Background

Existing influenza vaccines are largely produced using traditional egg-based cultivation techniques. Typically, it takes more than six months to supply actual vaccines based on the influenza virus information predicted by the World Health Organization (WHO). During this lengthy vaccine production period, the virus often mutates, leading to a persistent problem where the vaccine does not match the circulating strain. Furthermore, the virus undergoes genetic adaptation while growing inside eggs, further reducing the actual preventive efficacy. As a result, the scientific community has focused on messenger RNA (mRNA) platforms, which can rapidly initiate production lines if only the virus's gene sequence information is available. By eliminating the egg-based cultivation step and using chemical synthesis, the manufacturing time can be reduced to just a few weeks. Finally, the first influenza vaccine based on this mRNA platform has passed the first regulatory hurdle and is entering the commercialization phase.

Key Findings

The U.S. Food and Drug Administration (FDA) has approved mFLUSIVA (development code: mRNA-1010), the first mRNA-based influenza vaccine developed by Moderna. This approval is for individuals aged 50 years and older, and the approval form varies depending on the age group. For adults aged 50 to 64, formal approval was granted based on the results of a Phase 3 clinical trial (NCT06602024) involving approximately 40,000 participants. In this trial, the group that received mFLUSIVA demonstrated a relative vaccine efficacy (RVE) approximately 26.6% higher compared to the group that received the existing standard-dose influenza vaccine, proving its superiority. For individuals aged 65 years and older, rapid approval was granted based on immunogenicity data, and a confirmatory clinical trial to demonstrate actual preventive efficacy will be required in the future. The vaccine is a quadrivalent formulation targeting influenza A (H1N1, H3N2) and B (Yamagata, Victoria) viruses. As a technology that can rapidly replace the changing virus strains each year, this platform can complete design changes within a few weeks after securing the gene sequence, compared to the several months required for the existing egg-based vaccine cultivation process. This demonstrates the ability to deliver a vaccine that matches the circulating strain to patients in a timely manner. In addition, mRNA vaccines have the advantage of not only activating the body's immune system to induce neutralizing antibodies but also broadly stimulating T-cell immune responses. A study conducted in June showed that the duration of the antibody response was even longer compared to existing influenza vaccines, indicating improved efficacy.

Significance and Prospects

The approval of this mRNA influenza vaccine is interpreted as a turning point in the influenza vaccine manufacturing process, which has continued for decades. It shows that the vaccine market, which has been constantly reacting to influenza virus mutations each year, now has a production structure that can outpace the speed of virus outbreaks. The scientific community expects that the vaccine's actual preventive efficacy will be significantly improved because it does not involve the virus adaptation that occurs during egg-based cultivation. However, there are still challenges to be solved before widespread distribution and market adoption. In the clinical trials, the incidence of temporary adverse reactions such as local pain, fatigue, and headache at the injection site was relatively more frequent compared to existing vaccines. In order to increase the acceptance of the influenza vaccine, which needs to be administered annually, technical improvements are needed to improve the safety-related adverse reaction indicators. The logistics cost of controlling the ultra-low temperature distribution network, which requires temperatures of -70°C, is also a factor that will negatively affect the competition with conventional influenza vaccines, which are mainly distributed at room temperature. As a way to overcome this distribution convenience limitation, research is underway to improve the formulation to reduce the storage temperature. In the future, how Moderna and other developers will address the improvement of distribution conditions and the reduction of adverse reactions will be the key to determining the landscape of large-scale influenza vaccination.