Dr. Eric Mayer from Moderna presented Phase III trial data at IDWeek 2025 demonstrating that the company's mRNA-1345 respiratory syncytial virus (RSV) vaccine is safe and effective in solid organ transplant recipients aged 18 years and older. The findings address a critical need for RSV vaccination data in immunocompromised populations, who face significantly increased risk of RSV infection and mortality.
Trial Design and Patient Population
The open-label study (NCT06067230) enrolled 150 solid organ transplant recipients, including 48 kidney recipients, 46 lung recipients, 48 liver recipients, and eight multi-organ recipients. All participants received their transplant at least 180 days prior to trial enrollment and were administered a two-dose regimen of 50 micrograms mRNA-1345 approximately 60 days apart.
The primary objective focused on safety assessment through adverse event monitoring, while immunogenicity was evaluated by measuring RSV-A and RSV-B neutralizing antibodies geometric mean titers after the two-dose regimen administered two months apart.
Safety Profile Consistent with Known Data
Trial results showed that mRNA-1345 maintained a safety profile similar to its established profile in the general population. Solicited adverse reactions were predominantly grade 1-2, occurring within 1-2 days of injection and resolving within 2-3 days. Injection site pain emerged as the most frequent local reaction, while fatigue, headache, and myalgia represented the primary systemic reactions.
Only one grade 4 adverse event was reported as treatment-related, though this was confounded by the administration of rabbit anti-thrombocyte globulin 14 days prior to the event. Notably, no adverse events led to vaccine discontinuation or deaths within 28 days of any dose.
Immunogenicity Across Transplant Types
The vaccine demonstrated immunogenicity across all solid organ transplant types, with measurable increases in RSV-A and RSV-B neutralizing antibody geometric mean titers observed by day 29 following a single dose. These immune responses proved durable through day 181, with geometric mean fold rises remaining above baseline for both RSV-A and RSV-B consistently across all transplant types.
Participants within two years of transplant showed enhanced neutralizing antibody responses after the second dose, with the effect most notable in kidney and lung recipients. Additionally, those receiving the immunosuppressant mycophenolate mofetil demonstrated increased antibody responses following the second dose, suggesting that recent transplant recipients and those on certain immunosuppressive agents may derive particular benefit from a two-dose regimen.
Clinical Context and Market Position
RSV represents a common respiratory pathogen causing significant global disease burden, with immunocompromised status significantly associated with increased infection risk and mortality. Key opinion leaders have previously noted the need for additional data on RSV vaccines in immunocompromised populations.
mRESVIA, Moderna's commercial name for mRNA-1345, has received approval in major markets including the United States, European Union, Japan, and Australia for preventing RSV lower respiratory-tract disease in adults over 60 years and in adults aged 18-59 years at increased risk. The vaccine became the third RSV prophylactic to enter the global market following its initial U.S. approval in May 2024, after GSK's Arexvy and Pfizer's Abrysvo, both first approved in the U.S. in May 2023.
The study findings provide clinicians with crucial data for understanding mRNA-1345's response in immunocompromised patients, particularly relevant given that guidelines in major markets recommend RSV vaccination in solid organ transplant recipients.
