mRNA-1345 Vaccine: Safe & Effective in Solid Organ Transplant Recipients

For solid organ transplant recipients – a population particularly vulnerable to respiratory syncytial virus (RSV) – a new vaccine shows promising results. Data presented at IDWeek 2025 and published in preliminary form indicate that Moderna’s mRNA-1345 RSV vaccine is both safe and effective in generating an immune response in these patients. This offers a potential new layer of protection against a virus that can cause severe illness in those with weakened immune systems.

RSV and the Immunocompromised: A Heightened Risk

RSV is a common respiratory virus that typically causes mild, cold-like symptoms. However, for individuals with compromised immune systems, such as those who have received solid organ transplants, RSV can lead to serious complications, including pneumonia and even death. Transplant recipients take immunosuppressant medications to prevent organ rejection, which unfortunately also leaves them more susceptible to infections like RSV. Research confirms that this group experiences a significantly increased risk of severe RSV disease.

mRNA-1345: Trial Design and Key Findings

The ongoing Phase 3 trial, identified as NCT06067230, involved 150 adult solid organ transplant recipients – including those who had received a liver, kidney, or lung transplant. Participants received two doses of the mRNA-1345 vaccine, 50 micrograms each, administered 56 days apart. The study focused on assessing the vaccine’s tolerability, safety, and ability to stimulate an immune response.

Researchers found the vaccine to be well-tolerated, with reactogenicity – temporary side effects like pain or swelling at the injection site – described as mild to moderate. Importantly, no participants discontinued the trial due to vaccine-related issues, and there were no reports of death, serious adverse events, or organ rejection within 28 days of vaccination.

The vaccine proved immunogenic, meaning it triggered an immune response. A single dose led to a 4.9-fold and 3.4-fold increase in neutralizing antibodies against RSV-A and RSV-B, respectively, by day 29. A second dose provided a modest additional boost, increasing antibody levels to 7.1-fold and 5.2-fold. The benefit of the second dose appeared more pronounced in kidney and lung transplant recipients, those who had received their transplant within the past two years, and those taking mycophenolate, an immunosuppressant drug.

Beyond antibody responses, the study also observed robust and sustained polyfunctional CD4⁺ T-cell responses, and also CD8⁺ responses, indicating a broader immune activation. These cellular responses are crucial for long-term protection against viral infections.

Understanding Neutralizing Antibodies and Cellular Immunity

Neutralizing antibodies are proteins produced by the immune system that can block a virus from infecting cells. They are a key indicator of protection against viral diseases. Cellular immunity, involving T-cells, provides a different layer of defense. T-cells can directly kill infected cells and help coordinate the immune response. The combination of both antibody and cellular responses suggests a potentially durable and comprehensive immune protection offered by the mRNA-1345 vaccine.

What the Data Doesn’t Notify Us

It’s important to note that this is an ongoing, open-label trial. “Open-label” means both researchers and participants know who is receiving the vaccine, which can introduce a degree of bias. The study primarily assessed immunogenicity – the ability to generate an immune response – and did not directly measure the vaccine’s effectiveness in preventing RSV infection or severe disease. Further research is needed to determine how well the vaccine protects transplant recipients from actually getting sick with RSV.

Existing RSV Vaccines and the Immunocompromised

The development of mRNA-1345 comes after the recent approval of other RSV vaccines, including GSK’s Arexvy and Pfizer’s Abrysvo, both approved in the US in May 2023, and Moderna’s mRESVIA, approved in May 2024. These vaccines were initially authorized for older adults and adults at high risk of severe RSV disease. However, the question of their safety and efficacy in immunocompromised individuals remained. Key opinion leaders have emphasized the need for more data specifically addressing this population, highlighting the gap in knowledge regarding RSV vaccination in those with weakened immune systems.

What Comes Next: Continued Monitoring and Potential Guidance Updates

Researchers will continue to follow participants in the NCT06067230 trial to assess the durability of the immune response and monitor for any long-term safety concerns. The data collected will be crucial in informing potential recommendations for RSV vaccination in solid organ transplant recipients. Public health agencies, such as the Centers for Disease Control and Prevention (CDC), will likely review the findings as they develop into available and update their guidance accordingly. Clinicians caring for transplant patients should stay informed about the latest research and recommendations to provide the best possible care for their patients. The ongoing nature of the trial means that further analysis and reporting are expected, potentially refining our understanding of the vaccine’s benefits and optimal use in this vulnerable population.