Seasonal influenza remains one of the most persistent and costly infectious diseases in the United States (US). Each year, millions of Americans become ill, leading to hundreds of thousands of hospitalizations and tens of thousands of deaths. Vaccination remains the best defense, but the protection offered by conventional flu shots changes from year to year, depending on how well the vaccine matches circulating strains.
Recent advances in mRNA vaccine technology, proven during the COVID-19 pandemic, offer the potential for substantial public health gains if applied to influenza. By design, mRNA vaccines are faster to update, more adaptable, and highly scalable. A Phase III clinical trial demonstrated that mRNA influenza vaccines achieve a 26.6% improvement in effectiveness compared with conventional formulations, suggesting the possibility of meaningfully reducing the annual burden of influenza. In this article, we explore how much of the 2024–25 flu burden could have been prevented if mRNA vaccines had been in use.
Methodological Framework
We denote the total population as \(N\), the attack rate as \(A\), the vaccine coverage rate as \(v\), and the efficacy of traditional vaccines as \(\eta_0\), then the influenza burden for the 2024–25 season can be expressed as: $$B_0=AN[(1-\eta_0)v + (1-v)]=AN(1-\eta_0v).$$
Incorporating mRNA Vaccine Effectiveness
Phase III trial evidence suggests that mRNA influenza vaccines are 26.6% more effective than current seasonal vaccines. If such vaccines were deployed, the expected disease burden would instead be: $$B_1=AN(1-\eta_1v),$$ where the efficacy of mRNA vaccines is given by: $$\eta_1=1 – (1-\eta_0) * (1-0.266).$$ This formulation increases the baseline efficacy \(\eta_0\) by adjusting for the relative performance improvement. The relationship between the two burdens can then be expressed as: $$B_1=\frac{1-\eta_1v}{1-\eta_0v}B_0.$$
Parameter Values
Based on the US Centers for Disease Control and Prevention data for the 2024–25 season and a published cost analysis study:
- Traditional influenza vaccine effectiveness was \(\eta_0=0.56\).
- Coverage among the US population (2023–24 season) was \(v=0.472\).
- The observed burden of influenza was:
- 47–82 million illnesses
- 21–37 million medical visits
- 610,000–1.3 million hospitalizations
- 27,000–130,000 deaths
- Average cost per influenza hospitalization (2022–23 season): $11,384–12,896
Estimated Impact of mRNA Vaccines
Applying these parameters, the introduction of mRNA influenza vaccines could have prevented, in the 2024–25 season alone:
- 3.5–6.2 million illnesses
- 1.6–2.8 million medical visits
- 46,000–98,000 hospitalizations
- 2,000–10,000 deaths
- Up to $1.3 billion in hospitalization costs.
Moreover, when accounting for indirect protection through reduced transmission, as many as 36 million additional influenza cases could potentially be averted.
Takeaway
Even in a single season, mRNA vaccines would have a substantial impact on population health and healthcare costs. The one-year financial savings that mRNA can provide by preventing influenza hospitalizations would pay for the cancelled BARDA research budget. These results highlight the value of continued investment in advanced vaccine platforms, not only for pandemic preparedness but also for reducing the recurring annual burden of influenza.