Human norovirus is a leading cause of acute gastroenteritis worldwide across all age groups, yet no licensed vaccine is available. The major capsid protein, VP1, self-assembles into highly immunogenic virus-like particles (VLPs) that have shown promise in clinical studies. Recently, mRNA has emerged as a compelling platform for norovirus vaccination. However, whether VP1-encoding mRNA can drive authentic VLP formation in human cells relevant to the vaccination environment has remained unknown. In this study, we used multiple human cell lines, including THP-1-derived macrophage-like cells, to model the post-vaccination environment. Transfection with norovirus GII.4 VP1 mRNA or lipid nanoparticle-formulated VP1 mRNA induced both intracellular and extracellular VP1 expression. Sucrose gradient purification and electron microscopy confirmed VLP assembly. These particles retained key antigenic and functional properties, including recognition by norovirus-specific antibodies in human serum and binding to histo-blood group antigens. Collectively, our findings provide direct evidence that VP1-encoding mRNA can generate structurally and functionally relevant norovirus VLPs in physiologically relevant human cell systems. These results strengthen the mechanistic rationale for mRNA-based norovirus vaccines and support their continued development.
Background The Vaccine Safety Datalink (VSD) detected a statistical signal for ischemic events (ischemic stroke or transient ischemic attack) following bivalent mRNA COVID-19 vaccination through prospective surveillance during 2022–2023. Although multiple studies from other surveillance systems and countries reported no increased risk, important methodological limitations remained. This U.S. study addressed those limitations by evaluating the ischemic stroke risk following bivalent mRNA COVID-19 vaccination, influenza vaccination, and their same-day coadministration using an event-dependent self-controlled case series (SCCS) design. Methods Study outcomes included first-ever ischemic stroke (primary outcome), first-in-1-year ischemic stroke (secondary outcome), and ischemic events (exploratory outcomes), identified using ICD-10-CM codes in inpatient and emergency department settings during September 1, 2022–March 31, 2023, among individuals aged ≥12 years across eight VSD sites. Analyses were conducted separately for Pfizer-BioNTech and Moderna bivalent vaccines, with relative incidences (RI) and 95% confidence intervals (CI) estimated for 1–21-day and 1–42-day risk intervals, using person-time outside these intervals as the control period. Subgroup analyses were performed by age group (12–64, ≥65 years) and history of documented SARS-CoV-2 infection. Results A total of 6510 first-ever ischemic strokes were identified among more than 6.8 million participants. Among recipients of Pfizer-BioNTech bivalent COVID-19 and influenza vaccines, no statistically significant increased risk of first-ever ischemic stroke was observed following bivalent COVID-19 vaccination (RI = 0.94; 95% CI: 0.63–1.41), influenza vaccination (RI = 0.95; 95% CI: 0.82–1.10), or same-day coadministration (RI = 1.15; 95% CI: 0.88–1.49) within 1–21-day risk intervals; findings were similar for 1–42-day intervals. Comparable null results were observed for Moderna vaccine and across all subgroups, secondary, and exploratory outcomes. Conclusion No increased risk of ischemic stroke was found following bivalent mRNA COVID-19 vaccination, influenza vaccination, or their coadministration in this multi-site SCCS study. These findings are consistent with previous studies and underscore the importance of continued vaccine safety monitoring.
Aim To cross-culturally adapt the Vaccine Trust Gauge (VTG) for the Brazilian context and evaluate its content validity, structural validity, internal consistency, and test–retest reliability among adolescents. Methods This methodological study involved the cross-cultural adaptation of the VTG and the evaluation of its content validity, structural validity, internal consistency, and test–retest reliability. Content validity was assessed by an expert committee. Pre-testing was conducted with adolescents to evaluate clarity and acceptability. Internal structure was examined using confirmatory factor analysis (CFA) with the weighted least squares mean and variance adjusted estimator for ordinal data. Reliability was assessed using McDonald's omega and test–retest analysis with the intraclass correlation coefficient (ICC). Results The Brazilian version demonstrated strong content validity (Content Validity Index = 0.90). Pre-testing indicated good comprehension following minor linguistic adjustments. CFA supported the three-factor model (trust, importance, recommendation), with excellent fit indices (CFI = 0.972; TLI = 0.962; RMSEA = 0.056; SRMR = 0.052). Internal consistency ranged from 0.70 to 0.89. Test–retest analysis showed moderate temporal stability (ICC = 0.74). Conclusion The Brazilian VTG provides initial evidence of validity and reliability for assessing vaccine trust among adolescents. The instrument may support monitoring of vaccine trust, inform targeted interventions, and guide public health strategies across diverse immunization contexts.
