Daily Respiratory Research Analysis
Analyzed 211 papers and selected 3 impactful papers.
Summary
Analyzed 211 papers and selected 3 impactful articles.
Selected Articles
1. Phase 2 Randomized Bivalent RSVpreF Maternal Vaccine Trial: Final Safety, Antibody Persistence and Efficacy.
In this randomized, placebo-controlled phase 2b trial, maternal RSVpreF vaccination generated robust neutralizing responses with efficient transplacental transfer (infant GMT ratios 10.9–13.6; transfer 1.39–1.83), and infant titers persisted for months (half-life 39–44 days). Exploratory analyses suggested protection against medically attended infant RSV lower respiratory tract illness through 180 days.
Impact: Provides high-quality randomized evidence that maternal RSVpreF vaccination yields durable infant neutralization and potential clinical protection, informing dosing, timing, and policy for preventing severe early-life RSV disease.
Clinical Implications: Supports maternal RSV immunization during late pregnancy to protect infants through the first 6 months of life; programs should consider timing (24–36 weeks), waning (39–44-day half-life), and local RSV seasonality.
Key Findings
- Neutralizing titers peaked 2 weeks post-vaccination; infant GMT ratios at delivery versus placebo were 10.9–13.6 with transplacental transfer ratios of 1.39–1.83.
- Infant neutralizing titers remained elevated through 6 months with an estimated half-life of 39–44 days.
- Exploratory efficacy against medically attended infant RSV lower respiratory tract illness through day 180 was 75% (95% CI: -11%, 94%).
Methodological Strengths
- Randomized, placebo-controlled phase 2b design with registration (NCT04032093)
- Robust immunogenicity endpoints with transplacental transfer and infant persistence analyses
Limitations
- Exploratory efficacy estimates had wide confidence intervals spanning zero
- Phase 2 sample size and limited geographies constrain precision and generalizability
Future Directions: Define optimal timing relative to gestational age and RSV season, assess durability beyond 6 months, and evaluate programmatic effectiveness across diverse settings.
BACKGROUND: This report summarizes the final results from a randomized, placebo-controlled, phase 2b trial evaluating safety, antibody persistence, and potential efficacy of a bivalent respiratory syncytial virus (RSV) prefusion F (RSVpreF) vaccine in pregnant individuals and their infants. METHODS: Maternal participants were randomized from 24-36 weeks gestation to receive RSVpreF (120 or 240 µg ± aluminum hydroxide) or placebo. RESULTS: This analysis included 579 pregnant individuals and 572 infants from 4 countries (Argentina, Chile, South Africa, United States); 462 maternal participants received RSVpreF. Adverse events in the month following vaccination (maternal) or birth (infant) were mostly anticipated events in pregnancy and the neonatal period, respectively. For all RSVpreF groups, combined RSV-A/-B 50% neutralizing titers peaked 2 weeks after vaccination. At delivery, geometric mean titer ratios between RSVpreF and placebo recipients' infants were 10.9-13.6. Transplacental transfer ratios (all groups) were 1.39-1.83. Neutralizing geometric mean titers remained higher in infants whose mothers received RSVpreF versus placebo through their first 6 months of life, with an estimated half-life of 39-44 days. In an exploratory analysis, observed efficacy (95% confidence interval) for the combined RSVpreF groups against medically attended and severe medically attended infant RSV lower respiratory tract illness through the first 180 days of life was 75% (-11%, 94%) and 83% (-48%, 99%), respectively. CONCLUSIONS: RSVpreF had a favorable safety profile and elicited robust neutralizing responses with efficient transplacental transfer. The potential to prevent infant RSV-associated lower respiratory tract illness was subsequently confirmed in the pivotal phase 3 efficacy trial. (NCT04032093).
2. Assessment of Timing for Influenza Vaccination among Older Adults in Japan: The VENUS Study.
Using a target trial emulation with cloning, censoring, and weighting across four seasons and >130,000 adults per year, vaccination timing effects varied by season for influenza outcomes. However, early vaccination consistently reduced all-cause mortality across seasons, suggesting prioritization of earlier vaccination in older adults despite potential seasonal trade-offs in influenza incidence.
Impact: Provides rigorous causal-inference evidence to guide vaccination timing policy in older adults, balancing waning immunity and epidemic variability while highlighting mortality benefits of early vaccination.
Clinical Implications: For older adults, default to early-season vaccination to reduce all-cause mortality, while monitoring local epidemic timing to fine-tune strategies for minimizing influenza incidence and hospitalizations.
Key Findings
- Target trial emulation across four seasons with 131,178–138,438 older adults per year compared seven timing strategies.
- Delayed vaccination minimized influenza incidence in some seasons (2017/2018 and 2018/2019) but not others.
- Early vaccination consistently reduced all-cause mortality across all seasons with risk ratios around 0.80–0.96 versus no vaccination.
Methodological Strengths
- Target trial emulation with cloning, censoring, and weighting to mitigate immortal time and confounding
- Large population-based cohorts across multiple seasons with standardized cumulative incidence
Limitations
- Observational design susceptible to residual confounding and misclassification
- Season-specific findings limit generalizability; vaccine product/formulation differences not fully disentangled
Future Directions: Prospective adaptive policies linking vaccine supply, epidemic forecasts, and personalized timing; evaluate booster strategies and high-dose/adjuvanted formulations’ timing.
OBJECTIVES: In Japan, seasonal influenza vaccination is recommended for older adults between October and mid-December; however, the optimal vaccination timing remains unclear owing to waning immunity and variable epidemic patterns. In this study, we aimed to assess the effectiveness of different vaccination strategies in reducing influenza-related outcomes in older adults. METHODS: Using data from the VENUS Study, we conducted a target trial emulation including adults aged ≥65 years across four influenza seasons (2016/2017, 2017/2018, 2018/2019, and 2019/2020). We applied a cloning, censoring, and weighting approach. Each individual was cloned and assigned to one of seven vaccination strategies at the start of October: no vaccination, vaccination during October, October-November, October-December, November, November-December, or December. Outcomes included influenza, influenza-related hospitalization, and all-cause mortality. Risk ratios (RRs) and risk differences (RDs), relative to no vaccination, were estimated at the end of March for each season based on standardized cumulative incidence. RESULTS: Annual cohorts included 131,178-138,438 individuals (median age: 76-78 years; male sex: 40.1-41.0%). The influenza incidences and RRs varied by season. Delayed vaccination was associated with the lowest influenza incidence in 2017/2018 and 2018/2019, but not in the other seasons. Influenza-related hospitalizations showed seasonal trends similar to those of influenza. In contrast, early vaccination strategies generally led to reduced all-cause mortality across all seasons. The RRs were 0.80-0.93, 0.80-0.95, 0.82-1.00, and 0.81-0.96 in the 2016/2017, 2017/2018, 2018/2019, and 2019/2020 seasons, respectively. The RDs were larger for mortality than for the influenza-related outcomes. CONCLUSIONS: The effectiveness of each timing strategy varied depending on the outcome and season. Although delayed vaccination was associated with a lower influenza incidence in some seasons, early vaccination generally reduced all-cause mortality.
3. The emergence of novel H3N8 and H3N3 avian influenza viruses in chickens during multi-province surveillance in China and their potential public health risk.
Multi-province surveillance identified novel reassortant H3N8 (Eurasian H3, North American N8, H9N2 internal genes) and H3N3 (H3 from H3N8 lineage, N3 from H10N3, H9N2 internal genes) viruses. Mammalian adaptation-associated substitutions were present, and an H3N8 strain infected mice without adaptation, replicating in the upper respiratory tract. Antigenically, these H3 viruses did not cross-react with H5/H7/H9 by HI, signaling preparedness gaps.
Impact: Combines genomic, antigenic, and in vivo data to reveal emergent H3 reassortants with mammalian features and upper-airway replication, informing risk assessment, surveillance, and candidate vaccine strain development.
Clinical Implications: While immediate bedside impact is limited, findings warrant intensified poultry surveillance, occupational exposure risk management, and preemptive vaccine/diagnostic preparedness against H3 lineages with spillover potential.
Key Findings
- Surveillance across 21 provinces found 69/737 H3-positive samples; one H3N8 and ten H3N3 isolates underwent whole-genome characterization.
- H3N8 was a triple-reassortant (Eurasian H3, North American N8, H9N2 internal genes); H3N3 had HA from the H3N8 lineage, NA from H10N3, and H9N2 internal genes.
- Mammalian adaptation-associated substitutions (e.g., PB2 L89V, I292V; PB1 H436Y) were present; an H3N8 virus infected mice without adaptation, replicating mainly in the upper respiratory tract.
- HI assays showed no cross-reactivity with H5, H7, or H9 AIVs, indicating antigenic distinctness.
Methodological Strengths
- Integrated whole-genome sequencing, phylogenetics, and reassortment analysis with antigenic HI assays
- In vivo mouse challenge demonstrating upper-airway replication without prior adaptation
Limitations
- Limited number of isolates and single-country sampling constrain generalizability
- No ferret transmission studies or human clinical correlation to quantify spillover risk
Future Directions: Expand geographic sampling and host range, assess transmissibility (e.g., ferret models), and accelerate candidate vaccine/diagnostic development targeting emergent H3 lineages.
The H3 subtype avian influenza virus (AIV) poses a substantial global public health threat due to its high host adaptability and ongoing evolution. The recent emergence of novel H3N8 and H3N3 AIVs associated with cross-species transmission underscores the urgent need for enhanced epidemiological surveillance. In this study, we conducted surveillance and characterization of H3 AIVs based on a total of 737 poultry samples collected across 21 Chinese provinces from November 2022 to December 2023. Of these, 69 (9.4%) tested positive for H3 AIV by RT-qPCR, and one H3N8 isolate and ten H3N3 isolates were obtained for whole-genome characterization. We performed whole-genome sequencing, phylogenetic analysis, reassortment inference, and evaluation of key amino acid substitutions, alongside antigenic characterization using hemagglutination inhibition (HI) assays and an in vivo mouse challenge experiment. The H3N8 isolate was identified as a triple-reassortant virus possessing the Eurasian avian H3 gene, the North American avian N8 gene, and H9N2-derived internal genes. The H3N3 isolates represented reassortant viruses that had acquired the HA gene from the novel H3N8 AIV lineage, the NA gene from H10N3 AIV, and internal genes from H9N2 AIV. All isolates exhibited HA cleavage sites characteristic of low pathogenic avian influenza viruses. Additionally, several amino acid substitutions previously associated with enhanced mammalian adaptation were identified, including L89V and I292V in PB2 and H436Y in PB1. In a BALB/c mouse challenge experiment, the representative H3N8 virus established infection without prior adaptation and replicated predominantly in the upper respiratory tract, with detectable viral RNA in respiratory tissues and limited extrapulmonary dissemination. Antigenic analysis revealed no cross-reactivity between the novel H3 AIVs and H5, H7, or H9 AIVs as measured by HI. Based on molecular and phylogenetic characterization, antigenic assessment, and preliminary mammalian infection data, our findings provide evidence suggesting a potential public health risk. We recommend intensified surveillance of H3 AIVs in poultry and accelerated vaccine development to curb viral spread and improve public health preparedness.