Sunday, November 09, 2025

Increasing Concerns Over A `Drifted' H3N2 Virus This Flu Season

Credit NIAID

#18,939

Although hard data is always limited this early in the season, there are increasing concerns that this year's crop of H3N2 seasonal flu viruses may have `drifted' away from the H3N2 components (see below) of the current (fall 2025) influenza vaccine.
    • an A/Croatia/10136RV/2023 (H3N2)-like virus; and
    • an A/District of Columbia/27/2023 (H3N2)-like virus;
This doesn't come as a complete surprise, as 6 weeks ago the WHO announced  strain changes for next year's (2026) Southern Hemisphere flu vaccine (for both H1N1 and H3N2). 

Since decisions must be made more than 6 months in advance on what flu strains to include, there is always the chance of mutations emerging, particularly in the H3N2 subtype - which typically evolves at faster rate than H1N1 (see The Enigmatic, Problematic H3N2 Influenza Virus).
We saw this scenario play out back in 2014 (see CDC HAN Advisory On `Drifted’ H3N2 Seasonal Flu Virus) and again in 2017, when changes in the H3N2 virus resulted in disappointing VE (Vaccine Effectiveness) numbers (see MMWR: Interim Estimates of 2017–18 Seasonal Influenza Vaccine Effectiveness (VE) — US Feb. 2018).

While we've seen media reporting from Japan, China, and more recently the UK indicating an early - and robust - start to the fall flu season, the U.S. government shutdown means we have limited data on what is happening here. 

Overnight, the CBC News (Canada) ran the following report, which quotes Dr. Danuta Skowronski as saying `The difference between the circulating H3N2 virus and what's in the vaccine is quite a bit different . . . '.  


Alarm bells abroad, spread of a new form of H3N2 provide warnings as influenza cases start ticking up

Friday's Canadian respiratory virus surveillance report doesn't elaborate on the exact changes, but notes under Antigenic Characterization that 75% of H3N2 viruses tested this fall show reduced titers against the vaccine strain: 

Influenza A(H3N2)

A/District of Columbia/27/2023 (H3N2)-like virus is the influenza A(H3N2) component of the 2025-2026 Northern Hemisphere influenza vaccine.

  • Six influenza A(H3N2) were antigenically similar to A/District of Columbia/27/2023 (H3N2)-like virus using antisera raised against cell-grown A/District of Columbia/27/2023 (H3N2)-like virus.
  • 18 influenza A(H3N2) viruses showed reduced titer with antisera raised against cell-grown A/District of Columbia/27/2023 (H3N2)-like virus.

While that doesn't negate the value of the flu vaccine, it suggests we may see lower effectiveness against H3N2 infection and/or hospitalization.   

From the UK's most recent  National flu and COVID-19 surveillance report: 30 October 2025 (week 44) (publish Nov 6th), we see a much smaller sampling, but of the two viruses characterised, neither were a close match to the vaccine strain.

The characterisation of circulating H3 viruses show that H3 viruses are diverse (genetically). Most sequenced viruses to date belong to genetic clade J.2.4.1
Antigenic characterisation of currently circulating H3N2 viruses collected via surveillance in England is ongoing and currently only includes two H3N2 viruses. However, observations published from the WHO influenza vaccine composition meeting (VCM) in September 2025 suggest low reactivity of these viruses with post-infection ferret antisera raised against A/District of Columbia/27/2023 (cell) and A/Croatia/10136RV/2023 (egg), the H3N2 components in the NH vaccine.
It is not yet clear how vaccine effectiveness against clinical disease may be affected by these observations. Vaccines typically still provide protection against severe clinical disease when drifted strains are seen with only a modest reduction in effectiveness.
A(H3N2): Two A(H3N2) viruses have been antigenically characterised and none (0%) were similar to reference viruses representative of the A/Croatia/10136RV/2023 (H3N2)‑like Northern Hemisphere 2025/26 (H3N2) vaccine strain.

A finding which has led to similar concerns being expressed overnight by UK influenza researchers (see BBC Experts say this could be the worst flu season for a decade - here's why). 

While we haven't seen many H3 viruses characterized this fall, we do have the following cautionary report by Dr. Skowronski et al. (published Oct 31st) which describes an emerging `Subclade K  H3N2 virus' in the most recent Southern Hemisphere (SH) flu season. 

Emergence of seasonal influenza A(H3N2) variants with immune escape potential warrants enhanced molecular and epidemiological surveillance for the 2025–2026 season
Authors: Suzana Sabaiduc, Samantha E Kaweski, Lea Separovic, Ruimin Gao, Charlene Ranadheera, Nathalie Bastien, and Danuta M Skowronski Danuta.Skowronski@bccdc.ca 
Publication: Journal of the Association of Medical Microbiology and Infectious Disease Canada
Advance Access
https://doi.org/10.3138/jammi-2025-0025

PDF
 

In the paper's `lay summary' the authors warn that this `. . . . vaccine mismatched A(H3N2) variant ' is `. . . projected to predominate during the northern hemisphere’s 2025–2026 influenza season.'
Fortunately, even a poorly matched vaccine is expected to provide some degree of protection - at least against severe infection - and so I'm glad I've already gotten my seasonal flu/COVID shots for this fall. 

But I expect I'll be cinching my face mask just a little bit tighter, and slathering my hands with alcohol sanitizer a little more often, when I'm out and about during the upcoming holiday/flu season.  

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