Weekly Respiratory Research Analysis
This week was dominated by actionable RSV research and advances in mucosal vaccination: a phase 3 correlates analysis identified Day-29 neutralizing antibodies and prefusion F IgG as robust correlates of protection for an mRNA RSV vaccine, enabling immunobridging. A phase 1 inhaled adenoviral COVID-19 vaccine study established a lung-directed mucosal platform and highlighted minimal baseline lung mucosal immunity after IM mRNA priming. A global Bayesian synthesis mapped infant RSV hospitalizatio
Summary
This week was dominated by actionable RSV research and advances in mucosal vaccination: a phase 3 correlates analysis identified Day-29 neutralizing antibodies and prefusion F IgG as robust correlates of protection for an mRNA RSV vaccine, enabling immunobridging. A phase 1 inhaled adenoviral COVID-19 vaccine study established a lung-directed mucosal platform and highlighted minimal baseline lung mucosal immunity after IM mRNA priming. A global Bayesian synthesis mapped infant RSV hospitalization risk by month-of-age and birth month, producing a validated web tool to optimize timing of passive immunization.
Selected Articles
1. Immune correlates analysis of mRNA-1345 RSV vaccine efficacy clinical trial.
Secondary correlates analysis of the pivotal phase 3 mRNA-1345 trial in older adults showed that Day-29 RSV-A/B neutralizing antibody titers and prefusion F (preF) IgG inversely correlated with RSV lower respiratory tract disease and acute respiratory disease endpoints. A 10-fold increase in RSV-A nAb was associated with ~55–60% reduction in hazard for key clinical endpoints, supporting these markers as correlates of protection and potential surrogate endpoints for immunobridging.
Impact: Defines robust, trial-anchored immune correlates for an RSV vaccine—critical for immunobridging, accelerated approvals, and rational booster development across populations and platforms.
Clinical Implications: Day-29 neutralizing titers and preF IgG can guide booster timing, immunobridging for new age groups/formulations, and may be accepted as surrogate endpoints pending regulatory validation—potentially speeding vaccine rollout and tailored strategies for high-risk groups.
Key Findings
- Day-29 RSV-A neutralizing antibody: 10-fold increase associated with HR ≈0.41–0.45 across RSV-LRTD and RSV-ARD endpoints.
- Consistent inverse correlations observed for RSV-B nAb and prefusion F IgG across multiple clinical endpoints.
- Designates Day-29 nAb and preF IgG as correlates of risk and protection, supporting surrogate use for immunobridging.
2. Induction of lung mucosal immunity by a next-generation inhaled aerosol COVID-19 vaccine: an open-label, multi-arm phase 1 clinical trial.
An open-label, multi-arm phase 1 study tested single-dose inhaled adenoviral (HuAd/ChAd) COVID-19 vaccines in adults previously primed with mRNA. The trial established a lung-targeted dose-escalation platform with bronchoscopy-enabled mucosal and blood immune profiling. Notably, baseline lung mucosal immunity was minimally detectable despite prior intramuscular mRNA vaccination, supporting the rationale for mucosal boosting.
Impact: Pioneers a clinically deployable inhaled mucosal vaccine platform with compartmental immune sampling—directly relevant to preventing respiratory infection at the portal of entry and to future variant-adapted booster strategies.
Clinical Implications: If subsequent trials show safety and mucosal immunogenicity, inhaled boosters could complement IM regimens by inducing airway-local immunity—potentially reducing infection, transmission, and severe disease in high-risk populations.
Key Findings
- Implemented a bronchoscopic, dose-escalation phase 1 trial of inhaled HuAd/ChAd vaccines in mRNA-primed adults.
- Baseline lung mucosal immunity was minimal in both previously infected and uninfected participants.
- Protocol integrates compartmental airway sampling to directly measure mucosal responses post-inhalation.
3. Respiratory syncytial virus hospitalisation by chronological month of age and by birth month in infants.
A Bayesian synthesis of published and collaborator datasets estimated infant RSV hospitalization distribution by month-of-age and birth month and developed a validated web tool that projects hospitalization risk by birth month given local seasonality. Globally, hospitalization risk peaks at month 2 and concentrates under 6 months, but the age-distribution varies substantially by birth month—supporting birth-month–tailored passive immunization strategies.
Impact: Delivers actionable, granular estimates and a deployable decision tool to optimize timing of maternal vaccination or monoclonal antibody administration to cover the highest-risk infant window.
Clinical Implications: Programs can align nirsevimab administration or maternal vaccination campaigns with local RSV seasonality and infant birth month to maximize protection during the highest-risk window (around 2 months of age).
Key Findings
- Global hospitalization burden generally peaks at month 2 and concentrates under 6 months of age.
- Significant variation exists in age-distribution of RSV hospitalizations by infant birth month due to local seasonality.
- A validated web-based tool projects hospitalization distribution by birth month to guide immunization timing.