mRNA Flu Vaccine Outperforms Standard Shot by 34.5%
- Nov 20
- 2 min read
Pfizer’s new mRNA-based flu vaccine has demonstrated statistically superior efficacy compared to conventional flu shots in a large, global Phase 3 clinical trial, marking a significant advance in influenza prevention. The study, published in the New England Journal of Medicine, involved over 18,000 participants aged 18 to 64.
The results indicate that the mRNA vaccine was 34.5% more effective than the standard conventional vaccine (Fluzone) at preventing laboratory-confirmed influenza-like illnesses. This relative efficacy translates to 30 fewer cases in the mRNA group. The improved protection was driven almost entirely by strong results against Influenza A strains (H3N2 and H1N1). The impact of influenza remains significant, with over 440,000 laboratory-confirmed notifications and approximately 1,000 deaths recorded in Australia in one recent year.
Experts suggest applying the mRNA platform—the same technology popularized during the COVID-19 pandemic—to influenza is a logical progression with many potential benefits. One key advantage is that manufacturing mRNA vaccines is quicker and easier, potentially allowing scientists to match circulating strains closer to the actual flu season.
While more effective, the mRNA vaccine was associated with higher reactogenicity. Recipients of the mRNA shot reported more frequent local and systemic side effects, such as fatigue, headache, muscle pain, and fever. For instance, 5.6% of those receiving the mRNA vaccine reported fevers, compared to 1.7% in the traditional flu shot group. These reactions were mostly mild to moderate and typically short-lived (lasting 1–2 days).
The higher frequency of side effects is considered plausible given that the mRNA vaccine generated a stronger immune response, including robust neutralizing antibodies and T-cell responses. Importantly, the rates of severe and life-threatening side effects were low and similar across both trial groups. There were also no reported cases of myocarditis or pericarditis.
Despite the promising findings, the study revealed limitations. The vaccine induced a weaker antibody response against influenza B strains, and there were too few circulating cases during the trial to draw meaningful conclusions on its effectiveness against Influenza B. Furthermore, the trial was limited to adults 18–64; an unpublished component of the trial involving subjects 65 years and over failed to show enhanced protection, indicating that existing high-dose vaccines remain the best option for the elderly for now.
The superior efficacy demonstrated in this large Phase 3 trial is an important step toward adding mRNA vaccines to the tools available to combat influenza. However, the issue of higher mild side effects may make the vaccine less attractive to some patients, potentially making it harder to gain acceptance in a climate of high vaccine suspicion. Pfizer is currently in discussions with health authorities regarding the path to licensure.
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Keywords: mRNA Flu Vaccine
mRNA Flu Vaccine
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