants. Although adjuvants improve immune responses induced by vaccines, they often cause adverse reactions. To address this, ...

Abstract	Subunit vaccines are among the most useful vaccine modalities; however, their low immunogenicity necessitates the addition of adjuvants. Although adjuvants improve immune responses induced by vaccines, they often cause adverse reactions. To address this, we developed an adjuvant-free subunit vaccine platform that uses pre-existing antibodies generated from past infections or vaccinations as carriers for the delivery of vaccine antigens. Although we have confirmed the usefulness of this platform for nasal vaccines, its suitability as a parenterally injectable vaccine remains uncertain. Here, we verified the potential of our vaccine platform to harness pre-existing immunity for parenterally injectable vaccines. We generated RBD-HA by combining the receptor binding domain (RBD) derived from SARS-CoV-2 as a vaccine antigen with hemagglutinin (HA) sourced from influenza viruses to serve as the carrier protein. We revealed that subcutaneous vaccination with RBD-HA effectively triggered strong RBD-specific IgG responses in mice previously infected with the influenza A virus, even in the absence of adjuvants, and conferred protection to mice against SARS-CoV-2 upon challenge. Furthermore, we revealed that vaccination with RBD-HA did not induce an inflammatory response, such as inflammatory cytokine production, swelling, and recruitment of inflammatory immune cells, whereas conventional vaccines combined with adjuvants induced these adverse reactions. In addition, we demonstrated the remarkable versatility of this platform using a vaccine antigen derived from Streptococcus pneumoniae. These findings indicate the potential of this adjuvant-free vaccine platform to enhance the efficacy of parenterally injectable subunit vaccines and reduce adverse reactions.
MeSH term(s)	Animals ; Immunoglobulin G/immunology ; Immunoglobulin G/blood ; Mice ; SARS-CoV-2/immunology ; COVID-19/prevention & control ; COVID-19/immunology ; COVID-19 Vaccines/immunology ; COVID-19 Vaccines/administration & dosage ; Mice, Inbred BALB C ; Female ; Hemagglutinin Glycoproteins, Influenza Virus/immunology ; Hemagglutinin Glycoproteins, Influenza Virus/administration & dosage ; Humans ; Antibodies, Viral/immunology ; Spike Glycoprotein, Coronavirus/immunology ; Vaccines, Subunit/immunology ; Vaccines, Subunit/administration & dosage ; Adjuvants, Immunologic/administration & dosage ; Influenza A virus/immunology ; Influenza Vaccines/immunology ; Influenza Vaccines/administration & dosage
Chemical Substances	Immunoglobulin G ; COVID-19 Vaccines ; Hemagglutinin Glycoproteins, Influenza Virus ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus ; Vaccines, Subunit ; Adjuvants, Immunologic ; spike protein, SARS-CoV-2 ; Influenza Vaccines
Language	English
Publishing date	2024-04-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2024.149919
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Zs.A 116: 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)

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Article ; Online: An inactivated whole-virion vaccine for Enterovirus D68 adjuvanted with CpG ODN or AddaVax elicits potent protective immunity in mice.

Senpuku, Kota / Kataoka-Nakamura, Chikako / Kunishima, Yuta / Hirai, Toshiro / Yoshioka, Yasuo

Vaccine

2024 Volume 42, Issue 9, Page(s) 2463–2474

Abstract: Enterovirus D68 (EV-D68), a pathogen that causes respiratory symptoms, mainly in children, has been implicated in acute flaccid myelitis, which is a poliomyelitis-like paralysis. Currently, there are no licensed vaccines or treatments for EV-D68 ... ...

Abstract	Enterovirus D68 (EV-D68), a pathogen that causes respiratory symptoms, mainly in children, has been implicated in acute flaccid myelitis, which is a poliomyelitis-like paralysis. Currently, there are no licensed vaccines or treatments for EV-D68 infections. Here, we investigated the optimal viral inactivation reagents, vaccine adjuvants, and route of vaccination in mice to optimize an inactivated whole-virion (WV) vaccine against EV-D68. We used formalin, β-propiolactone (BPL), and hydrogen peroxide as viral inactivation reagents and compared their effects on antibody responses. Use of any of these three viral inactivation reagents effectively induced neutralizing antibodies. Moreover, the antibody response induced by the BPL-inactivated WV vaccine was enhanced when adjuvanted with cytosine phosphoguanine oligodeoxynucleotide (CpG ODN) or AddaVax (MF59-like adjuvant), but not with aluminum hydroxide (alum). Consistent with the antibody response results, the protective effect of the inactivated WV vaccine against the EV-D68 challenge was enhanced when adjuvanted with CpG ODN or AddaVax, but not with alum. Further, while the intranasal inactivated WV vaccine induced EV-D68-specific IgA antibodies in the respiratory tract, it was less protective against EV-D68 challenge than the injectable vaccine. Thus, an injectable inactivated EV-D68 WV vaccine prepared with appropriate viral inactivation reagents and an optimal adjuvant is a promising EV-D68 vaccine.
MeSH term(s)	Humans ; Child ; Animals ; Mice ; Enterovirus D, Human ; Antibodies, Viral ; Vaccines, Inactivated ; Oligodeoxyribonucleotides ; Adjuvants, Immunologic ; Enterovirus Infections ; Alum Compounds ; Polysorbates ; Squalene
Chemical Substances	aluminum sulfate (34S289N54E) ; Addavax ; Antibodies, Viral ; Vaccines, Inactivated ; Oligodeoxyribonucleotides ; Adjuvants, Immunologic ; Alum Compounds ; Polysorbates ; Squalene (7QWM220FJH)
Language	English
Publishing date	2024-03-11
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2024.03.016
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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: CpG ODN enhances the efficacy of F protein vaccine against respiratory syncytial virus infection in the upper respiratory tract via CD4

Kawahara, Eigo / Yamamoto, Shinya / Shibata, Takehiko / Hirai, Toshiro / Yoshioka, Yasuo

Biochemical and biophysical research communications

2023 Volume 686, Page(s) 149143

Abstract: Respiratory syncytial virus (RSV) is a leading cause of severe respiratory illness worldwide, particularly in infants and older adults. Vaccines targeting the fusion glycoprotein (F protein) -one of the surface antigens of RSV- are highly effective in ... ...

Abstract	Respiratory syncytial virus (RSV) is a leading cause of severe respiratory illness worldwide, particularly in infants and older adults. Vaccines targeting the fusion glycoprotein (F protein) -one of the surface antigens of RSV- are highly effective in preventing RSV-associated severe lower respiratory tract disease. However, the efficacy of these vaccines against upper respiratory tract challenge needs improvement. Here, we aimed to examine the efficacy of F protein vaccines with or without CpG oligodeoxynucleotide (CpG ODN) as an adjuvant in the upper and lower respiratory tracts in mice. F + CpG ODN induced higher levels of F-specific IgG than that induced by F alone; however, levels of neutralizing antibodies did not increase compared to those induced by F alone. F + CpG ODN induced T helper 1 (Th1) cells while F alone induced T helper 2 (Th2) cells. Moreover, F + CpG ODN improved the protection against RSV challenge in the upper respiratory tract compared to F alone, which was largely dependent on CD4
MeSH term(s)	Mice ; Humans ; Animals ; Aged ; Respiratory Syncytial Virus Infections/prevention & control ; Antibodies, Viral ; Respiratory Syncytial Virus, Human ; Antibodies, Neutralizing ; Th1 Cells ; Vaccines ; Nose ; Oligodeoxyribonucleotides ; Mice, Inbred BALB C
Chemical Substances	Antibodies, Viral ; Antibodies, Neutralizing ; Vaccines ; Oligodeoxyribonucleotides
Language	English
Publishing date	2023-10-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2023.149143
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Zs.A 116: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Migration and Function of Memory CD8

Hirai, Toshiro / Whitley, Sarah K / Kaplan, Daniel H

The Journal of investigative dermatology

2019 Volume 140, Issue 4, Page(s) 748–755

Abstract: ... ...

Abstract	CD8
MeSH term(s)	Animals ; CD8-Positive T-Lymphocytes/immunology ; Humans ; Immunity, Cellular ; Immunologic Memory/immunology ; Skin/immunology
Language	English
Publishing date	2019-12-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2019.09.014
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Ui VI Zs.124: Show issues

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Article ; Online: Synergistic effect of non-neutralizing antibodies and interferon-γ for cross-protection against influenza.

Shibuya, Meito / Tamiya, Shigeyuki / Kawai, Atsushi / Hirai, Toshiro / Cragg, Mark S / Yoshioka, Yasuo

iScience

2021 Volume 24, Issue 10, Page(s) 103131

Abstract: Current influenza vaccines do not typically confer cross-protection against antigenically mismatched strains. To develop vaccines conferring broader cross-protection, recent evidence indicates the crucial role of both cross-reactive antibodies and viral- ... ...

Abstract	Current influenza vaccines do not typically confer cross-protection against antigenically mismatched strains. To develop vaccines conferring broader cross-protection, recent evidence indicates the crucial role of both cross-reactive antibodies and viral-specific CD4
Language	English
Publishing date	2021-09-15
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2021.103131
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Article ; Online: Keratinocyte-derived TGFβ is not required to maintain skin immune homeostasis.

Yang, Yi / Zenke, Yukari / Hirai, Toshiro / Kaplan, Daniel H

Journal of dermatological science

2019 Volume 94, Issue 2, Page(s) 290–297

Abstract: Background: Transforming growth factor beta 1 (TGFβ) is known to be a regulator of autoimmunity. Loss of TGFβ leads to severe multi-organ autoimmunity in mice. In skin, role of TGFβ in suppressing autoimmunity is unclear.: Objective: Determine ... ...

Abstract	Background: Transforming growth factor beta 1 (TGFβ) is known to be a regulator of autoimmunity. Loss of TGFβ leads to severe multi-organ autoimmunity in mice. In skin, role of TGFβ in suppressing autoimmunity is unclear. Objective: Determine whether Keratinocyte (KC)-derived TGFβ is required for skin immune homeostasis. Methods: We generated K14-CreER Results: KC was the major source of TGFβ in epidermis. Topical tamoxifen application led to efficient TGFβ1 deletion. The expected acanthosis was observed but no inflammatory infiltrate or altered numbers of resident immune cells were evident. Similarly, Itgb6 Conclusions: KC-derived TGFβ and epidermal TGFβ activation are not required to suppress skin autoimmunity in steady state.
MeSH term(s)	Animals ; Autoimmunity ; Gene Knockout Techniques ; Keratinocytes/immunology ; Keratinocytes/metabolism ; Mice ; Mice, Knockout ; Models, Animal ; Skin/cytology ; Skin/immunology ; Skin/metabolism ; Tamoxifen/pharmacology ; Transforming Growth Factor beta1/genetics ; Transforming Growth Factor beta1/immunology ; Transforming Growth Factor beta1/metabolism
Chemical Substances	Tgfb1 protein, mouse ; Transforming Growth Factor beta1 ; Tamoxifen (094ZI81Y45)
Language	English
Publishing date	2019-05-07
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1024446-3
ISSN	1873-569X ; 0923-1811
ISSN (online)	1873-569X
ISSN	0923-1811
DOI	10.1016/j.jdermsci.2019.04.008
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Zs.A 2870: Show issues

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Article ; Online: Intranasal immunization with an RBD-hemagglutinin fusion protein harnesses preexisting immunity to enhance antigen-specific responses.

Kawai, Atsushi / Tokunoh, Nagisa / Kawahara, Eigo / Tamiya, Shigeyuki / Okamura, Shinya / Ono, Chikako / Anindita, Jessica / Tanaka, Hiroki / Akita, Hidetaka / Yamasaki, Sho / Kunisawa, Jun / Okamoto, Toru / Matsuura, Yoshiharu / Hirai, Toshiro / Yoshioka, Yasuo

The Journal of clinical investigation

2023 Volume 133, Issue 23

Abstract: Intranasal vaccines are anticipated to be powerful tools for combating many infectious diseases, including SARS-CoV-2, because they induce not only systemic immunity but also mucosal immunity at the site of initial infection. However, they are generally ... ...

Abstract	Intranasal vaccines are anticipated to be powerful tools for combating many infectious diseases, including SARS-CoV-2, because they induce not only systemic immunity but also mucosal immunity at the site of initial infection. However, they are generally inefficient in inducing an antigen-specific immune response without adjuvants. Here, we developed an adjuvant-free intranasal vaccine platform that utilizes the preexisting immunity induced by previous infection or vaccination to enhance vaccine effectiveness. We made RBD-HA, a fusion of the receptor-binding domain (RBD) of spike derived from SARS-CoV-2 as a vaccine target with HA derived from influenza A virus (IAV) as a carrier protein. Intranasal immunization of previously IAV-infected mice with RBD-HA without an adjuvant elicited robust production of RBD-specific systemic IgG and mucosal IgA by utilizing both HA-specific preexisting IgG and CD4+ T cells. Consequently, the mice were efficiently protected from SARS-CoV-2 infection. Additionally, we demonstrated the high versatility of this intranasal vaccine platform by assessing various vaccine antigens and preexisting immunity associated with a variety of infectious diseases. The results of this study suggest the promising potential of this intranasal vaccine platform to address problems associated with intranasal vaccines.
MeSH term(s)	Animals ; Mice ; Hemagglutinins ; Influenza Vaccines ; Antibodies, Viral ; Immunization ; Vaccination ; Adjuvants, Immunologic/pharmacology ; Immunity, Mucosal ; Influenza A virus/genetics ; Immunoglobulin G ; Communicable Diseases
Chemical Substances	Hemagglutinins ; Influenza Vaccines ; Antibodies, Viral ; Adjuvants, Immunologic ; Immunoglobulin G
Language	English
Publishing date	2023-12-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI166827
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