Newly approved mRNA flu vaccine provides a more effective flu shot for older adults
In the pivotal phase 3 trial, the mRNA vaccine was as effective in participants 65 years or older as it was in trial participants overall, although whether its clinical efficacy is superior to that of the high-dose or other enhanced flu vaccines remains to be seen.
With a median follow-up of 181 days, the phase 3 trial found that the mRNA vaccine across all ages was approximately 27% more effective in preventing polymerase chain reaction–confirmed illness caused by any influenza A or B strain than the standard dose comparator vaccine, researchers reported in May. About 2% of participants who received the mRNA vaccine were diagnosed with the flu, compared with 2.8% who received a comparator vaccine.
Among the more than 19 000 trial participants who were at least 65 years of age, the mRNA vaccine’s relative efficacy was the same as that for all ages, which suggests benefits similar to those of high-dose and other enhanced influenza vaccines in the oldest adults, according to the authors. (Previous research has shown that the relative efficacy of high-dose flu vaccines vs standard-dose shots is about the same as that of the mRNA flu vaccine vs standard-dose shots, Goodman explained.)
Overall, those who received the mRNA vaccine were more likely to report experiencing the adverse events researchers asked about, including injection site pain, fatigue, headache, and muscle aches, which have also been seen after immunization with mRNA COVID-19 vaccines. Most adverse events were mild to moderate and transient, the scientists noted.
In another Moderna-sponsored phase 3 trial, researchers studied the immunogenicity of mRNA-1010 compared with a standard-dose comparator vaccine in adults ages 18 through 64 years or the high-dose flu vaccine in about 3000 people 65 years or older. The mRNA vaccine demonstrated an immune response superior to both the comparator vaccines, the scientists reported in February 2025.
“Based on immunogenicity data, this vaccine will perform in a superior manner” to the high-dose vaccine, Osterholm said. “Obviously, they’re going to be doing postmarketing evaluation.”
Accelerated approval is based on surrogate end points, in this case the immunogenicity data for people 65 years or older. Higher immunogenicity, such as increased neutralizing antibody titers, often correlates with better protection, but Moderna must confirm its vaccine’s clinical benefit in a postmarketing trial involving individuals who are at least 65 years old.
According to the FDA briefing document for the June VRBPAC meeting, the postmarket, or phase 4, confirmatory study will enroll approximately 400 000 adults 65 years or older in each of 2 flu seasons. Vaccine clinics that administer the shots will alternate weekly between mRNA-1010 and an agreed upon CDC-recommended vaccine throughout the flu seasons.
https://jamanetwork.com/journals/jama/fullarticle/2853094