9 results on '"Uraki, Ryuta"'
Search Results
2. Foxp3+ CD4+ regulatory T cells control dendritic cells in inducing antigen-specific immunity to emerging SARS-CoV-2 antigens.
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Uraki, Ryuta, Imai, Masaki, Ito, Mutsumi, Shime, Hiroaki, Odanaka, Mizuyu, Okuda, Moe, Kawaoka, Yoshihiro, and Yamazaki, Sayuri
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REGULATORY T cells , *T cells , *SARS-CoV-2 , *DENDRITIC cells , *T helper cells , *IMMUNITY , *ANTIGENS , *SELF-efficacy - Abstract
Regulatory T (Treg) cells, which constitute about 5–10% of CD4+T cells expressing Foxp3 transcription factor and CD25(IL-2 receptor α chain), are key regulators in controlling immunological self-tolerance and various immune responses. However, how Treg cells control antigen-specific immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. In this study, we examined the effect of transient breakdown of the immunological tolerance induced by Treg-cell depletion on adaptive immune responses against administered SARS-CoV-2 antigen, spike protein 1 (S1). Notably, without the use of adjuvants, transient Treg-cell depletion in mice induced anti-S1 antibodies that neutralized authentic SARS-CoV-2, follicular helper T cell formation and S1-binding germinal center B cell responses, but prevented the onset of developing autoimmune diseases. To further clarify the mechanisms, we investigated maturation of dendritic cells (DCs), which is essential to initiate antigen-specific immunity. We found that the transient Treg-cell depletion resulted in maturation of both migratory and resident DCs in draining lymph nodes that captured S1-antigen. Moreover, we observed S1-specific CD4+ T cells and CD8+ T cells with interferon-γ production. Thus, captured S1 was successfully presented by DCs, including cross-presentation to CD8+ T cells. These data indicate that transient Treg-cell depletion in the absence of adjuvants induces maturation of antigen-presenting DCs and succeeds in generating antigen-specific humoral and cellular immunity against emerging SARS-CoV-2 antigens. Finally, we showed that SARS-CoV-2 antigen-specific immune responses induced by transient Treg-cell depletion in the absence of adjuvants were compatible with those induced with an effective adjuvant, polyriboinosinic:polyribocytidyl acid (poly IC) and that the combination of transient Treg-cell depletion with poly IC induced potent responses. These findings highlight the capacity for manipulating Treg cells to induce protective adaptive immunity to SARS-CoV-2 with activating antigen-presenting DCs, which may improve the efficacy of ongoing vaccine therapies and help enhance responses to emerging SARS-CoV-2 variants. Author summary: To challenge SARS-CoV-2 and emerging antigens, it is important to explore innovative approaches to induce effective adaptive immunity to SARS-CoV-2. To induce antigen-specific immunity, vaccines generally need adjuvants to activate dendritic cells (DCs) to present antigens to naïve T cells. In this study, we focused on regulatory T (Treg) cells, which play a key role in maintaining self-tolerance and suppress important immune responses, and found that transient Treg-cell depletion without adjuvants induced protective SARS-CoV-2 antigen-specific immunity. Upon transient Treg-cell depletion in mice, a single administration of SARS-CoV-2 spike protein 1 (S1) induced neutralizing antibodies against live SARS-CoV-2 and evaded the onset of autoimmune diseases. Transient Treg-cell depletion initiated maturation of S1-captured DCs in draining lymph nodes, which is a crucial step to initiate antigen-specific immunity. S1-specific CD4+ and CD8+T cells that produced interferon-γ were also induced. Furthermore, we showed that transient Treg-cell depletion induced antigen-specific immune responses similar to vaccination with an adjuvant and that the combination induced a heightened effect. Thus, transient breakdown of the immunological tolerance induced by Treg-cell manipulation stimulates an adaptive response by activating DCs, providing an innovative approach to the design of vaccines for SARS-CoV-2 and emerging variants. [ABSTRACT FROM AUTHOR]
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- 2021
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3. Efficacy of antivirals and bivalent mRNA vaccines against SARS-CoV-2 isolate CH.1.1.
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Uraki, Ryuta, Ito, Mutsumi, Kiso, Maki, Yamayoshi, Seiya, Iwatsuki-Horimoto, Kiyoko, Sakai-Tagawa, Yuko, Furusawa, Yuri, Imai, Masaki, Koga, Michiko, Yamamoto, Shinya, Adachi, Eisuke, Saito, Makoto, Tsutsumi, Takeya, Otani, Amato, Kashima, Yukie, Kikuchi, Tetsuhiro, Yotsuyanagi, Hiroshi, Suzuki, Yutaka, and Kawaoka, Yoshihiro
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COVID-19 vaccines , *ANTIVIRAL agents , *MESSENGER RNA - Published
- 2023
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4. Antiviral and bivalent vaccine efficacy against an omicron XBB.1.5 isolate.
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Uraki, Ryuta, Ito, Mutsumi, Kiso, Maki, Yamayoshi, Seiya, Iwatsuki-Horimoto, Kiyoko, Furusawa, Yuri, Sakai-Tagawa, Yuko, Imai, Masaki, Koga, Michiko, Yamamoto, Shinya, Adachi, Eisuke, Saito, Makoto, Tsutsumi, Takeya, Otani, Amato, Kikuchi, Tetsuhiro, Yotsuyanagi, Hiroshi, Halfmann, Peter J, Pekosz, Andrew, and Kawaoka, Yoshihiro
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VACCINE effectiveness , *SARS-CoV-2 Omicron variant - Published
- 2023
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5. Characterization of Omicron BA.4.6, XBB, and BQ.1.1 subvariants in hamsters.
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Halfmann, Peter J., Iwatsuki-Horimoto, Kiyoko, Kuroda, Makoto, Hirata, Yuichiro, Yamayoshi, Seiya, Iida, Shun, Uraki, Ryuta, Ito, Mutsumi, Ueki, Hiroshi, Furusawa, Yuri, Sakai-Tagawa, Yuko, Kiso, Maki, Armbrust, Tammy, Spyra, Sam, Maeda, Ken, Wang, Zhongde, Imai, Masaki, Suzuki, Tadaki, and Kawaoka, Yoshihiro
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SARS-CoV-2 Omicron variant , *GOLDEN hamster , *HAMSTERS , *BINDING site assay , *TURBINATE bones , *MORTALITY , *ANGIOTENSIN converting enzyme , *LUNGS - Abstract
During the Omicron wave, previous variants such as BA.2, BA.4, and BA.5 were replaced by newer variants with additional mutations in the spike protein. These variants, BA.4.6, BQ.1.1, and XBB, have spread in different countries with different degrees of success. Here, we evaluated the replicative ability and pathogenicity of BA.4.6, BQ1.1, and XBB clinical isolates in male Syrian hamsters. Although we found no substantial differences in weight change among hamsters infected with these Omicron subvariants, the replicative ability of BQ.1.1 and XBB in lung tissue was higher than that of BA.4.6 and BA.5. Of note, BQ.1.1 was lethal in both male and female transgenic human ACE2 hamsters. In competition assays, XBB replicated better than BQ.1.1 in the nasal turbinate tissues of female hamsters previously infected with Omicron BA.2. These results suggest that newer Omicron subvariants in the XBB family are still evolving and should be closely monitored. Omicron variants BQ.1.1 and XBB increased pathogenicity in wild-type hamsters, with BQ.1.1 showing higher mortality in human ACE2 transgenic hamsters compared to earlier Omicron variants.. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Research article antibody induction and immune response in nasal cavity by third dose of SARS-CoV-2 mRNA vaccination.
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Ishizaka, Aya, Koga, Michiko, Mizutani, Taketoshi, Uraki, Ryuta, Yamayoshi, Seiya, Iwatsuki-Horimoto, Kiyoko, Yamamoto, Shinya, Imai, Masaki, Tsutsumi, Takeya, Suzuki, Yutaka, Kawaoka, Yoshihiro, and Yotsuyanagi, Hiroshi
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NASAL cavity , *IMMUNE response , *SARS-CoV-2 , *NASAL mucosa , *MESSENGER RNA , *IMMUNOGLOBULINS - Abstract
Background: The mucosa serves as the first defence against pathogens and facilitates the surveillance and elimination of symbiotic bacteria by mucosal immunity. Recently, the mRNA vaccine against SARS-CoV-2 has been demonstrated to induce secretory antibodies in the oral and nasal cavities in addition to a systemic immune response. However, the mechanism of induced immune stimulation effect on mucosal immunity and commensal bacteria profile remains unclear. Methods: Here, we longitudinally analysed the changing nasal microbiota and both systemic and nasal immune response upon SARS-CoV-2 mRNA vaccination, and evaluated how mRNA vaccination influenced nasal microbiota in 18 healthy participants who had received the third BNT162b. Results: The nasal S-RBD IgG level correlated significantly with plasma IgG levels until 1 month and the levels were sustained for 3 months post-vaccination. In contrast, nasal S-RBD IgA induction peaked at 1 month, albeit slightly, and correlated only with plasma IgA, but the induction level decreased markedly at 3 months post-vaccination. 16 S rRNA sequencing of the nasal microbiota post-vaccination revealed not an overall change, but a decrease in certain opportunistic bacteria, mainly Fusobacterium. The decrease in these bacteria was more pronounced in those who exhibited nasal S-RBD IgA induction, and those with higher S-RBD IgA induction had lower relative amounts of potentially pathogenic bacteria such as Pseudomonas pre-vaccination. In addition, plasma and mucosal S-RBD IgG levels correlated with decreased commensal pathogens such as Finegoldia. Conclusions: These findings suggest that the third dose of SARS-CoV-2 mRNA vaccination induced S-RBD antibodies in the nasal mucosa and may have stimulated mucosal immunity against opportunistic bacterial pathogens. This effect, albeit probably secondary, may be considered one of the benefits of mRNA vaccination. Furthermore, our data suggest that a cooperative function of mucosal and systemic immunity in the reduction of bacteria and provides a better understanding of the symbiotic relationship between the host and bacteria in the nasal mucosa. [ABSTRACT FROM AUTHOR]
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- 2023
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7. Plasminogen activator inhibitor 1 is not a major causative factor for exacerbation in a mouse model of SARS-CoV-2 infection.
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Nakayama, Takashin, Azegami, Tatsuhiko, Kiso, Maki, Imai, Masaki, Uraki, Ryuta, Hayashi, Kaori, Hishikawa, Akihito, Yoshimoto, Norifumi, Nakamichi, Ran, Sugita-Nishimura, Erina, Yoshida-Hama, Eriko, Kawaoka, Yoshihiro, and Itoh, Hiroshi
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SARS-CoV-2 , *PLASMINOGEN activator inhibitors , *PLASMINOGEN , *WEIGHT loss , *COVID-19 , *LABORATORY mice - Abstract
Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global pandemic. Although several vaccines targeting SARS-CoV-2 spike proteins protect against COVID-19 infection, mutations affecting virus transmissibility and immune evasion potential have reduced their efficacy, leading to the need for a more efficient strategy. Available clinical evidence regarding COVID-19 suggests that endothelial dysfunction with thrombosis is a central pathogenesis of progression to systemic disease, in which overexpression of plasminogen activator inhibitor-1 (PAI-1) may be important. Here we developed a novel peptide vaccine against PAI-1 and evaluated its effect on lipopolysaccharide (LPS)-induced sepsis and SARS-CoV-2 infection in mice. Administration of LPS and mouse-adapted SARS-CoV-2 increased serum PAI-1 levels, although the latter showed smaller levels. In an LPS-induced sepsis model, mice immunized with PAI-1 vaccine showed reduced organ damage and microvascular thrombosis and improved survival compared with vehicle-treated mice. In plasma clot lysis assays, vaccination-induced serum IgG antibodies were fibrinolytic. However, in a SARS-CoV-2 infection model, survival and symptom severity (i.e., body weight reduction) did not differ between vaccine- and vehicle-treated groups. These results indicate that although PAI-1 may promote the severity of sepsis by increasing thrombus formation, it might not be a major contributor to COVID-19 exacerbation. [ABSTRACT FROM AUTHOR]
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- 2023
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8. In Vitro Efficacy of Antiviral Agents against Omicron Subvariant BA.4.6.
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Emi Takashita, Seiya Yamayoshi, Yoshihiro Kawaoka, Takashita, Emi, Yamayoshi, Seiya, Halfmann, Peter, Wilson, Nancy, Ries, Hunter, Richardson, Alex, Bobholz, Max, Vuyk, William, Maddox, Robert, Baker, David A, Friedrich, Thomas C, O'Connor, David H, Uraki, Ryuta, Ito, Mutsumi, Sakai-Tagawa, Yuko, Adachi, Eisuke, and Saito, Makoto
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ANTIVIRAL agents , *VIRAL antibodies , *PHARMACODYNAMICS - Abstract
The article informs about the BA.S subvariant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant has become dominant in most countries around the world. Topics incluyde the amino acid substitutions in the receptorbinding domain of the spike protein, which is the major target for vaccines and therapeutic monoclonal antibodies against SARS-CoV-2; and effectiveness of current vaccines and therapeutic monoclonal antibodies against this subvariant will be decreased.
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- 2022
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9. Efficacy of Antiviral Agents against the Omicron Subvariant BA.2.75.
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Emi Takashita, Selya Yarnayoshi, Yoshihiro Kawaoka, Takashita, Emi, Yamayoshi, Seiya, Fukushi, Shuetsu, Suzuki, Tadaki, Maeda, Ken, Sakai-Tagawa, Yuko, Ito, Mutsumi, Uraki, Ryuta, Halfmann, Peter, Watanabe, Shinji, Takeda, Makoto, Hasegawa, Hideki, Imai, Masaki, and Kawaoka, Yoshihiro
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IMMUNOGLOBULINS , *ANTIVIRAL agents , *RESEARCH funding , *VIRAL antibodies - Published
- 2022
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