How can the immunogenicity and effectiveness of flu vaccines be improved in older adults? Several strategies are available, one being the addition of an adjuvant. For example, the MF59-adjuvanted vaccine has shown superior immunogenicity. However, “we do not have data from controlled and randomized clinical trials showing superior clinical effectiveness versus the standard dose,” Professor Odile Launay, an infectious disease specialist at Cochin Hospital in Paris, France, noted during a press conference. Another option is to increase the antigen dose in the vaccine, creating a high-dose (HD) flu vaccine.
Why is there a need for an HD vaccine? “The elderly population bears the greatest burden from the flu,” explained Launay. “This is due to three factors: An aging immune system, a higher number of comorbidities, and increased frailty.” Standard-dose flu vaccines are seen as offering suboptimal protection for those older than 65 years, which led to the development of a quadrivalent vaccine with four times the antigen dose of standard flu vaccines. This HD vaccine was introduced in France during the 2021/2022 flu season. A real-world cohort study has since been conducted to evaluate its effectiveness in the target population — those aged 65 years or older. The results were recently published in Clinical Microbiology and Infection.
Cohort Study
The study included 405,385 noninstitutionalized people aged 65 years or older matched with 1,621,540 individuals in a 1:4 ratio. The first group received the HD vaccine, while the second group received the standard-dose vaccine. Both the groups had an average age of 77 years, with 56% women, and 51% vaccinated in pharmacies. The majority had been previously vaccinated against flu (91%), and 97% had completed a full COVID-19 vaccination schedule. More than half had at least one chronic illness.
Hospitalization rates for flu — the study’s primary outcome — were 69.5 vs 90.5 per 100,000 person-years in the HD vs standard-dose group. This represented a 23.3% reduction (95% CI, 8.4-35.8; P = .003).
Strengths and Limitations
Among the strengths of the study, Launay highlighted the large number of vaccinated participants older than 65 years — more than 7 million — and the widespread use of polymerase chain reaction flu tests in cases of hospitalization for respiratory infections, which improved flu coding in the database used. Additionally, the results were consistent with those of previous studies.
However, limitations included the retrospective design, which did not randomize participants and introduced potential bias. For example, the HD vaccine may have been prioritized for the oldest people or those with multiple comorbidities. Additionally, the 2021/2022 flu season was atypical, with the simultaneous circulation of the flu virus and SARS-CoV-2, as noted by Launay.
Conclusion
In conclusion, this first evaluation of the HD flu vaccine’s effectiveness in France showed a 25% reduction in hospitalizations, consistent with existing data covering 12 flu seasons. The vaccine has been available for a longer period in the United States and Northern Europe.
“The latest unpublished data from the 2022/23 season show a 27% reduction in hospitalizations with the HD vaccine in people over 65,” added Launay.
Note: Due to a pricing disagreement with the French government, Sanofi’s HD flu vaccine Efluelda, intended for people older than 65 years, will not be available this year. (See: Withdrawal of the Efluelda Influenza Vaccine: The Academy of Medicine Reacts). However, the company has submitted a dossier for a trivalent form for a return in the 2025/2026 season and is working on developing mRNA vaccines. Additionally, a combined flu/COVID-19 vaccine is currently in development.
The study was funded by Sanofi. Several authors are Sanofi employees. Odile Launay reported conflicts of interest with Sanofi, MSD, Pfizer, GSK, and Moderna.
This story was translated from Medscape’s French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.