#19,339
Hopefully the daunting title of today's paper won't deter both of my readers, because the preprint in question is well worth reading given what we are already seeing with the approach of the Northern Hemisphere's flu season:
Due to the time it takes to manufacture and deploy hundreds of millions of doses, recommendations on the composition of the northern hemisphere’s vaccine must be made in February of each year, while recommendations on the southern hemisphere’s vaccine are made in late September.South Korean CDC Issues Early Seasonal Flu Epidemic Advisory
Japan MHLW Reports Unusually Early Start to the Fall Flu Season
Flu viruses, however, don't stop evolving. Last year, we famously saw the late emergence of a `drifted' H3N2 subclade K virus (see Increasing Concerns Over A `Drifted' H3N2 Virus This Flu Season), which was less than an ideal match to the vaccine.
Last February, following observed antigenic changes in all three circulating strains (H1N1, H3N2, Influenza B), the WHO recommended changes to all 3 components of the fall vaccine, which is being delivered now. Later this month, they will meet to discuss next year's Southern Hemisphere flu vaccine.
None of this suggests we face an imminent `vaccine failure'. Despite last year's mismatch with H3N2 Subclade K, the flu vaccine still produced a beneficial VE (Vaccine Effectiveness) according to the MMWR.
Interim 2025–26 seasonal influenza VE estimates were derived from three U.S. VE networks. Among children and adolescents, VE was 38%–41% against influenza-associated outpatient visits and 41% against influenza-associated hospitalization. Among adults aged ≥18 years, VE was 22%–34% against influenza-associated outpatient visits and 30% against influenza-associated hospitalization.
Among their findings, the authors identified 72 serum samples in which an H1N1 D.3.1.1 virus carrying G155E was more than twofold less effectively neutralized than a comparable virus without that mutation. Those samples tended to come from teenagers and young adults (roughly 15–25 years old).
It is well recognized that one's first flu exposure makes a significant, and lasting, impression on the immune system (see Nature: Declan Butler On How Your First Bout Of Flu Leaves A Lasting Impression). People in this age cohort were first exposed to H1N1 either during or after the 2009 pandemic, whereas older adults were likely first exposed to the previous H1N1 virus.
There is a lot here to unpack, and there are still a lot of questions of how these emerging variants will impact this year's flu season (or beyond).
Those wishing a deeper dive will want to follow the link to read the full 18-page preprint, but fair warning, much of it is highly technical. I'll have a bit more after the break.
Near real-time data on the human neutralizing antibody landscape to influenza virus in summer of 2026 shows antigenic advance of H3N2 subclade K region D mutants and H1N1 D.3.1.1 Sa mutants
Caroline Kikawa, Andrew Butler, John Huddleston, Sam A Turner, Heidi Peck, Janet A Englund, Kirsten Lacombe Michael Busch, Marion C Lanteri, Mars Stone, Bryan Spencer, Alexander L Greninger, Derek J Smith, Stephanie Wallace, Helen S Marshall, Shidan Tosif, Scott E Hensley, Ian G Barr, Jesse D Bloom
doi: https://doi.org/10.64898/2026.09.15.751855
This article is a preprint and has not been certified by peer review [what does this mean?].
Preview PDF
Abstract
Human seasonal influenza evolves rapidly, necessitating twice yearly decisions about whether to update the strains in the vaccine. To help inform this decision, we have been using high-throughput sequencing-based neutralization assays to make twice yearly measurements of how recent human sera neutralize current human H3N2 and H1N1 strains.
Here we provide the third installment in this series of measurements by reporting 47,851 titers representing neutralization of 148 viral strains by 325 human sera collected between April and August of 2026.Our measurements show that new H3N2 subclade K strains with mutations in antigenic region D and new H1N1 subclade D.3.1.1 strains with mutations in antigenic region Sa (such as G155E) have reduced neutralization by human sera, with notable heterogeneity in the impact of some of these mutations across sera from different individuals. This paper is accompanied by an interactive summary (https://jbloomlab.github.io/flu-seqneut-2026/summary.html) that enables detailed exploration of the results, and all titer data are publicly available for further analysis to aid vaccine antigen selection and studies of viral evolution.
(SNIP)
Discussion
We have measured how a large set of human sera neutralize current human H3N2 and H1N1 influenza strains. Our results show that the two subclades that spread widely over the last year (subclade K for H3N2 and D.3.1.1 for H1N1) are now spawning descendants with reduced neutralization by human sera.
These descendant strains have HA mutations that are associated with decreased neutralization, some of which have arisen independently in different combinations.
- For H3N2, mutations at sites in antigenic region D (e.g., 223 and 222) have arisen recurrently and reduce neutralization; mutations at sites in antigenic regions A and B are also present in strains with reduced neutralization (e.g., 145, 156, 157).
- For H1N1, strains with mutations at sites in antigenic region Sa (e.g., 155 and 157) have arisen recurrently and reduce neutralization; mutations at sites in antigenic regions Sb and Ca1 (e.g., 190 and 205) are also present in strains with reduced neutralization.
However, the diversity of new antigenic variant strains makes it challenging to use our data alone to determine which strains will dominate a year from now. For H1N1, our data show that D.3.1.1 is antigenically advanced over D.3.1, and virtually all human H1N1 influenza observed over the last few months is D.3.1.1 or a descendant strain.
However, it is uncertain which more antigenically advanced variant of H1N1 will spread over the next year— G155E reduces neutralization of all H1N1 strains and has recently arisen recurrently, but it occurs in multiple genetic backgrounds and there are also other antigenic mutations that could outcompete it. Similarly, although our data identify multiple new antigenic variant strains of subclade K, it remains unclear which of these new variants will dominate over the next year.
In addition to these antigenic changes, we are also following concurrent reports of creeping antiviral resistance in H1N1 (see Eurosurveillance: Emergence and spread of NA-I223V and NA-S247N double-mutant A(H1N1)pdm09 influenza viruses with reduced oseltamivir susceptibility in the Netherlands and beyond, 2023 to 2026).
While neither of these trends are anywhere near a crisis point, they are reminders that the global `fluscape' is constantly changing, and that every flu season remains highly unpredictable.
Reduced VE or not, this year's vaccine is still expected to provide modest - perhaps even substantial - benefit. So I'll still gladly roll up my sleeve this fall, albeit with slightly tempered expectations.
I'll avail myself of antivirals if I am infected. But I'll also be wearing a facemask in crowded indoor venues, using copious amounts of hand sanitizer, and avoiding crowds whenever possible.
Because prevention is always preferable to a treatment.
