Modified mRNA Flu Vaccine Shows Superior Protection in Major Global Trial
USA: A major phase 3 clinical trial has provided promising evidence that a modified mRNA (modRNA) influenza vaccine may offer stronger protection against flu than current licensed vaccines.
The study, published in The New England Journal of Medicine and led by David Fitz-Patrick from the East-West Medical Research Institute in Honolulu, evaluated the vaccine’s performance across multiple countries during the 2022–2023 flu season.
Traditional flu vaccines, many of which rely on egg-based production techniques developed in the 1940s, have long struggled to keep pace with the rapid evolution of influenza viruses. These vaccines require several months to manufacture, forcing researchers to select strains far in advance—often before the season’s dominant variants are known. As a result, yearly vaccine effectiveness has fluctuated widely, ranging from 19% to 60% over the past 15 years.
To address this problem, researchers have increasingly turned to newer technologies. The FDA has previously approved cell-based and recombinant influenza vaccines, which offer faster production and improved accuracy over egg-derived platforms. Building on this progress, scientists are now exploring mRNA vaccines—the same technology that enabled rapid global deployment of COVID-19 vaccines during the pandemic.
In the latest trial, 18,476 healthy adults aged 18 to 64 were randomly assigned to receive either the experimental quadrivalent modRNA vaccine or a standard inactivated quadrivalent vaccine. Participants were enrolled in the United States, South Africa, and the Philippines. The primary goal was to compare vaccine efficacy against laboratory-confirmed influenza associated with influenza-like illness, beginning 14 days after vaccination.
The study led to the following findings:
- The modRNA influenza vaccine showed 34.5% higher efficacy than the licensed comparator, fulfilling both noninferiority and superiority criteria.
- Almost all influenza-like illness cases were attributed to circulating A/H3N2 and A/H1N1 strains, with minimal influenza B activity during the study period.
- Immunogenicity results indicated that the modRNA vaccine produced antibody responses comparable to the standard vaccine for influenza A strains, but it did not meet noninferiority criteria for influenza B strains.
- Short-term side effects were more common with the modRNA vaccine: local reactions occurred in 70.1% of recipients compared with 43.1% in the control group.
- Systemic symptoms such as fever, headache, and fatigue were reported in 65.8% of the modRNA group versus 48.7% of the comparator group.
- Fever was noted in 5.6% of modRNA recipients, compared with 1.7% in those receiving the conventional vaccine.
- Despite the higher reactogenicity, both vaccines demonstrated a similar overall safety profile, with only a small number of serious adverse events reported.
Experts, including editorial authors Hana M. El Sahly and Robert L. Atmar, note that further data are needed for groups at highest risk from influenza, particularly adults over 65, people with chronic conditions, and children. Pfizer, the study’s sponsor, is now developing an updated version of the mRNA flu vaccine that will be tested in older adults.
"The results mark another step toward modernizing flu vaccination and potentially improving annual protection as influenza viruses continue to evolve unpredictably," the study authors concluded.
Reference: https://www.nejm.org/doi/full/10.1056/NEJMoa2416779
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