Daily Respiratory Research Analysis

A major barrier in mucosal vaccine development is achieving localized immunity without systemic toxicity. Here we engineered NanoCF501, a nanoparticulate STING agonist formulated with a 2-ethyl-2-oxazoline polymer. As an adjuvant, NanoCF501 facilitates efficient mucus penetration and localized respiratory retention, minimizing systemic exposure as confirmed by pharmacokinetics in rats. In mice, intranasal co-administration of NanoCF501 (1/20th the systemic dose) with an antigen comprising multivalent fragments derived from different coronaviruses induced robust mucosal and systemic immunity, conferring protection against homologous/heterologous pan-β-coronaviruses. Single-cell transcriptomics reveals STING-dependent reprogramming of lung antigen-presenting cells, enhancing adaptive responses. Our results were further validated in non-human primates and were extended to licensed influenza vaccines, showing that NanoCF501 can be used to repurpose intramuscular antigens for mucosal delivery. By integrating nanoscale rational design with innate targeting, NanoCF501 establishes a universal adjuvant for next-generation vaccines, advancing nanomedicine for pandemic preparedness.

AIMS: Atrial fibrillation (AF) is a risk factor for respiratory syncytial virus (RSV)-related adverse cardiac events. This prespecified analysis of the DAN-RSV trial investigated RSVpreF vaccine effectiveness (VE) against respiratory and cardiovascular outcomes among older adults with and without AF. METHODS AND RESULTS: DAN-RSV was a pragmatic, open-label, individually randomized trial in Denmark during the 2024/2025 winter season. Adults ≥60 years were randomly assigned 1:1 to RSVpreF vaccine or no vaccine. Baseline and endpoint data were obtained from nationwide health registries. The primary endpoint was hospitalization for RSV-related respiratory tract disease, occurring 14 days after study visit until May 31, 2025. Prespecified respiratory and cardiovascular endpoints were assessed by AF status. Among 131,276 participants, 10,126 (7.7%) had a history of AF (mean age 73.2 ± 6.9 years, 30.4% female). AF participants had higher event rates compared with non-AF participants. RSVpreF vaccine lowered the incidence of the primary endpoint with no evidence of effect modification by AF status (AF: VE 80.6% (95%CI -84.7 to 99.6), no AF: VE 84.6% (95%CI 32.3 to 98.3), p-value for interaction >0.99). RSVpreF vaccine was further associated with a lower incidence of all-cause respiratory tract disease hospitalization (AF: VE 25.7% (95%CI -16.9 to 46.1), no AF: VE 13.0% (95%CI -3.3 to 27.8)) and RSV-related and overall cardio-respiratory disease hospitalization with no evidence of effect modification by AF status (p-value for interaction ≥0.45 for all). RSVpreF vaccine was not significantly associated with AF or stroke hospitalizations regardless of AF status (p-value for interaction≥0.34 for all). CONCLUSIONS: In older adults, RSVpreF vaccine was associated with a lower incidence of RSV-related and all-cause respiratory tract disease hospitalizations, as well as RSV-related and all-cause cardio-respiratory disease hospitalizations, with no evidence of effect modification by AF status. This prespecified analysis of a large, randomized trial examined whether an RSV vaccine reduces serious respiratory and cardiovascular hospitalizations in older adults with and without atrial fibrillation. In the DAN-RSV trial of 131,276 adults aged 60 years and older, including 10,126 (7.7%) individuals with atrial fibrillation, the RSVpreF vaccine reduced hospitalizations due to RSV-related respiratory and cardio-respiratory disease, with no evidence of effect modification by atrial fibrillation history.Individuals with atrial fibrillation experienced higher rates of respiratory and cardiovascular hospitalizations overall, and RSVpreF was associated with lower numbers needed to vaccinate in this higher-risk group. No significant associations were observed between RSVpreF vaccination and atrial fibrillation hospitalizations.

BACKGROUND: Less invasive surfactant administration (LISA) is increasingly used to treat respiratory distress syndrome (RDS) in preterm infants, but variation in treatment effects across clinical subgroups remains unclear. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials published between 2010 and 2024 in MEDLINE, EMBASE, and CENTRAL comparing LISA with INtubation-SURfactant-Extubation (INSURE) in preterm infants with RDS. Random-effects generalized linear mixed models estimated pooled odds ratios with 95% confidence intervals. Prespecified subgroup analyses evaluated gestational age, surfactant type, antenatal corticosteroid exposure, and sedation. RESULTS: Twenty-one trials including 2656 infants were analyzed. LISA was associated with lower odds of bronchopulmonary dysplasia, death, BPD or death, intubation or mechanical ventilation, and severe intraventricular hemorrhage. Greater benefits were observed in infants ≤ 34 weeks and those with higher antenatal steroid exposure. CONCLUSION: LISA improves key outcomes compared with INSURE and may provide greater benefits in specific clinical subgroups.