Publications by authors named "Yu Adachi"

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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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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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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The glass catfish is a freshwater fish with electroreceptors on its body surface. In this study, we investigated its behavioral response to sinusoidal electrical stimulation with a dipole wider than its body length and the spiking patterns of its electroreceptors. We observed that sinusoidal electric stimulation with a large dipole distance elicited in the glass catfish an avoidance movement whose frequency range is frequency-dependent.

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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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Administration in a lipid emulsion can modify the pharmacodynamics of drugs via a process known as lipid resuscitation. However, the detailed mechanism remains unclear. We studied the volume and another pharmacodynamic effect, the lipid sink, using propofol and thiamylal.

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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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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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  • The study investigated the impact of favipiravir treatment on neutralizing antibodies in patients recovering from moderate COVID-19.
  • It involved comparing 17 pairs of patients treated with favipiravir to a control group, focusing on the production and durability of antibodies against SARS-CoV-2 and its variants.
  • Findings revealed that favipiravir significantly sped up viral clearance and supported the development of effective neutralizing antibodies without hindering their effectiveness against different virus variants.
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  • The immune response to SARS-CoV-2 has become complex due to vaccinations and various infections, leading to diverse protective immunity in populations, especially with the emergence of the highly mutated Omicron variant.!* -
  • A study assessed how well different immune histories neutralized Omicron using blood samples from mRNA vaccinees and those with prior Alpha/Delta infections, finding that breakthrough infections enhanced neutralization against Omicron.!* -
  • Results showed that fully vaccinated individuals without breakthrough infections were less able to neutralize Omicron, while those with breakthrough infections produced stronger antibodies, emphasizing the importance of the vaccination-infection timing in determining immune response efficacy.!*
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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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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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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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Influenza viruses are a major public health problem. Vaccines are the best available countermeasure to induce effective immunity against infection with seasonal influenza viruses; however, the breadth of antibody responses in infection versus vaccination is quite different. Here, we show that nasal infection controls two sequential processes to induce neutralizing IgG antibodies recognizing the hemagglutinin (HA) of heterotypic strains.

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  • The Japanese government declared a state of emergency during the COVID-19 pandemic, urging citizens to adopt self-restraint behaviors like working from home and avoiding nightlife.
  • A study investigated the impact of changes in mobility across working, nightlife, and residential locations in major Japanese cities on the spread of COVID-19.
  • Results showed that reductions in nightlife mobility were particularly effective in mitigating COVID-19 outbreaks, highlighting regional differences in how these changes impacted each metropolitan area.
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  • Analysis of HLA-A, -C, -B, and -DRB1 genotypes in 178 Japanese COVID-19 patients found a significant link between the HLA-DRB1*09:01 allele and higher risk of severe illness.
  • The study reported an odds ratio of 3.62, showing that this specific allele increases susceptibility to severe COVID-19 even more than common preexisting conditions like hypertension and diabetes.
  • These findings suggest that genetic factors, specifically HLA alleles, may play a crucial role in determining the severity of COVID-19 in individuals.
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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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