For the estimated 500,000+ solid organ transplant recipients living in the United States, respiratory syncytial virus is far more than a seasonal nuisance — it can trigger severe lower respiratory tract disease and graft compromise. Understanding whether mRNA-based RSV vaccines can mount meaningful immune responses in chronically immunosuppressed individuals is therefore a genuinely high-stakes clinical question.
This interim Phase 3 open-label trial enrolled 150 adults (median age 57, median 4.7 years post-transplant) with liver, kidney, or lung transplants who received two 50 µg doses of mRNA-1345 — the same mRNA-stabilized prefusion F-protein vaccine platform approved for older adults — administered 56 days apart. A single dose drove 4.9-fold and 3.4-fold increases in RSV-A and RSV-B neutralizing antibody geometric mean titers by Day 29, respectively. The second dose produced additional but modest gains (7.1-fold and 5.2-fold over baseline), with the incremental benefit most pronounced in kidney and lung transplant recipients, those within two years of transplant, and individuals on mycophenolate — a potent B-cell suppressor. Antibody levels remained above baseline at Day 181. CD4⁺ T-cell polyfunctional responses were robust and durable; CD8⁺ responses were also detected. Critically, no transplant rejection events or vaccine-related discontinuations occurred within 28 days of any dose.
This finding carries important contextual weight. Immunosuppressed cohorts are systematically underrepresented in pivotal vaccine trials, yet they bear disproportionate infectious disease burden. The antibody fold-rises here, while lower than those seen in immunocompetent older adults, are arguably clinically meaningful given the near-zero baseline protection in this population. The mycophenolate subgroup data is particularly instructive: it suggests a mechanistic rationale for the two-dose strategy that mirrors dosing logic in COVID-19 mRNA vaccination of transplant recipients. Key limitations include the open-label design, the absence of an efficacy endpoint against confirmed RSV illness, and the relatively small cohort. Longer follow-up and efficacy data are needed before definitive clinical guidance can be established, making this an important but preliminary signal.