Publications by authors named "Yoshimasa Takahashi"

An outbreak of influenza A(H1N1)pdm09 viruses exhibiting cross-resistance to oseltamivir and peramivir occurred in Yokohama, Japan, in September 2024. Among 24 students in a class, 11 were diagnosed with influenza or influenza-like illness, and viruses harbouring the NA H275Y and HA Q210H substitutions were isolated from four. Deep sequencing analysis confirmed the clonal spread of these mutants.

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The pandemic outbreak of SARS-CoV-2 has threatened human health worldwide. Among protective immune reactions, T cell responses are diverse among individuals, which is related to the differences in severity. A T cell subset, regulatory T (Treg) cells, is crucial for limiting excessive immune responses.

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Retrons are bacterial genetic elements that encode a reverse transcriptase and, in combination with toxic effector proteins, can serve as antiphage defense systems. However, the mechanisms of action of most retron effectors, and how phages evade retrons, are not well understood. Here, we show that some phages can evade retrons and other defense systems by producing specific tRNAs.

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  • Since 2019, SARS-CoV-2 has mutated, leading to various pandemic and epidemic waves that involve changes in its spike protein, which is key for the virus's entry into cells.
  • Researchers studied the spike proteins from variants BA.2.86 and JN.1, discovering structures where ACE2 receptor binds to the spike protein in both up and down conformations.
  • Their findings suggest that the down-conformation of the receptor-binding domain (RBD) is an important intermediate state that helps facilitate the virus's entry, with specific mutations like K356T impacting infectivity and resistance to neutralizing antibodies.
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  • Emerging respiratory viruses like SARS-CoV-2 pose a global risk, prompting the need for new antiviral strategies, particularly through the use of gapmer antisense oligonucleotides (ASOs).
  • Researchers synthesized about 300 ASOs targeting different regions of the SARS-CoV-2 RNA and effectively identified ASO#41, which inhibited viral replication and reduced infection-related cell damage.
  • ASO#41 demonstrated strong antiviral activity against multiple variants of SARS-CoV-2 in lab models and showed promise in mice, indicating its potential as a targeted treatment approach for respiratory viruses.
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Immunological imprinting by ancestral SARS-CoV-2 strains is thought to impede the robust induction of Omicron-specific humoral responses by Omicron-based booster vaccines. Here, we analyzed the specificity and neutralization activity of memory B (B) cells after repeated BA.5 exposure in individuals previously imprinted by ancestral strain-based mRNA vaccines.

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  • Persistent inflammation in people living with HIV (PWH) may influence their immune response to SARS-CoV-2 infection differently than in HIV-uninfected individuals.
  • During a study, proinflammatory cytokine levels were measured in PWH, revealing no significant differences in cytokine levels across various COVID-19 severity levels, unlike in HIV-uninfected individuals where higher levels correlated with severe cases.
  • The findings indicate that PWH are in a heightened inflammatory state but exhibit distinct inflammatory responses to SARS-CoV-2 compared to the general population, possibly due to impairments in their immune cells and existing inflammation.
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The incidence of rabies in Thailand reached its peak in 2018 with 18 human deaths. Preexposure prophylaxis (PrEP) vaccination is thus recommended for high-risk populations. WHO has recently recommended that patients who are exposed to a suspected rabid animal and have already been immunized against rabies should receive a 1-site intradermal (ID) injection of 0.

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  • Escherichia coli O157 is a harmful strain that can lead to serious health issues like hemolytic-uremic syndrome, prompting research into phage-based detection methods for identifying infections.
  • The study details the creation of a specific phage, vB_Eco4M-7, that targets E. coli O157 with a 68-kb genome, demonstrating effective detection capabilities.
  • This phage successfully identifies all 53 clinical isolates of E. coli O157 while distinguishing them from other similar bacteria, indicating potential for broader applications in detecting and treating pathogenic bacteria.
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  • NMR (Nuclear Magnetic Resonance) is a crucial technique for determining the structures of organic compounds and has been recognized as an effective tool for quantitative analysis, specifically in the form of quantitative NMR (qNMR).
  • qNMR has been officially incorporated into the Japanese Pharmacopoeia and is utilized extensively in drug development due to its ability to analyze compounds requiring minimal quantities without needing a reference standard.
  • This method allows for effective detection of residual solvents and can serve as a viable alternative to traditional methods like Gas Chromatography (GC), indicating its potential for broader application in the pharmaceutical industry.
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  • * This study specifically compared the bactericidal effectiveness of various lytic enzymes, particularly highlighting T1-spanin, which demonstrated the strongest activity against multiple bacterial strains.
  • * A new phage-based technology was developed to deliver the T1-spanin gene into target bacteria, showing potential for creating innovative and effective antimicrobial treatments.
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  • The study evaluated the LC16m8 vaccine's safety and effectiveness against the monkeypox virus (MPXV) in 50 healthy adults over 168 days.
  • On day 28, the vaccine showed strong immunogenicity, with 72% to 88% seroconversion rates, although these rates declined by day 168.
  • Adverse events were common but mostly mild, and no serious safety issues or cases of monkeypox were reported during the study period.
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Osteoporotic vertebral fracture (OVF) is the most common type of osteoporotic fracture and is associated with immobility and mortality. Bone anabolic agents, such as abaloparatide (ABL), are usually administered to patients with OVF to prevent subsequent fractures. Although several studies have shown that bone anabolic agents promote healing of long bone fractures, there is little evidence of their healing effect on vertebral bone fractures.

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Influenza infection and vaccination impart strain-specific immunity that protects against neither seasonal antigenic variants nor the next pandemic. However, antibodies directed to conserved sites can confer broad protection. Here we identify and characterize a class of human antibodies that engage a previously undescribed, conserved epitope on the influenza hemagglutinin (HA) protein.

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Plasticity of influenza virus hemagglutinin (HA) conformation increases an opportunity to generate conserved non-native epitopes with unknown functionality. Here, we have performed an in-depth analysis of human monoclonal antibodies against a stem-helix region that is occluded in native prefusion yet exposed in postfusion HA. A stem-helix antibody, LAH31, provided IgG Fc-dependent cross-group protection by targeting a stem-helix kinked loop epitope, with a unique structure emerging in the postfusion state.

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  • SARS-CoV-2 Omicron subvariants have developed the ability to evade detection by certain antibodies that target their receptor-binding sites (RBS).
  • Researchers identified a key area, Y489, that is vulnerable to broadly neutralizing antibodies and revealed how multiple antibodies interact with both Y489 and F486, linking this to the emergence of resistant subvariants.
  • A newly designed antibody (NIV-10/FD03) effectively neutralized the XBB variant and shows promise for developing therapies resistant to viral evolution and escape mechanisms.
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Mpox virus (formerly monkeypox virus [MPXV]) is a neglected zoonotic pathogen that caused a worldwide outbreak in May 2022. Given the lack of an established therapy, the development of an anti-MPXV strategy is of vital importance. To identify drug targets for the development of anti-MPXV agents, we screened a chemical library using an MPXV infection cell assay and found that gemcitabine, trifluridine, and mycophenolic acid (MPA) inhibited MPXV propagation.

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  • SARS-CoV-2 nucleocapsid protein (NP) is crucial for COVID-19 diagnostic tests like PCR and antigen rapid diagnostic tests (Ag-RDTs).
  • Ag-RDTs are more user-friendly than PCR, allowing for easier point-of-care and self-testing to detect the virus.
  • The study identified two high-affinity antibodies targeting distinct sites on NP, improving the sensitivity and specificity of Ag-RDTs, showcasing the effectiveness of high-throughput antibody isolation methods for enhancing diagnostic tools.
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Development of a universal influenza vaccine that can provide robust and long-lasting protection against heterologous infections is a global public health priority. A variety of vaccine antigens are designed to increase the antigenicity of conserved epitopes to elicit cross-protective antibodies that often lack virus-neutralizing activity. Given the contribution of antibody effector functions to cross-protection, adjuvants need to be added to modulate antibody effector functions as well as to enhance antibody quantity.

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Severe acute respiratory syndrome coronavirus 2-neutralizing antibodies primarily target the spike receptor binding domain (RBD). However, B cell antigen receptors (BCRs) on RBD-binding memory B (B) cells have variation in the neutralizing activities. Here, by combining single B cell profiling with antibody functional assessment, we dissected the phenotype of B cell harboring the potently neutralizing antibodies in coronavirus disease 2019 (COVID-19)-convalescent individuals.

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  • - Several antibody therapeutics exist for SARS-CoV-2, but their effectiveness has decreased against emerging variants, prompting researchers to explore new antibodies obtained from recovered COVID-19 patients' B cells.
  • - From 172 antibodies created using the Wuhan strain and Gamma variant, six were effective against earlier strains, while five showed some ability to combat Omicron sub-strains, indicating a potential for broader neutralization.
  • - Testing one promising antibody in hamsters showed a significant reduction in lung viral levels, demonstrating its potential as an antiviral treatment and underscoring the need for effective initial screening in developing such therapies.
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  • A study evaluated how well the serum from individuals who had breakthrough infections with different SARS-CoV-2 variants could neutralize those variants, which is key for creating better COVID-19 booster vaccines.
  • The research used Bayesian hierarchical modeling to analyze the effects of the time period between vaccination and infection, finding that different variants require different durations (2-4 months) to achieve optimal immune response saturation.
  • The findings emphasize the need for longer vaccine dosage intervals (at least 4 months) to effectively enhance the immune response against various Omicron variants, regardless of their genetic differences from the original strain.
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The stimulation of local immunity by vaccination is desirable for controlling virus replication in the respiratory tract. However, the local immune stimulatory effects of adjuvanted vaccines administered through the non-mucosal route are poorly understood. Here, we clarify the mechanisms by which non-mucosal inoculation of adjuvants stimulates the plasmacytoid dendritic cell (pDC)-dependent immunoglobulin (Ig)A response in the lungs.

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  • The study analyzes the immunogenicity of mRNA vaccines like BNT162b2 and compares them with the S-268019-b spike protein booster, focusing on the antibody responses against SARS-CoV-2 variants.
  • Results indicate that the S-268019-b booster generates stronger and longer-lasting IgG titers and neutralizing activity against variants like Omicron BA.1 and BA.5 compared to the BNT162b2 booster, particularly in groups without systemic side effects.
  • High-dimensional immune profiling reveals specific immune changes, such as CD16 natural killer cell dynamics, that correlate with the enhanced antibody responses prompted by the S-268019-b booster, suggesting advantages of heterologous boosting in immune response durability and
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