mRNA Seasonal Influenza Vaccine Shows Superiority in Adults

Key Takeaways

• Investigators observed a relative vaccine efficacy of 26.6% with mRNA-1010, and the authors concluded superiority versus standard-dose licensed vaccines for the prespecified endpoint.
• Cases of RT-PCR–confirmed, protocol-defined influenza-like illness caused by influenza A or B were observed less often with mRNA-1010 from at least 14 days after vaccination through season end.
• Solicited reactions were more frequent with mRNA-1010, most were mild to moderate and transient, and serious adverse event rates were low in both groups.

In adults 50 years or older, trivalent mRNA-1010 outperformed a standard-dose comparator over one influenza season, with relative vaccine efficacy of 26.6% and a 95% confidence interval of 16.7 to 35.4. In a phase 3 trial of seasonal influenza prevention in an older adult population, participants were assessed against a licensed vaccine rather than placebo during the reported season.

The trial used a randomized, double-blind, active-controlled design and enrolled adults 50 years of age or older. Among 40,703 participants who received study vaccination, 20,350 received trivalent mRNA-1010 at 37.5 μg total and 20,353 received the licensed standard-dose comparator. The primary efficacy endpoint was relative vaccine efficacy against RT-PCR–confirmed, protocol-defined influenza-like illness caused by influenza A or B. Assessment began at least 14 days after vaccination and continued through the end of the influenza season. Median follow-up was 181 days, with a range of 1 to 227 days, and the hierarchy prespecified noninferiority, superiority, and higher-level superiority thresholds.

The primary endpoint occurred in 411 of 20,179 mRNA-1010 recipients, or 2.0%, and in 557 of 20,124 comparator recipients, or 2.8%. For RT-PCR–confirmed influenza-like illness, that separation corresponded to a relative vaccine efficacy of 26.6%, with a 95% confidence interval of 16.7 to 35.4. These events met the protocol definition for influenza-like illness caused by influenza A or B during the prespecified assessment period. The primary analysis satisfied each step of the planned testing sequence. The authors concluded that mRNA-1010 was superior to standard-dose licensed vaccines for prevention of this endpoint in adults 50 years or older.

Solicited adverse reactions were more frequent with mRNA-1010 than with the comparator, although most were mild to moderate and transient. Injection-site pain was reported in 65.8% versus 29.8%, fatigue in 45.1% versus 20.3%, headache in 37.8% versus 18.0%, and myalgia in 35.4% versus 11.6%. Serious adverse events occurred in 2.2% of mRNA-1010 recipients and 1.9% of comparator recipients. Three serious adverse events in the mRNA-1010 group and two in the comparator group were considered vaccine-related.