Background

Influenza, a seasonal illness that claims hundreds of thousands of lives worldwide each year, is prevented through widespread influenza vaccination. Traditional influenza vaccines are primarily manufactured by growing viruses in embryonated eggs or cell cultures, followed by inactivation. This conventional manufacturing process can lead to antigenic drift as the vaccine virus adapts to the embryonated eggs, resulting in a mismatch between the vaccine and circulating strains. Furthermore, the production of vaccines takes several months, making it difficult to respond quickly to rapidly emerging variants.

The rapid and flexible capabilities demonstrated by the messenger RNA (mRNA) platform during the Coronavirus Disease 2019 (COVID-19) pandemic have emerged as a new alternative in the field of influenza vaccine development. mRNA vaccines can be produced within weeks once the viral genetic information is available, allowing for agile responses to annual changes in circulating influenza strains. Recently, Moderna's mRNA-based seasonal influenza vaccine, mRNA-1010, announced the results of a large-scale Phase 3 trial and received recommendations from the advisory committee of the U.S. Food and Drug Administration (FDA), bringing the commercialization of the next-generation influenza vaccine closer to reality.

However, the medical community questions whether the mRNA vaccine can replace existing high-dose vaccines or vaccines containing adjuvants, which are widely used in the elderly. Demonstrating superiority to standard-dose vaccines in clinical trials alone may not be sufficient to guarantee competitiveness in real-world clinical settings.

Key Findings

The Phase 3 Fluent trial, led by Professor Leroux-Roels of Ghent University in Belgium, evaluated the safety and efficacy of mRNA-1010 in 40,703 adults aged 50 years and older. In this randomized, double-blind trial, the mRNA-1010 group showed better preventive efficacy compared to the control group, which received a standard-dose vaccine.

The researchers used a method to confirm the incidence of influenza-like illness using real-time polymerase chain reaction (RT-PCR). The analysis showed that the proportion of participants in the mRNA-1010 group who experienced influenza-like illness was only 2.0%. In contrast, the standard-dose vaccine group had an incidence rate of 2.8%. This means that the relative vaccine efficacy of mRNA-1010 compared to the standard vaccine was 26.6%.

In the safety assessment, the mRNA vaccine's unique ability to induce a high immune response was reflected. Predictable adverse reactions, such as pain at the injection site, fatigue, headache, and muscle pain, were reported more frequently in the mRNA-1010 group than in the standard vaccine group. Specifically, pain at the injection site was 65.8% versus 29.8%, and fatigue was 45.1% versus 20.3%, but most were mild to moderate and transient. The incidence of serious adverse events was 2.2% in the mRNA-1010 group and 1.9% in the standard vaccine group, with no significant difference between the two groups.

Significance and Prospects

This study is significant in that it demonstrates that mRNA technology can provide better protection than standard vaccines in the field of seasonal influenza prevention. The scientific basis has been established for drastically reducing the vaccine production period from several months to a few weeks, minimizing the risk of mismatch.

However, the impact of these clinical results on actual influenza vaccination strategies for the elderly needs to be observed more cautiously. The clinical trial did not use high-dose vaccines or vaccines containing adjuvants, or recombinant vaccines, which are widely used for elderly influenza prevention, as a control group. For example, for individuals aged 65 years and older, the U.S. Advisory Committee on Immunization Practices (ACIP) recommends these enhanced vaccines as a priority. Recombinant vaccines have also been shown to reduce the incidence of influenza by 30% compared to standard vaccines.

To ensure that mRNA-1010 is widely selected in clinical practice, it is necessary to accumulate direct comparative clinical data with existing enhanced vaccines. Research that demonstrates that it has a substantial preventive benefit that outweighs the relatively high incidence of adverse events is a key next step.