Does Annual Flu Vaccination Blunt the Next Shot? A Korean Trial Is Testing It

Many older adults get a flu shot every fall, often for years. A nagging question is whether repeated doses make each new one work a little less well. A trial registered in Korea is designed to measure exactly that.

The trial is registered as NCT07838298, sponsored by Korea University Guro Hospital, with the National Research Foundation of Korea as collaborator and a site in Seoul. It plans to enroll 180 participants, including older adults (65+) and a younger adult reference group aged 19 to 49 who receive standard dose.

It has four arms: three older-adult arms (standard-dose as the active comparator, MF59-adjuvanted, which adds an immune booster, and high-dose) plus the younger standard-dose reference arm. Its questions are whether the vaccines produce different immune responses, how immune aging shapes them, and whether responses change with repeated annual vaccination. Primary outcomes are antibody measures and fold-rise at one month, yearly for up to three years. Secondary outcomes include B and T cells, nasal IgA and molecular profiling. Primary completion is estimated for December 2028.

One point is easy to misread. The registry sets no requirement for prior flu vaccination history; it excludes only vaccines given in the four weeks before enrollment. Here, 'repeated vaccination' means the annual doses given during the study, not years of shots beforehand.

The scientific question is well founded. The landmark comparison came in 2014, when a randomized trial of nearly 32,000 adults 65 and older, published in the New England Journal of Medicine, found that a high-dose vaccine produced higher antibody levels and about 24 percent fewer laboratory-confirmed flu cases than standard dose (1.4 versus 1.9 percent of participants).

The repeat-vaccination concern is real but unsettled. A 2026 observational study of older adults in China found that people vaccinated in consecutive seasons started with higher antibody levels but had smaller fold-rises after the new shot. Antibody levels did not differ between groups at 30, 90 or 180 days, and the authors concluded protection was comparable. Earlier Hong Kong studies of adults 75 and older also found lower fold-rises with repeat vaccination but similar seroprotection, so the Chinese cohort is not the only evidence.

A 2026 review in Frontiers in Immunology argues that serial vaccination may activate regulatory T cells that reduce antibody titers, and that aging memory T cells may worsen this. That is a hypothesis-building review, not settled evidence.

Flu remains a major cause of hospitalization and functional decline in older adults, and a serious illness can permanently set back strength and independence. If repeated vaccination does blunt response, stronger formulations might seem to matter more for long-time vaccinees. If it does not, the reassuring message is to keep vaccinating every year.

The 'stronger formulations' idea is the weakest part of this argument. A 2025 analysis of the PIVOT trial found that effects of prior vaccination persisted even with enhanced (adjuvanted or recombinant) vaccines in older adults. A better vaccine may therefore not erase the repeat-vaccination effect.

This is also an immune-response trial. Antibody levels are a stand-in for protection, not the same thing. All registered outcomes are immunologic; none covers infections, hospitalizations or survival. A difference between vaccine types would not, by itself, explain the role of repeated vaccination. Those are separate questions.

With 180 participants split across four groups, three of them older adults, each olderadult arm will have fewer than 60 people, so the trial can detect only fairly large differences. Results are years away.

• If you are 65 or older, keep getting an annual flu vaccine; nothing here suggests skipping it. • Ask your doctor or pharmacist whether a high-dose or adjuvanted vaccine is right for you; these are designed for older adults. • If you have a weakened immune system or a history of vaccine reactions, review your options with your doctor.

• Recruitment progress and any changes to the registry record. • Results, estimated for after December 2028, ideally broken down by year of vaccination. • Larger studies that link repeated vaccination to infections and hospitalizations, not just antibody levels.

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