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.
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFRetrons 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.
View Article and Find Full Text PDFImmunological 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.
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFA current challenge is the emergence of SARS-CoV-2 variants, such as BQ.1.1 and XBB.
View Article and Find Full Text PDFOsteoporotic 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.
View Article and Find Full Text PDFInfluenza 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.
View Article and Find Full Text PDFPlasticity 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.
View Article and Find Full Text PDFMpox 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.
View Article and Find Full Text PDFDevelopment 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.
View Article and Find Full Text PDFSevere 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.
View Article and Find Full Text PDFThe 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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