Phase 3 trial finds Moderna mRNA flu vaccine outperforms standard vaccine in older adults

Moderna’s mRNA-based seasonal flu vaccine, mRNA-1010, demonstrated superior protection against influenza in adults aged 50 and older compared to standard-dose flu shots, according to a phase 3 trial published in the *New England Journal of Medicine*. The study, conducted across 301 sites in 11 countries during the 2024-25 Northern Hemisphere flu season, enrolled 40,703 participants. Researchers found that 2.0% of those receiving mRNA-1010 contracted flu, compared to 2.8% in the standard-dose group, resulting in a 26.6% relative vaccine efficacy (rVE). The trial also showed consistent protection across flu strains: 29.6% against A/H1N1, 22.2% against A/H3N2, and 29.1% against B/Victoria. Among participants aged 65 and older, the efficacy remained at 27.4%. Additionally, flu-related healthcare visits were 33.7% lower in the mRNA-1010 group, with 80 cases compared to 120 in the standard-dose group. The study highlights mRNA-1010’s potential advantage over traditional egg-based vaccines, which can introduce mutations and reduce strain matching. Moderna’s technology allows for quicker updates to match circulating flu strains more accurately. Side effects were more common with the mRNA vaccine—65.8% reported injection-site pain versus 29.8% in the standard-dose group—but serious adverse events occurred at similar rates (2.2% vs. 1.9%). The findings follow regulatory uncertainty earlier this year when the FDA initially declined to review Moderna’s application for mRNA-1010, later reversing course amid concerns about shifting standards under Health and Human Services Secretary Robert F. Kennedy Jr. The World Health Organization estimates the flu causes up to 5 million severe illnesses and 650,000 deaths annually, with older adults facing higher risks. Researchers noted that while other enhanced flu vaccines (high-dose, adjuvanted, or recombinant-based) also improve protection in older adults, their effectiveness varies yearly depending on strain matching. The study suggests mRNA-1010 could offer a more reliable alternative due to its adaptability and direct targeting of viral proteins.