6 notes on G155E, the mutation fueling an earlier flu season

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A single mutation in the H1N1 influenza virus — G155E — is emerging as the defining feature of a flu season that has arrived months ahead of schedule and may slip past some people’s immunity, researchers told Nature, CNN and Today. 

Becker’s reported Oct. 5 that H1N1 had overtaken H3N2 in early West Coast surveillance. The mutation now drawing scrutiny helps explain why.

Six notes:

1. The season started early and in an unusual place. Flu activity began climbing in late August and has risen steadily since, an unusually early start that hit Pacific states first rather than the South, where U.S. seasons typically begin. Alex Greninger, MD, PhD, told CNN the season arrived about 2.5 months ahead of a typical year. Dr. Greninger is head of the division of infectious disease diagnostics at the University of Washington’s department of laboratory medicine in Seattle. Nationally, Walgreens data show the season tracking about four weeks ahead of recent years.

2. The early numbers are running well above last year’s. Flu test positivity hit 5.7% during the week ending Oct. 17, up from less than 1% the same week a year earlier, according to CDC data. Outpatient visits for flu-like illness reached 2.2%, higher than the prior two seasons. As of Oct. 21, the CDC estimated flu infections were growing or likely growing in 44 states, with Louisiana and Hawaii already at moderate levels. In the region spanning Arizona, California, Hawaii and Nevada, at least 10% of flu tests came back positive.

3. H1N1 has displaced last year’s “superflu.” Influenza A H1N1 is driving the vast majority of U.S. cases — 96% of subtyped positives during the week ending Sept. 26, per CDC data, and about 98% of samples in Dr. Greninger’s lab. That is a flip from last winter, when the highly mutated H3N2 subclade K dominated. H1N1 is the same lineage behind the 2009 “swine flu” pandemic.

4. What makes G155E concerning. The circulating virus — H1N1 (pdm09), subclade D.3.1.1 — has picked up a single new mutation, G155E, at a site important for generating protective antibodies, according to Andrew Pekosz, PhD, a virologist at Johns Hopkins Bloomberg School of Public Health in Baltimore, who spoke to Today. 

The mutation was first flagged in September in Seattle in a bioRxiv preprint led by Jesse Bloom, PhD, a virologist at Fred Hutchinson Cancer Center in Seattle. Dr. Greninger’s lab detected G155E in 13 of 17 H1N1 samples complete enough to sequence.

5. It may evade some pre-existing immunity — especially in the young. Dr. Bloom’s team tested blood from 260 people in Australia and the U.S. against 148 influenza A viruses circulating by mid-2026 and found that strains carrying G155E were, in some cases, less well recognized by existing antibodies. Antibodies from teenagers and young adults were especially poor at recognizing the variant, likely because they have had less exposure to similar H1N1 viruses. H1N1 has historically hit young people hardest. In Japan, surges among children forced school and day care closures and prompted officials to move up vaccination clinics.

6. The vaccine is a partial match — and the advice is to get it now. Because this year’s shots were formulated in the spring, before G155E spread, the H1N1 component may not be well-matched if the mutation dominates, Dr. Bloom told Nature, though he cautioned it is too early to know. 

Scott Hensley, PhD, a virologist at the University of Pennsylvania in Philadelphia told Nature the H3N2 and influenza B components appear well-matched. Experts stressed that a mismatch means reduced protection, not none. 

“This is one of those seasons where the key message is to go get vaccinated now,” Dr. Greninger told CNN. He added that a second, more conventional wave could follow once H1N1 peaks.

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