Daily Respiratory Research Analysis
Analyzed 160 papers and selected 3 impactful papers.
Summary
Three standout studies advance respiratory science and practice: (1) immunopeptidome mapping in pulmonary fibrosis identifies MHC I–presented peptides and demonstrates a therapeutic vaccination concept, (2) influenza D virus replicates efficiently in human airway systems while dampening innate sensing, underscoring zoonotic potential, and (3) early postapproval safety surveillance of maternal RSVpreF vaccination finds no link to preterm birth but signals possible increases in hypertensive disorders and PROM that warrant further study.
Research Themes
- Antigen discovery and immunotherapy in pulmonary fibrosis
- Zoonotic risk and innate immune evasion of respiratory viruses
- Maternal vaccination safety and perinatal outcomes
Selected Articles
1. Immunopeptidome profiling in pulmonary fibrosis provides a platform for identifying therapeutic targets.
This study maps the MHC I immunopeptidome in human IPF explants and bleomycin mouse lungs, revealing fibrosis-associated peptides and computationally prioritizing targets. In vivo vaccination with selected peptides demonstrates a therapeutic concept, positioning epitope-directed immunotherapy as a potential anti-fibrotic strategy.
Impact: Introduces an antigen-focused therapeutic paradigm for pulmonary fibrosis with human–mouse translational evidence and in vivo vaccination proof-of-concept.
Clinical Implications: Provides a pipeline for epitope selection and therapeutic vaccination in fibrotic lung disease, potentially complementing or surpassing current anti-fibrotic drugs by targeting disease-specific antigen presentation.
Key Findings
- Defined the MHC class I immunopeptidomes from human IPF fibrotic foci and bleomycin-induced mouse lungs.
- Identified a diverse set of fibrosis-associated peptides and computationally prioritized therapeutic targets.
- Demonstrated in vivo feasibility of therapeutic vaccination using three prioritized peptides.
Methodological Strengths
- Human explant and murine model integration enabling translational relevance
- Mass spectrometry–based immunopeptidomics with cross-system validation
Limitations
- Abstract truncated; magnitude of therapeutic effect not fully detailed
- Preclinical validation limited to bleomycin model; external validation needed
Future Directions: Prospective validation of peptide vaccines in multiple fibrosis models; safety, immunogenicity, and efficacy studies toward early-phase clinical trials; exploration of combination with anti-fibrotic agents.
Fibrosis is a severe pathological outcome of many chronic diseases, yet the therapeutic potential of targeting the altered major histocompatibility complex (MHC) class I immunopeptidome remains largely unexplored. Here we characterized the MHC class I immunopeptidomes from both fibrotic foci of human idiopathic pulmonary fibrosis lung explants and bleomycin-treated mice, identifying a diverse repertoire of fibrosis-associated peptides. Parallel profiling of bleomycin-induced pulmonary fibrosis in mice enabled the computational prioritization of therapeutic targets. In vivo, therapeutic vaccination with three candidate peptides (MAF
2. Efficient replication of influenza D virus in the human airway underscores zoonotic potential.
Across human airway cell lines, primary cultures, and precision-cut lung slices, IDV replicated to titers comparable to influenza A virus while inducing weaker interferon signaling. Despite blunted innate sensing, IDV remained highly sensitive to interferon-primed antiviral states, emphasizing zoonotic potential and the importance of surveillance.
Impact: Provides mechanistic, multi-system evidence that IDV can efficiently infect human airway tissues with limited innate sensing, directly informing zoonotic risk assessment.
Clinical Implications: Supports heightened veterinary–human interface surveillance and inclusion of IDV in respiratory virus panels during unexplained outbreaks; informs antiviral readiness given interferon sensitivity.
Key Findings
- IDV achieved replication titers in human airway systems comparable to human influenza A virus.
- Innate immune sensing and interferon lambda 1/ISG induction were markedly lower with IDV than with IAV.
- Interferon pretreatment strongly restricted IDV replication, indicating sensitivity to established antiviral states.
- Similar infection kinetics were observed in porcine and human primary airway tissues.
Methodological Strengths
- Use of multiple human-relevant models (cell lines, primary ALI cultures, precision-cut lung slices)
- Comparative innate immune profiling against influenza A virus
Limitations
- In vitro/ex vivo systems without in vivo human infection data
- Limited number of isolates and time frame may not capture full strain diversity
Future Directions: Longitudinal animal–human interface surveillance, receptor tropism mapping, and in vivo pathogenicity studies; evaluation of prophylactic interferon strategies.
Influenza D virus (IDV), primarily found in livestock species, has demonstrated cross-species transmission potential, yet its threat to humans remains poorly understood. Here, we curated a panel of IDV isolates collected during field surveillance from 2011 to 2020 from swine and cattle to assess their ability to infect human airway cells as a proxy for zoonotic threat assessment. Using lung epithelial cell lines, primary well-differentiated airway epithelial cultures, and precision-cut lung slices, we demonstrated that IDV efficiently propagates in cells and tissues from the human respiratory tract, reaching titers comparable to human influenza A virus (IAV). Infection kinetics in primary porcine airway cultures and respiratory tissues mirrored those from humans, suggesting similar infectivity across species. To define host responses to IDV infection, we evaluated innate immune sensing and downstream interferon signaling in human respiratory cells. IDV infection resulted in markedly reduced activation of interferon regulatory factor signaling and diminished induction of interferon lambda 1 and interferon-stimulated genes compared to IAV, indicating inefficient activation of innate immune sensing pathways. However, IDV replication was potently restricted in interferon-pretreated cells, demonstrating sensitivity to interferon-mediated antiviral effector mechanisms once an antiviral state was established. Together, these findings show that IDV can efficiently infect the human airway while limiting innate immune sensing, a feature that may facilitate zoonotic spillover. Our study highlights the need for enhanced surveillance of IDV at the animal-human interface and provides a foundation for further investigation into its biology and potential for causing human infection and disease.
3. Sequential Safety Surveillance of RSVpreF Vaccination During Pregnancy Early in the Postapproval Period.
Among 13,619 RSVpreF-exposed pregnancies, there was no elevated risk of preterm birth vs concurrent (ARR 0.79; 95% CI 0.65-0.98) or historical comparators (ARR 0.87; 95% CI 0.78-0.96). Possible increased risks were detected for pregnancy-associated hypertensive disorders and PROM/preterm PROM in early surveillance, likely influenced by limited confounding control and uptake patterns.
Impact: Timely, large-scale safety signals for a newly approved maternal RSV vaccine inform obstetric counseling, surveillance priorities, and future pharmacoepidemiology.
Clinical Implications: Supports use of RSVpreF in pregnancy without increased preterm birth risk; clinicians should monitor for hypertensive disorders and membrane complications pending further adjusted analyses.
Key Findings
- 13,619 RSVpreF-exposed pregnancies analyzed across five sequential surveillance periods.
- No increased risk of preterm birth vs concurrent (ARR 0.79; 95% CI 0.65-0.98) or historical comparators (ARR 0.87; 95% CI 0.78-0.96).
- Elevated signals for pregnancy-associated hypertensive disorders (ARR 1.14–1.29) and PROM/preterm PROM (ARR up to 1.18) detected from the second surveillance period onward.
- No other increased risks observed among prespecified maternal or infant outcomes.
Methodological Strengths
- Sequential surveillance across multiple large health plans with concurrent and historical comparators
- Adjusted relative risk estimation for prespecified maternal and infant outcomes
Limitations
- Limited confounding control early in postlicensure uptake; potential residual bias
- Short surveillance window (first season) limits long-term safety inference
Future Directions: Extended multi-season analyses with enhanced confounder adjustment, subgroup stratification, and linkage to obstetric clinical data to refine risk estimates.
IMPORTANCE: Respiratory syncytial virus (RSV) is a leading cause of infant hospitalizations. In August 2023, the US Food and Drug Administration approved a bivalent RSV prefusion F subunit-based vaccine (RSVpreF) for maternal immunization to protect newborns. Sequential surveillance analysis provides information on the safety of a vaccine during its initial uptake. OBJECTIVE: To report the sequential surveillance findings for 10 prespecified safety outcomes of exposure to RSVpreF during pregnancy over the course of its first vaccination season in the US. DESIGN, SETTING, AND PARTICIPANTS: This cohort study with a sequential surveillance design used health plan data from 5 research partners. Health insurance data were analyzed across 5 sequential surveillance periods from April 25, 2024, through April 10, 2025. Pregnancies of individuals aged 15 to 54 years that culminated in a live birth or stillbirth and reached 32 gestational weeks were included. Cohorts included pregnancies exposed to RSVpreF (between September 22, 2023, and August 9, 2024); comparator pregnancies receiving influenza, COVID-19, and/or Tdap (tetanus, diphtheria, and acellular pertussis) vaccines but not the RSVpreF concurrently; and historical comparator pregnancies (vaccinated between September 1, 2018, and January 31, 2023). EXPOSURE: RSVpreF or comparator vaccines (influenza, COVID-19, and/or Tdap but not RSVpreF) between 32 through 36 weeks' gestation. MAIN OUTCOMES AND MEASURES: Primary outcomes were preterm birth and pregnancy-associated hypertensive disorders (composite of gestational hypertension; preeclampsia; eclampsia; hemolysis, elevated liver enzymes, and low platelet syndrome; or preexisting hypertension superimposed with preeclampsia or eclampsia). Secondary outcomes included premature rupture of membranes (PROM), preterm labor without preterm delivery, preterm PROM, maternal Guillan-Barré syndrome, and stillbirth. Infant outcomes were large for gestational age, small for gestational age, and low birth weight. Crude incidence proportions (IPs) and adjusted relative risks (ARR) were identified for these outcomes.