Daily Respiratory Research Analysis
Three impactful respiratory studies stood out: broadly cross-protective neuraminidase antibodies that neutralize seasonal and avian influenza (including H5N1/H7N9), a mechanistic IPF study identifying epithelial YAP-TEAD/LOX signaling as a therapeutic target reversible by verteporfin, and a cluster-randomized surveillance study showing ARI case definitions capture RSV better than ILI in older adults. Together, they advance vaccine/antibody strategies, antifibrotic targets, and public health surv
Summary
Three impactful respiratory studies stood out: broadly cross-protective neuraminidase antibodies that neutralize seasonal and avian influenza (including H5N1/H7N9), a mechanistic IPF study identifying epithelial YAP-TEAD/LOX signaling as a therapeutic target reversible by verteporfin, and a cluster-randomized surveillance study showing ARI case definitions capture RSV better than ILI in older adults. Together, they advance vaccine/antibody strategies, antifibrotic targets, and public health surveillance.
Research Themes
- Universal influenza immunity via neuraminidase-targeting antibodies
- Epithelial drivers of pulmonary fibrosis and antifibrotic repurposing
- Optimizing RSV surveillance: ARI vs ILI case definitions
Selected Articles
1. Broad neuraminidase antibodies confer protection against seasonal and avian influenza viruses.
Two human monoclonal antibodies (CAV-F6, CAV-F34) broadly inhibit neuraminidase activity, protect mice from seasonal influenza, and neutralize avian strains (H5N1, H7N9). Structural data show HCDR3 engagement of conserved active-site residues, informing NA-focused universal vaccine and therapeutic designs.
Impact: This work reveals broadly neutralizing NA antibodies with activity against zoonotic strains, a key step toward universal influenza interventions beyond HA-focused strategies.
Clinical Implications: Supports inclusion of NA antigens in next-generation influenza vaccines and development of NA-targeting therapeutics with potential pandemic utility.
Key Findings
- Identified two monoclonal antibodies (CAV-F6, CAV-F34) that inhibit NA across multiple influenza subtypes.
- Both antibodies protected female mice from seasonal influenza and neutralized avian H5N1 and H7N9 strains.
- Structural analyses showed HCDR3-mediated binding to conserved NA active-site regions, blocking sialic acid interaction.
Methodological Strengths
- Integration of enzymatic inhibition, in vivo protection studies, and high-resolution structural analysis.
- Cross-subtype assessment including zoonotic strains enhances translational relevance.
Limitations
- Protection demonstrated in mouse models; human efficacy remains to be established.
- Female mice were used for protection studies; sex-based differences were not fully explored.
Future Directions: Evaluate human prophylactic/therapeutic potential of NA bnAbs, define correlates of protection, and translate conserved NA epitopes into vaccine immunogen designs.
2. Inhibition of epithelial cell YAP-TEAD/LOX signaling attenuates pulmonary fibrosis in preclinical models.
Fibrotic AT2 cells drive matrix production and crosslinking through YAP-induced LOX. Pharmacologic YAP inhibition with verteporfin reverses AT2 reprogramming and LOX expression in murine fibrosis and human ex vivo tissue, nominating epithelial YAP-TEAD/LOX as a druggable IPF pathway.
Impact: Shifts focus to epithelial drivers of fibrosis and demonstrates reversibility via an approved photosensitizer (verteporfin), opening a tractable translational path.
Clinical Implications: Supports repurposing verteporfin and development of YAP-TEAD/LOX inhibitors targeting alveolar epithelium as potential disease-modifying therapies in IPF.
Key Findings
- Fibrotic alveolar type II cells upregulate LOX via YAP, increasing extracellular matrix crosslinking.
- Verteporfin-mediated YAP inhibition reverses AT2 reprogramming and reduces LOX expression in vivo and in human fibrotic tissue ex vivo.
- Identifies epithelial YAP-TEAD/LOX signaling as a therapeutic axis for IPF.
Methodological Strengths
- Use of complementary in vivo fibrosis models and ex vivo human fibrotic tissue.
- Mechanistic linkage from transcriptional coactivator (YAP) to enzymatic effector (LOX) with pharmacologic reversal.
Limitations
- Preclinical evidence without clinical efficacy data in IPF patients.
- Potential off-target or photodynamic effects of verteporfin require careful clinical evaluation.
Future Directions: Phase 1/2 trials of verteporfin or selective YAP-TEAD/LOX inhibitors in IPF, biomarker development (epithelial YAP/LOX signatures), and safety profiling.
3. A Cluster Randomized Study to Explore Case Definitions, Clinical Course and Consequences of RSV in Community-Dwelling Adults Aged ≥ 50 Years.
In a GP-level cluster randomization (n=1431), ARI-based case definitions captured more RSV than ILI. An ARI variant including wheeze/productive cough/rhonchi/dyspnea achieved 92% sensitivity (30.8% specificity). RSV outpatient burden was substantial with 30.7% complications, 2.7% hospitalizations, and notable societal costs.
Impact: Directly informs RSV surveillance and testing strategies in older adults by demonstrating the superiority of ARI-based definitions and proposing a high-sensitivity clinical qualifier set.
Clinical Implications: Public health programs should favor ARI-based triggers (with respiratory qualifiers) over ILI for RSV testing in adults ≥50 years to avoid under-ascertainment and to better allocate diagnostics and preventive measures.
Key Findings
- ARI case definitions detected more RSV than ILI (5.8% vs 4.6%; OR 1.26; 95% CI 0.60–2.65; higher OR after excluding low-enrolling GPs).
- An ARI variant with wheeze/productive cough/rhonchi/dyspnea achieved 92.0% sensitivity and 30.8% specificity for RSV.
- Among RSV-positive outpatients, 30.7% had complications, 2.7% were hospitalized, 1.3% died; mean societal cost per case up to €899.51.
Methodological Strengths
- Cluster randomization at the GP level with pathogen testing for all enrolled subjects.
- Prospective follow-up of RSV-positive patients capturing clinical outcomes and costs.
Limitations
- Primary ARI vs ILI comparison yielded wide CIs with non-significant OR; power limited by enrollment variability.
- Specificity of the high-sensitivity ARI variant was low (30.8%), which may increase testing burden.
Future Directions: Validate refined ARI qualifiers in larger multicountry cohorts, integrate with rapid diagnostics, and assess impacts on vaccine effectiveness studies and resource allocation.