Respiratory Syncytial Virus Vaccination in Solid Organ Transplant Recipients: Interim Findings From a Phase 3 Trial of mRNA-1345

BACKGROUND: Solid organ transplant (SOT) recipients are at increased risk for severe respiratory syncytial virus (RSV) disease due to chronic immunosuppression. METHODS: In this ongoing, open-label, phase 3 trial, adults ≥18 years with a history of liver, kidney, or lung transplant received 2 doses of mRNA-1345 RSV vaccine (50 µg) 56 days apart. Primary endpoints were tolerability, safety, and RSV-A/RSV-B neutralizing antibody (nAb) responses on Day 85; secondary endpoints included immunogenicity on Days 29 and 181. Cell-mediated immunity was an exploratory endpoint assessed in a subset of participants. RESULTS: 146/150 participants (median: age, 57 years; time since transplant, 4.7 years) received both doses. Reactogenicity was mild to moderate and transient. No vaccine-related discontinuations, deaths, adverse events of special interest (AESIs), or events of transplant rejection were reported within 28 days after any dose. One dose was immunogenic across all SOT types, with 4.9- and 3.4-fold increases in RSV-A/RSV-B nAb GMTs by Day 29, respectively. A second dose resulted in modest additional increases over baseline (RSV-A, 7.1-fold; RSV-B, 5.2-fold). Added benefit of the second dose was more apparent in participants with kidney and lung transplant,