mRNA Influenza Vaccine Shows Improved Protection During the 2024-2025 Flu Season
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Reviewed & Translated by Dat Tien Nguyen, B.A, ScM.
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Posted on May 27th, 2026
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The influenza virus can rapidly mutate due to its genetic variability, allowing it to evade immune recognition and reducing vaccine effectiveness from season to season. In addition, the conventional egg-based vaccine production process can introduce adaptive mutations that alter viral antigens and potentially reduce immune protection. Following the success of mRNA technology during the COVID-19 pandemic, a recent study published in the New England Journal of Medicine evaluated the effectiveness of an mRNA-based vaccine for seasonal influenza.
Funding Source(s): Blackstone Life Sciences and Moderna
The phase 3 clinical trial was conducted during the 2024–2025 influenza season and enrolled approximately 40,000 participants with an average age of 64 years. Around 70% of the participants were from North America, and nearly half had received influenza vaccination during the previous season. Participants were randomly assigned to receive an intramuscular injection of either the standard inactivated influenza vaccine or the investigational mRNA influenza vaccine.
The researchers found that the mRNA influenza vaccine demonstrated a 26.6% greater efficacy in preventing RT-PCR–confirmed influenza infection compared with the conventional inactivated vaccine. The improved protection was most notable against Influenza A/H1N1 and A/H3N2 strains. In contrast, the difference in effectiveness against Influenza B was not statistically significant, likely because fewer Influenza B infections occurred during the study period. Despite the improved protection, the mRNA vaccine was associated with a higher frequency of adverse events. Injection-site pain, fatigue, headache, and myalgia were reported more commonly among participants who received the mRNA vaccine. However, these side effects were generally mild to moderate in severity and resolved within a short period of time.
Funding Source(s): Blackstone Life Sciences and Moderna
The phase 3 clinical trial was conducted during the 2024–2025 influenza season and enrolled approximately 40,000 participants with an average age of 64 years. Around 70% of the participants were from North America, and nearly half had received influenza vaccination during the previous season. Participants were randomly assigned to receive an intramuscular injection of either the standard inactivated influenza vaccine or the investigational mRNA influenza vaccine.
The researchers found that the mRNA influenza vaccine demonstrated a 26.6% greater efficacy in preventing RT-PCR–confirmed influenza infection compared with the conventional inactivated vaccine. The improved protection was most notable against Influenza A/H1N1 and A/H3N2 strains. In contrast, the difference in effectiveness against Influenza B was not statistically significant, likely because fewer Influenza B infections occurred during the study period. Despite the improved protection, the mRNA vaccine was associated with a higher frequency of adverse events. Injection-site pain, fatigue, headache, and myalgia were reported more commonly among participants who received the mRNA vaccine. However, these side effects were generally mild to moderate in severity and resolved within a short period of time.