Publications by authors named "Kiyoko Iwatsuki-Horimoto"

This study compared intestinal DNA phage dynamics and gut microbiota changes observed at the onset of coronavirus disease 2019 (COVID-19). The study participants included 19 healthy individuals and 19 patients with severe acute respiratory syndrome coronavirus 2 infection. Significant differences were observed in the diversity of the intestinal DNA virome after the onset of COVID-19 compared with that in healthy individuals.

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Highly pathogenic avian influenza (HPAI) H5 viruses from different clades have been circulating globally, threatening wild/domestic birds and mammals. Given frequent spillovers and high mortality among mammals, coupled with our inability to predict which clade of H5 virus has pandemic potential, cross-clade protective HPAI H5 vaccines are urgently needed. Here, we demonstrate the applicability of a lipid nanoparticle-based mRNA vaccine modality to induce cross-protective immunity against lethal HPAI virus infection.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 in China and rapidly spread worldwide, leading to a pandemic. The threat of SARS-CoV-2 is subsiding as most people have acquired sufficient antibodies through vaccination and/or infection to prevent severe COVID-19. After the emergence of the omicron variants, the seroprevalence of antibodies against the N protein elicited by SARS-CoV-2 infection ranged from 44.

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Article Synopsis
  • * After IVIg treatment, the patient's viral load decreased significantly, and there was no recurrence of symptoms.
  • * The findings suggest that combining IVIg with antiviral therapies may be an effective approach for treating relapsed COVID-19 in immunocompromised patients, particularly those who have undergone CD20 depleting therapy.
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Background: People living with HIV (PLWH) with chronic inflammation may have an increasing risk for coronavirus disease 2019 (COVID-19) severity; however, the impact of their gut microbiota on COVID-19 is not fully elucidated. Here, we analyzed the temporal changes in the gut microbiota composition of hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected PLWH (PLWH-CoV) and their correlation with COVID-19 severity.

Result: The 16S rRNA analysis results using stool samples (along the timeline from disease onset) from 12 hospitalized PLWH-CoV, whose median CD4 + T cell count was 671 cells/µl, were compared to those of 19 healthy people and 25 PLWH.

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Objective Prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been reported in immunocompromised patients, as they poorly develop antibodies against SARS-CoV-2. We conducted a clinical trial to determine the efficacy of Imdevimab/Casirivimab (Imde/Casiri), an anti-viral monoclonal antibody (mAb), for prolonged infection at our institution. Methods Nine patients with hematological malignancies (six with malignant lymphoma and three with multiple myeloma) in our institution presented with coronavirus disease 2019 caused by SARS-CoV-2 omicron variants (one, five, and one with BA.

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Here, we assessed the efficacy of a lipid nanoparticle-based mRNA vaccine candidate encoding the receptor-binding domain (LNP-mRNA-RBD) in mice. Mice immunized with LNP-mRNA-RBD based on the ancestral strain (ancestral-type LNP-mRNA-RBD) showed similar cellular responses against the ancestral strain and BA.5, but their neutralizing activity against BA.

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Cardiovascular disease is one of many risk factors that have been linked to increased severity or mortality in coronavirus disease 2019 (COVID-19) patients; however, the exact role of SARS-CoV-2 in the pathogenesis of cardiac inflammatory injury has not been established. A previous study reported that SARS-CoV-2 causes more severe disease with cardiomyopathy in a J2N-k animal model. Here, we investigated the sensitivity of J2N-k hamsters, as a cardiomyopathy animal model, to a delta strain of SARS-CoV-2 compared to J2N-n control animals.

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Article Synopsis
  • EG.5.1 is a new subvariant of the Omicron XBB variant of SARS-CoV-2 that is becoming more common globally, but its pathogenicity and immune evasion are still not well understood.
  • Research shows that EG.5.1 has similar growth ability and pathogenicity as XBB.1.5 in hamsters, but it spreads more effectively than the older BA.2 variant.
  • Additionally, plasma from recovered patients shows less neutralizing activity against EG.5.1 compared to XBB.1.5, suggesting that these differences might be contributing to its rise in prevalence among humans.
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The emergence and spread of new SARS-CoV-2 variants with mutations in the spike protein, such as the XBB.1.5 and XBB.

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Although SARS-CoV-2 evolution seeds a continuous stream of antibody-evasive viral variants, COVID-19 mRNA vaccines provide robust protection against severe disease and hospitalization. Here, we asked whether mRNA vaccine-induced memory T cells limit lung SARS-CoV-2 replication and severe disease. We show that mice and humans receiving booster BioNTech mRNA vaccine developed potent CD8 T cell responses and showed similar kinetics of expansion and contraction of granzyme B/perforin-expressing effector CD8 T cells.

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SARS-CoV-2 has gradually acquired amino acid substitutions in its S protein that reduce the potency of neutralizing antibodies, leading to decreased vaccine efficacy. Here, we attempted to obtain mutant viruses by passaging SARS-CoV-2 in the presence of plasma samples from convalescent patients or vaccinees to determine which amino acid substitutions affect the antigenicity of SARS-CoV-2. Several amino acid substitutions in the S2 region, as well as the N-terminal domain (NTD) and receptor-binding domain (RBD), affected the neutralization potency of plasma samples collected from vaccinees, indicating that amino acid substitutions in the S2 region as well as those in the NTD and RBD affect neutralization by vaccine-induced antibodies.

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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.

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Article Synopsis
  • SARS-CoV-2 has been circulating in humans since 2019 and has been reported in at least 32 animal species, including dogs and cats, which are particularly vulnerable to the virus.
  • A study developed an ELISA test to measure the prevalence of SARS-CoV-2 antibodies in dogs and cats by analyzing serum samples collected during two periods: early in the pandemic (May-June 2020) and mid-pandemic (October 2021 - January 2022).
  • Results showed low seroprevalence, with only a few samples testing positive for antibodies, indicating that dogs and cats in Japan are not a significant reservoir for SARS-CoV-2.
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Background: Like its predecessors in the XBB family, XBB.1.5 is highly immune evasive from therapeutic monoclonal antibodies and neutralizing antibodies generated by vaccination and/or infection.

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The prevalence of the Omicron subvariant BA.2.75 rapidly increased in India and Nepal during the summer of 2022, and spread globally.

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  • The study investigates the COVID-19 infection mechanisms by analyzing blood plasma from uninfected individuals and patients with mild and severe cases of SARS-CoV-2.
  • Severe patients displayed elevated levels of pulmonary surfactant, while mild cases showed increased levels of the enzyme CNDP1, suggesting different response mechanisms to the virus.
  • Elevated L-cystine and enzyme activity related to glutathione metabolism were observed in both groups, indicating potential roles for neutrophil extracellular traps (NETs) and CNDP1 in disease severity and immune response management.
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The influenza A(H1N1)pdm09 virus that emerged in 2009 causes seasonal epidemic worldwide. The virus acquired several amino acid substitutions that were responsible for antigenic drift until the 2018-2019 influenza season. Viruses possessing mutations in the NA and PA proteins that cause reduced susceptibility to NA inhibitors and baloxavir marboxil, respectively, have been detected after antiviral treatment, albeit infrequently.

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Objectives: The prolonged presence of infectious SARS-CoV-2 in deceased patients with COVID-19 has been reported. However, infectious virus titers have not been determined. Such information is important for public health, death investigation, and handling corpses.

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Although it has been 2.5 years since the coronavirus disease 2019 (COVID-19) pandemic began, the transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from a dead infected body remains unclear, and in Japan, bereaved family members are often not allowed to view in person a loved one who has died from COVID-19. In this study, we analyzed the possibility of SARS-CoV-2 transmission from a dead body using a hamster model.

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Synopsis of recent research by authors named "Kiyoko Iwatsuki-Horimoto"

  • - Kiyoko Iwatsuki-Horimoto's recent research focuses on the development and efficacy of vaccines and antiviral therapies against various strains of influenza and SARS-CoV-2, significantly contributing to the understanding of cross-protective immunity.
  • - The studies include the successful application of mRNA vaccine candidates in mice to combat different clades of highly pathogenic avian influenza and characterizations of SARS-CoV-2 Omicron variants, as well as the exploration of underlying mechanisms affecting COVID-19 severity in immunocompromised individuals.
  • - Findings indicate promising results for using combination therapies in treating persistent COVID-19 cases in immunocompromised patients, while also highlighting the role of gut microbiota in the pathogenesis of SARS-CoV-2 infection among people living with HIV.