Daily Respiratory Research Analysis
Maternal RSVpreF vaccination in a large phase 3 RCT showed robust protection against severe infant RSV lower respiratory tract illness through 6 months and strong maternal–neonatal antibody transfer. Nasal epithelial transcriptomics across diverse youth cohorts identified T2-high, T17-high, and dual-low asthma endotypes with distinct pathways. A drug-based, no-wash phenotypic imaging probe accurately identified EGFR-activating mutations in lung cancer tissues, potentially accelerating treatment
Summary
Maternal RSVpreF vaccination in a large phase 3 RCT showed robust protection against severe infant RSV lower respiratory tract illness through 6 months and strong maternal–neonatal antibody transfer. Nasal epithelial transcriptomics across diverse youth cohorts identified T2-high, T17-high, and dual-low asthma endotypes with distinct pathways. A drug-based, no-wash phenotypic imaging probe accurately identified EGFR-activating mutations in lung cancer tissues, potentially accelerating treatment decisions beyond DNA sequencing.
Research Themes
- RSV prevention via maternal immunization
- Asthma endotyping using nasal epithelial transcriptomics
- Phenotypic diagnostics for EGFR mutations in lung cancer
Selected Articles
1. Image-Based Phenotypic Profiling Enables Rapid and Accurate Assessment of EGFR-Activating Mutations in Tissues from Lung Cancer Patients.
A covalent, quenched TKI-derived probe enables no-wash, real-time imaging of mutant EGFR, distinguishing mutant from wild-type tumors in vivo and predicting EGFR mutations in patient tissues with 94% accuracy (98% with IHC). This phenotypic imaging approach complements or accelerates DNA-based testing and may streamline EGFR-TKI decision-making.
Impact: Introduces a practical, high-accuracy phenotypic diagnostic that could shorten turnaround time and integrate functional protein-level readouts into lung cancer care.
Clinical Implications: If validated prospectively, this probe could complement or, in some settings, precede sequencing to rapidly stratify patients for EGFR-TKI therapy from biopsy material, especially when tissue is limited or turnaround time is critical.
Key Findings
- Designed a covalent, quenched EGFR-TKI probe enabling no-wash real-time imaging of EGFR in living cells.
- Distinguished EGFR-mutant from wild-type tumors in mice via fluorescence intensity with high contrast.
- Predicted EGFR mutations in patient tumor tissues with 94% accuracy; 98% when integrated with IHC.
Methodological Strengths
- Rational probe design enabling covalent, specific engagement of EGFR kinase with no-wash imaging.
- Validation across systems: living cells, murine models, and human tumor biopsies with quantitative accuracy.
Limitations
- Clinical validation sample size not specified and likely limited; prospective, multicenter studies are needed.
- May not capture rare/complex EGFR alterations or co-mutations; requires viable tissue and imaging infrastructure.
Future Directions: Prospective head-to-head comparisons with NGS in diverse cohorts; expansion to resistance mutations and other oncogenic kinases; workflow integration for real-world turnaround and cost-effectiveness.
2. Efficacy, Safety, and Immunogenicity of the MATISSE (Maternal Immunization Study for Safety and Efficacy) Maternal Respiratory Syncytial Virus Prefusion F Protein Vaccine Trial.
In this global phase 3 RCT of 7,420 pregnant participants, maternal RSVpreF vaccination reduced severe, medically attended infant RSV lower respiratory tract illness by 82.4% at 90 days and 70.0% at 180 days post birth. The vaccine elicited robust maternal responses and efficient antibody transfer to newborns with no new safety signals.
Impact: Provides definitive, large-scale randomized evidence supporting maternal RSV immunization to protect infants through 6 months, addressing a major global respiratory burden.
Clinical Implications: Supports widespread implementation of maternal RSVpreF vaccination to prevent severe infant RSV illness up to 6 months, with strong maternal–neonatal immunogenicity and reassuring safety.
Key Findings
- Vaccine efficacy against severe, medically attended infant RSV LRTI was 82.4% (90 days) and 70.0% (180 days).
- Robust maternal immune responses with highly efficient transplacental transfer across multiple subgroups.
- Final safety profile remained consistent with primary analysis with no new safety concerns.
Methodological Strengths
- Phase 3 randomized, double-blind, placebo-controlled, multinational design with large sample size.
- Prespecified clinical endpoints and registered protocol; included immunogenicity subset for mechanistic insight.
Limitations
- Efficacy reported through 180 days; longer-term infant outcomes were not assessed.
- Immunogenicity assessed in a subset; regional heterogeneity in outcomes requires continued monitoring (addressed in companion analyses).
Future Directions: Assess durability beyond 6 months, co-administration strategies, real-world effectiveness across regions, and integration with infant monoclonal prevention programs.
3. Transcriptomic Profiles in Nasal Epithelium and Asthma Endotypes in Youth.
Across three youth asthma cohorts (total N≈459), nasal epithelial transcriptomics reproducibly identified T2-high, T17-high, and T2low/T17low endotypes. T2-high showed higher IgE/eosinophils and IL-13 pathway enrichment, while T17-high showed IL-17/neutrophil signaling—implicating non–T2 pathways in a large fraction of youth asthma.
Impact: Provides a scalable, minimally invasive molecular stratification for youth asthma and highlights T17-driven biology that may inform targeted therapies beyond type 2 inflammation.
Clinical Implications: Nasal transcriptomic profiling could guide endotype-based therapy selection in youth, including consideration of non–type 2 targets (e.g., IL-17/neutrophil pathways) where T2 biomarkers are low.
Key Findings
- Identified three reproducible nasal transcriptomic endotypes: T2HIGH, T17HIGH, and T2LOW/T17LOW across three cohorts.
- T2HIGH showed higher total IgE (≈584–869 IU/mL) and eosinophils (≈343–560 cells/mL) vs T2-low profiles.
- Differential expression meta-analysis: 3516 DEGs (T2HIGH) linked to IL-13 signaling; 2494 DEGs (T17HIGH) linked to IL-17/neutrophil pathways.
Methodological Strengths
- Multi-cohort analysis with consistent profiling methods and cross-cohort replication.
- Integrated clinical and immunologic correlates (IgE, eosinophils, lung function) with pathway analyses.
Limitations
- Cross-sectional design limits causal inference and prediction of treatment response.
- Cohorts enriched for Puerto Rican and Black/African American youths may require validation in broader populations.
Future Directions: Prospective studies linking nasal endotypes to biologic response, exacerbation risk, and longitudinal stability; development of clinical assays for scalable implementation.