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

Clinical Snapshot

Key Findings

• P Value: Not reported in abstract

• Effect Size: Single dose: 4.9-fold (RSV-A) and 3.4-fold (RSV-B) increase in neutralizing antibody GMTs by Day 29

• Primary Outcome: RSV-A/RSV-B neutralizing antibody responses at Day 85 with 7.1-fold and 5.2-fold increases respectively after two doses

• Nnt Or Sensitivity: Additional benefit of second dose more apparent in kidney/lung transplant recipients, <2 years post-transplant, and those on mycophenolate

• Confidence Interval: Not reported in abstract

Clinical Application

Two-dose regimen 56 days apart is feasible in transplant clinic settings; mild-moderate reactogenicity profile supports clinical implementation Relevant for Australian transplant centres; would require TGA approval and potential PBS listing for immunocompromised populations. Aligns with NHMRC immunisation guidelines for high-risk groups Adult solid organ transplant recipients, particularly those with kidney or lung transplants, within 2 years of transplantation, or receiving mycophenolate immunosuppression

Abstract

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, <2 years post-transplant, and on mycophenolate. Responses remained above baseline through Day 181. Polyfunctional CD4⁺ T-cell responses were robust and sustained; CD8⁺ responses were also observed. CONCLUSIONS: mRNA-1345 was well tolerated and immunogenic in SOT recipients. A single dose induced nAb responses across subgroups, with potential additional benefit from a second dose in specific groups. Durable antibody and cellular responses support mRNA-1345 as a preventive strategy for RSV in this vulnerable population. CLINICAL TRIALS REGISTRATION: NCT06067230.

References

1. 1.Mayer, E. F., Falsey, A. R., Wolfe, C. R., Herc, E., Burns, F., Kabbani, D., Kumar, D., Mannan, A., She, F., Lan, L., McGrath, S., Kapoor, A., & Priddy, F. (2026). Respiratory Syncytial Virus Vaccination in Solid Organ Transplant Recipients: Interim Findings From a Phase 3 Trial of mRNA-1345. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciag108