Moderna’s mRNA-based RSV vaccines clinical trial halted.
SciFocus/Dec 18, 2024 — The development of vaccines against Respiratory Syncytial Virus (RSV) for infants has hit a critical juncture following concerning safety signals observed in clinical trials of Moderna’s mRNA-based RSV vaccines. While adult vaccines have shown success, pediatric versions may not only fail to protect but could also potentially exacerbate severe respiratory illnesses. This revelation raises urgent questions about vaccine safety and efficacy for the youngest, most vulnerable populations.
“We need to remain humble about what we actually know. My main concern is that we invest in basic research to find a solution for children between 6 months and 5 years of age.” – Barney Graham, Virologist and Immunologist
Key Highlights:
- Clinical Trial Safety Signals:
- Moderna’s mRNA vaccines, mRNA-1345 and mRNA-1365, showed higher rates of severe/very severe lower respiratory tract infections (LRTIs) in vaccinated infants aged 5-7 months compared to the placebo group.
- Trials in Panama revealed 5 severe RSV cases in 40 vaccinated children vs. 1 in the placebo group.
- Potential Vaccine-Associated Enhanced Respiratory Disease (VAERD):
- Observed responses raise concerns about immune priming leading to inappropriate immune responses, similar to historical RSV vaccine challenges from the 1960s.
- VAERD may involve ineffective antibodies and blunted T-cell responses.
- Immune Response Analysis:
- Preliminary results indicated elevated neutralizing antibody (nAb) responses but limited data on cell-mediated immunity in younger participants.
- Trends suggest differences in cytokine responses (e.g., increased IL-5 in RSV-naïve participants).
- FDA Actions:
- The FDA has suspended enrollment in 11 RSV vaccine trials targeting RSV proteins but allowed continuation of live, attenuated vaccine trials.
- Maternal antibody vaccines and monoclonal antibody therapies are still available, but these only offer temporary protection.
- Broader Implications:
- The Moderna trials underscore gaps in understanding how vaccines interact with the developing immune system of infants.
- Enhanced scrutiny of mRNA vaccine platforms in pediatric settings is critical to advancing safe and effective RSV immunization strategies.
Looking Ahead:
While the development of RSV vaccines for infants faces hurdles, the scientific community is committed to advancing research. Live attenuated vaccines, which mimic natural infections, offer a promising path forward. Continued investment in immunological studies and cautious trial designs will be crucial in overcoming these setbacks and addressing the global need for a pediatric RSV vaccine.
References:
- Cohen, J. (2024, December 13). Science.
- FDA Advisory Panel Meeting Notes.
- National Institute of Allergy and Infectious Diseases (NIAID).
