Immune correlates analysis of mRNA-1345 RSV vaccine efficacy clinical trial.
Summary
In a correlates analysis of the pivotal mRNA-1345 trial in older adults, day-29 RSV-A/B neutralizing titers and prefusion F IgG inversely correlated with RSV-LRTD and ARD. A 10-fold increase in RSV-A nAb reduced event hazards by ~55–60%, supporting these markers as correlates of protection.
Key Findings
- Day-29 RSV-A nAb: 10-fold increase associated with HR 0.44 for RSV-LRTD-2+, 0.41 for RSV-LRTD-3+, and 0.45 for RSV-ARD.
- Consistent inverse correlations were observed for RSV-B nAb and prefusion F IgG.
- Findings designate day-29 nAb and preF IgG as correlates of risk and protection for clinically relevant RSV endpoints.
Clinical Implications
Day-29 nAb and preF IgG can inform booster timing, immunobridging for new populations or formulations, and may guide regulatory acceptance of surrogate endpoints in RSV vaccine development.
Why It Matters
Defines robust immune correlates for an RSV vaccine, enabling immunobridging, accelerated decision-making, and potential use of surrogate endpoints.
Limitations
- Correlational nature; thresholds for protection and durability not fully defined
- Generalizability limited to older adults; timing beyond day 29 not assessed in this analysis
Future Directions
Define protective thresholds and durability, validate correlates across age groups and vaccine platforms, and assess utility for regulatory immunobridging.
Study Information
- Study Type
- RCT
- Research Domain
- Prevention
- Evidence Level
- II - Secondary analysis of a pivotal randomized controlled vaccine efficacy trial
- Study Design
- OTHER