Publications by authors named "Nagisa Tokunoh"

Intranasal vaccines potentially offer superior protection against viral infections compared with injectable vaccines. The immunogenicity of intranasal vaccines including adenovirus vector (AdV), has room for improvement, while few options are available for safe execution. In this study, we demonstrate that modifying a basic parameter of vaccine formulation, i.

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Coronavirus disease 2019 (COVID-19) induces respiratory dysfunction as well as kidney injury. Although the kidney is considered a target organ of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and affected by the COVID-19-induced cytokine storm, the mechanisms of renal reaction in SARS-CoV-2 infection are unknown. In this study, a murine COVID-19 model was induced by nasal infection with mouse-adapted SARS-CoV-2 (MA10).

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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.

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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.

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Article Synopsis
  • Vaccinations can lessen the severity of COVID-19, but SARS-CoV-2 remains a global health issue; nasal vaccines could be more effective at preventing infections in the upper respiratory tract compared to traditional injections.
  • A study showed that mice receiving the nasal vaccine mounted a stronger local immune response (higher IgA levels) in the nasal area compared to those receiving a subcutaneous vaccine, although systemic IgG levels were higher with the injection.
  • The research indicates that an intranasal inactivated whole-virion vaccine could be a promising approach for enhancing protection against COVID-19 infections, particularly in the upper respiratory tract.
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Direct administration of vaccines to mucosal surfaces, such as oral or nasal vaccination, represents an attractive alternative, or complement, to current parenteral vaccination because it has a potential to induce antigen-specific immunity both at mucosal and systemic tissues. Although bacterium-like particles (BLPs), peptidoglycan structures derived from lactic acid bacteria, have been investigated as a novel adjuvant for oral or nasal vaccines, it remains unclear whether the administration routes differ the adjuvant effect of BLPs. Here, we showed that the adjuvant effect of BLPs from NZ9000 is greater with the nasal administration than with the oral administration.

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Article Synopsis
  • There is an urgent need for new drugs to combat severe infectious diseases, such as COVID-19, as current treatments do not fully reduce mortality rates.
  • The study focuses on a protein called Robo4, which stabilizes endothelial cells and decreases vascular permeability, showing that increasing its expression may help reduce death rates in cases of severe infection.
  • Researchers found that a specific inhibitor could effectively boost Robo4 levels in the lungs and protect against both LPS-induced inflammation and SARS-CoV-2 infection, suggesting small molecules that enhance Robo4 could be promising therapeutic options.
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In the initial process of coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects respiratory epithelial cells and then transfers to other organs the blood vessels. It is believed that SARS-CoV-2 can pass the vascular wall by altering the endothelial barrier using an unknown mechanism. In this study, we investigated the effect of SARS-CoV-2 on the endothelial barrier using an airway-on-a-chip that mimics respiratory organs and found that SARS-CoV-2 produced from infected epithelial cells disrupts the barrier by decreasing Claudin-5 (CLDN5), a tight junction protein, and disrupting vascular endothelial cadherin-mediated adherens junctions.

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is a murine pathogenic bacterium that adheres to intestinal epithelial cells, resulting in loss of microvilli and pedestal formation, and alters multiple cellular processes, including actin dynamics. Translocated intimin receptor (Tir), one of its virulence factors, functions as receptor for intimin, a bacterial adhesin, thereby mediating bacterial adhesion to epithelial cells. Although robust immune responses are induced to eliminate pathogenic bacteria in the host, they are suppressed against harmless commensal bacteria.

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Over the past two decades, lactic acid bacteria (LAB) have been intensively studied as potential bacterial carriers for therapeutic materials, such as vaccine antigens, to the mucosal tissues. LAB have several attractive advantages as carriers of mucosal vaccines, and the effectiveness of LAB vaccines has been demonstrated in numerous studies. Research on LAB vaccines to date has focused on whether antigen-specific immunity, particularly antibody responses, can be induced.

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Evaluation of the efficacy of vaccine candidates that prevent enteropathogenic and enterohemorrhagic Escherichia coli (EPEC/EHEC) infection in mouse models is difficult due to their limited pathogenicity in mice. Citrobacter rodentium, a murine pathogenic bacterium that shares its infection strategy and virulence genes with EPEC/EHEC, has been used as a model pathogen to develop novel vaccine strategies or platforms for these bacteria. However, there are few reports on the comparative effectiveness of novel vaccine platforms as no C.

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