#18,891
I'll be rolling up my sleeve for my 20th consecutive seasonal flu shot next week, but I am keenly aware that there are some studies suggesting that with repeated flu vaccinations, comes the risk of mounting a diminished immune response.
This idea made headlines a decade ago (see Helen Branswell's report Getting a flu shot every year? More may not be better), following a preliminary report from Wisconsin’s Marshfield Clinic Research Foundation on the effectiveness of repeated flu vaccination in kids.A similar report appeared earlier in the CMAJ (see Repeated flu shots may blunt effectiveness). However, these assumptions were based on limited data, during a time when the H3N2 subtype was undergoing rapid changes (see (CDC HAN Advisory On `Drifted’ H3N2 Seasonal Flu Virus).
Three years later (2018), the Marshfield Clinic released a follow-up report (below) which supported the receipt of the flu vaccine every year.
Friday, October 26, 2018
Also that year, in CMAJ Research: Repeated Flu Vaccinations Reduce Severity of Illness In Elderly, we looked at a study that found that repeated vaccinations over two or more years cut the rate of severe influenza illness in half.A Marshfield Clinic Research Institute study recently found that getting a flu vaccination one year did not reduce vaccine effectiveness the next year in children, findings that support current recommendations for children to be vaccinated annually against influenza.
The study was conducted by Huong McLean, Ph.D., and Edward Belongia, M.D., of the Center for Clinical Epidemiology and Population Health at Marshfield Clinic Research Institute, and was published in JAMA Network Open.
(Continue . . . )
In 2019, a systematic review of the literature (The impact of repeated vaccination on influenza vaccine effectiveness: a systematic review and meta-analysis) lent additional support to the idea of getting the flu vaccine every year, despite some decline in VE among people receiving back-to-back yearly flu vaccinations.Reassuringly, 2022's ISIRV: Immune Response From Repeated Seasonal Flu Vaccinations concluded: `Repeated vaccination provides similar or enhanced protection as compared with single vaccination in first-time vaccinees.'
Today we have yet another study, which looked at 250 healthcare workers (median age ~38 &~78% female) from Norway over 4 consecutive (2010/11–2013/14) influenza seasons, who were divided into 4 cohorts based on vaccine receipt:
- Current & Previous Vaccinated in the current season and previous season
- Current Only Vaccinated in the current season but not the previous season
- Previous Only Vaccinated in the previous season but skipped vaccination in the current
- Unvaccinated Received no vaccine in either current or prior season
Key findings included:
- Unvaccinated healthcare workers showed high influenza infection rates—up to 72% infected over just four seasons.
- Vaccination significantly boosted protective antibody levels across all subtypes.
- A/H1N1 immunity grew stronger with repeated vaccination; antibody durability improves after 3+ doses.
- A/H3N2 immunity grew weaker with repeated vaccinations - with natural infection or hybrid immunity producing stronger protection.
- While repeated A/H3N2 vaccination instilled some degree of seroprotective immunity (1) Antibody levels were significantly lower compared to H1N1, and (2) Protection waned more quickly compared to H1N1
This is a lengthy, detailed, and at time technical report, so I've only reproduced the abstract and some excerpts from the conclusion below. Follow the link for a deeper dive.
I'll have a postscript after you return.
Published: 29 September 2025
Effects of repeated influenza vaccination and infection on durable seroprotection in healthcare workersMai-Chi Trieu, Amit Bansal, Marianne Sævik, Sonja Ljostveit, Åsne Jul-Larsen & Rebecca Jane Cox
npj Vaccines volume 10, Article number: 213 (2025) Cite this article
Abstract
Rapid evolution of seasonal influenza viruses necessitates annual vaccine reformulation to match circulating strains. Healthcare workers (HCWs) and high-risk groups are prioritised for annual influenza vaccination. However, repeated annual vaccination may affect immune protection. This study investigated the hemaglutination-inhibition (HI) antibody responses following influenza infection or repeated seasonal vaccination over four seasons in 250 HCWs with well-defined vaccination histories.
Unvaccinated HCWs had high infection rates, with pre-existing antibodies providing protection. Infection or hybrid immunity generated higher antibody responses to A/H3N2 viruses than vaccination alone, whereas vaccination induced more durable A/H1N1 and B virus-specific antibodies. Vaccination boosted seroprotective antibodies, irrespective of previous vaccination histories. Moreover, repeated vaccination with the same virus for more than three consecutive seasons blunted antibody responses, while updating vaccine strains improved immunity.
Annual influenza vaccination of HCWs should be strengthened to increase uptake, but next-generation influenza vaccines must improve vaccine immunogenicity, particularly against A/H3N2 viruses.
(SNIP)
In conclusion, seasonal influenza vaccination was effective in preventing influenza infection and boosting antibodies to above seroprotective levels in HCWs.Repeated annual vaccination increased antibody persistence, which correlated with lower antibody responses to subsequent vaccinations. Repeated vaccinations with the same viruses more than thrice blunted antibody responses to vaccines, whereas updating the vaccine viruses likely improved antibody responses to vaccinesOur findings highlight the need to improve vaccine immunogenicity, particularly against A/H3N2 viruses, and demonstrate that repeated annual vaccination may have complex effects on antibody responses. More research is required to conclusively determine whether repeated annual vaccination has any negative effect on protection and the mechanism behind.We support continuing the current recommendation of annual influenza vaccination in HCWs. However, more refined vaccine strategies are essential to mitigate any potential negative effects of repeated vaccination while maintaining the benefits of seasonal vaccines.
While this is a single study, and it deals with a panoply of influenza viruses from nearly 15 years ago, it provides additional reassurance on the practice of getting an annual flu vaccine.
It also reminds us that while `good', today's flu vaccines are not great.
They don't protect as well, or as broadly, as we'd like. They are most useful in blunting the effects of infection, rather than preventing it (see CDC Hopes to `Reset' Flu Vaccine Expectations With New Campaign).
The human immune system is stunningly complex, and only partially understood. Individual responses to vaccination can vary depending upon age, health, and past (and first) influenza exposures (see Nature: Declan Butler On How Your First Bout Of Flu Leaves A Lasting Impression).Add in rapidly evolving Influenza A viruses, with H3N2 being particularly labile (see The Enigmatic, Problematic H3N2 Influenza Virus), it is little wonder that decades of promises that a `universal flu vaccine' was close, have fallen short.
But just as seatbelts don't guarantee you'll walk away unscathed from a collision, current seasonal flu vaccine can markedly reduce your chances of a severe infection.
So, while we wait for a `better' vaccine solution - for me, at least - some protection is better than none.
