Publications by authors named "Taishi Onodera"

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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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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Article Synopsis
  • 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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  • 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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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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Article Synopsis
  • 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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  • - Peracetic acid (PAA) is an effective disinfectant against various pathogens, including different strains of SARS-CoV-2, but its action mechanism wasn't fully understood until now.
  • - Research shows that PAA not only suppressed infections from both the original Wuhan strain and its variants (Delta and Omicron) but also reduced overall viral load.
  • - The study revealed that PAA disrupts the interaction between the virus's spike protein and the ACE2 receptor by destabilizing the spike protein's structure, suggesting a strong disinfectant approach to combat SARS-CoV-2.
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Severe fever with thrombocytopenia syndrome (SFTS) is an infectious disease with a high case fatality rate caused by the SFTS virus, and currently there are no approved specific treatments. Neutralizing monoclonal antibodies (mAbs) against the virus could be a therapeutic agent in SFTS treatment, but their development has not sufficiently been carried out. In the present study, mouse and human mAbs exposed to the viral envelope proteins Gn and Gc (16 clones each) were characterized in vitro and in vivo by using recombinant proteins, cell culture with viruses, and an SFTS animal model with IFNAR mice.

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Determinants of memory T cell longevity following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remain unknown. In addition, phenotypes associated with memory T cell longevity, antibody titers, and disease severity are incompletely understood. Here, we longitudinally analyzed SARS-CoV-2-specific T cell and antibody responses of a unique cohort with similar numbers of mild, moderate, and severe coronavirus disease 2019 cases.

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Two doses of Pfizer/BioNTech BNT162b2 mRNA vaccine elicit robust severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies with frequent adverse events. Here, by applying a high-dimensional immune profiling on 92 vaccinees, we identify six vaccine-induced immune dynamics that correlate with the amounts of neutralizing antibodies, the severity of adverse events, or both. The early dynamics of natural killer (NK)/monocyte subsets (CD16 NK cells, CD56 NK cells, and non-classical monocytes), dendritic cell (DC) subsets (DC3s and CD11c Axl Siglec-6 [AS]-DCs), and NKT-like cells are revealed as the distinct cell correlates for neutralizing-antibody titers, severity of adverse events, and both, respectively.

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Effective vaccines are essential for the control of the coronavirus disease 2019 (COVID-19) pandemic. Currently developed vaccines inducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S)-antigen-specific neutralizing antibodies (NAbs) are effective, but the appearance of NAb-resistant S variant viruses is of great concern. A vaccine inducing S-independent or NAb-independent SARS-CoV-2 control may contribute to containment of these variants.

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Mucosal immunity plays a crucial role in controlling upper respiratory infections, including influenza. We established a quantitative ELISA to measure the amount of influenza virus-specific salivery IgA (sIgA) and salivary IgG (sIgG) antibodies using a standard antibody broadly reactive to the influenza A virus. We then analyzed saliva and serum samples from seven individuals infected with the A(H1N1)pdm09 influenza virus during the 2019-2020 flu seasons.

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Viral spike proteins play important roles in the viral entry process, facilitating attachment to cellular receptors and fusion of the viral envelope with the cell membrane. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds to the cellular receptor angiotensin converting enzyme-2 (ACE2) via its receptor-binding domain (RBD). The cysteine residue at position 488, consisting of a disulfide bridge with cysteine 480 is located in an important structural loop at ACE2-binding surface of RBD, and is highly conserved among SARS-related coronaviruses.

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Multiple SARS-CoV-2 variants have mutations in the spike receptor binding domain (RBD) with potential to evade neutralizing antibody. In particular, the Beta and Omicron variants escape from antibody neutralizing activity in those who received two doses of BNT162b2 mRNA vaccine. Nonetheless, boosting with a third vaccine dose or by breakthrough infection improves the overall breadth of the neutralizing antibodies, but the mechanism remains unclear.

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Adaptive immunity is a fundamental component in controlling COVID-19. In this process, follicular helper T (Tfh) cells are a subset of CD4+ T cells that mediate the production of protective antibodies; however, the SARS-CoV-2 epitopes activating Tfh cells are not well characterized. Here, we identified and crystallized TCRs of public circulating Tfh (cTfh) clonotypes that are expanded in patients who have recovered from mild symptoms.

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Broadly protective vaccines against SARS-related coronaviruses that may cause future outbreaks are urgently needed. The SARS-CoV-2 spike receptor-binding domain (RBD) comprises two regions, the core-RBD and the receptor-binding motif (RBM); the former is structurally conserved between SARS-CoV-2 and SARS-CoV. Here, in order to elicit humoral responses to the more conserved core-RBD, we introduced N-linked glycans onto RBM surfaces of the SARS-CoV-2 RBD and used them as immunogens in a mouse model.

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Potent neutralizing SARS-CoV-2 antibodies often target the spike protein receptor-binding site (RBS), but the variability of RBS epitopes hampers broad neutralization of multiple sarbecoviruses and drifted viruses. Here, using humanized mice, we identified an RBS antibody with a germline V gene that potently neutralized SARS-related coronaviruses, including SARS-CoV and SARS-CoV-2 variants. X-ray crystallography revealed coordinated recognition by the heavy chain of non-RBS conserved sites and the light chain of RBS with a binding angle mimicking the angiotensin-converting enzyme 2 (ACE2) receptor.

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Article Synopsis
  • Antibody levels against SARS-CoV-2 decrease over time, but their ability to neutralize the virus improves as the immune response matures.
  • A study of convalescent plasma showed that while total antibody levels declined, the potency of these antibodies against the original virus increased significantly.
  • Late-stage antibodies demonstrated better effectiveness against emerging variants like B.1.351 and P.1, indicating that even as overall antibody levels drop, protection against the virus may still be maintained.
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Host lipid metabolism and viral responses are intimately connected. However, the process by which the acquired immune systems adapts lipid metabolism to meet demands, and whether or not the metabolic rewiring confers a selective advantage to host immunity, remains unclear. Here we show that viral infection attenuates the expression of genes related to lipid metabolism in murine CD4 T cells, which in turn increases the expression of antiviral genes.

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HLA-A, -C, -B, and -DRB1 genotypes were analyzed in 178 Japanese COVID-19 patients to investigate the association of HLA with severe COVID-19. Analysis of 32 common HLA alleles at four loci revealed a significant association between HLA-DRB1*09:01 and severe COVID-19 (odds ratio [OR], 3.62; 95% CI, 1.

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  • An increase in myeloid cells is a key feature of severe COVID-19, but previous research focused mainly on Europe, where the mortality rates are higher compared to Japan.
  • A study of blood samples from Japanese COVID-19 patients showed that polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) increased in severe cases but not in milder cases, and this expansion was seen in survivors but not in those who did not survive.
  • The findings suggest that the presence of PMN-MDSCs correlates with higher levels of IL-8 and is linked to better clinical outcomes, indicating that this cell type may serve as a potential predictor for recovery in severe COVID-19 patients in Japan.
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Hepatitis B virus (HBV) infection is a major public health problem. Human hepatocytes are infected with HBV via binding between the preS1 region in the large envelope protein of HBV and sodium taurocholate cotransporting polypeptide. Although several monoclonal antibodies (MAbs) that recognize the receptor binding domain in preS1 and neutralize HBV infection have been isolated, details of neutralizing epitopes are not understood.

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Virus-like particles (VLPs) provide a well-established vaccine platform; however, the immunogenic properties acquired by VLP structure remain poorly understood. In this study, we showed that systemic vaccination with norovirus VLP recalls human IgA responses at higher magnitudes than IgG responses under a humanized mouse model that was established by introducing human PBMCs in severely immunodeficient mice. The recall responses elicited by VLP vaccines depended on VLP structure and the disruption of VLP attenuated recall responses, with a more profound reduction being observed in IgA responses.

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Viral glycoproteins are under constant immune surveillance by a host's adaptive immune responses. Antigenic variation including glycan introduction or removal is among the mechanisms viruses have evolved to escape host immunity. Understanding how glycosylation affects immunodominance on complex protein antigens may help decipher underlying B cell biology.

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Synopsis of recent research by authors named "Taishi Onodera"

  • - Taishi Onodera's recent research primarily focuses on understanding the immune response to SARS-CoV-2 and the effectiveness of various vaccines, particularly in the context of evolving variants like Omicron, as well as the role of memory B cells and T cells in generating durable immunity.
  • - Findings from studies indicate that repeated exposures to SARS-CoV-2 variants can alter the evolution of memory B cells towards contemporary strains, while intradermal rabies boosters show promise in enhancing antibody production, highlighting adaptive strategies to improve immunological responses.
  • - Onodera's work also addresses the challenges posed by antibody-resistant variants through the development and characterization of bispecific antibodies and improved methodologies for neutralizing antibody isolation, which could lead to better diagnostic and therapeutic options against SARS-CoV-2 and other viral infections.