How should clinical guidance change if 2025-2026 H3N2 vaccine effectiveness is low?
Executive summary
Early surveillance shows a drifted H3N2 “subclade K” that laboratory data say is antigenically different from the 2025–26 vaccine strain, but real-world early estimates from England still show substantial protection in children (72–75% vs ED/hospital) and modest protection in adults (32–39%) [1] [2]. Public-health authorities therefore must balance a likely partial vaccine mismatch with clear evidence that vaccination and antivirals still reduce severe outcomes [1] [3].
1. What the data actually show: mismatch in the lab, partial protection in the clinic
Genetic and antigenic analyses document that subclade K (J.2.4.1) is divergent from the northern-hemisphere 2025–26 H3N2 vaccine virus and ferret antisera show reduced reactivity to K viruses, indicating potential immune escape [1] [4]. Despite that drift, early test-negative VE studies from England report VE of about 72–75% against emergency-department attendances and admissions in children and 32–39% in adults — evidence that real-world protection can remain clinically meaningful even with antigenic drift [1] [2] [3].
2. Practical clinical implications if VE is low: pivot to diagnostics and antivirals
If later surveillance confirms substantially lower vaccine effectiveness, clinical guidance should emphasize prompt testing to guide treatment for patients at risk of progression, and lower thresholds to prescribe antivirals for high-risk outpatients and inpatients — testing and antiviral treatment “guide clinical management” regardless of vaccination status, per CDC briefings for the 2025–26 season [5]. Several sources stress that antiviral susceptibility has remained favourable in recent seasons, supporting antiviral-first strategies when vaccine protection weakens [6].
3. Prioritize high-risk groups and enhanced vaccine messaging
When VE falls, public-health guidance historically focuses on protecting those with the highest risk of severe outcomes. Early analyses and national guidance documents continue to recommend vaccination for high-risk and immunocompromised patients — professional societies (IDSA) advise strong vaccination for immunocompromised people because vaccines still reduce hospitalizations even when VE is imperfect [7]. Messaging must be explicit: even partial VE reduces severe disease while also reminding clinicians that vaccination coverage among hospitalized patients was low in prior seasons, indicating an opportunity to reduce burden through targeted uptake [6].
4. Surveillance and real‑time VE: the deciding evidence
Policy changes should follow robust, real‑time VE and sequence surveillance. European and UK reports underline the need for “robust real‑world vaccine effectiveness studies as the season progresses” to determine the clinical impact of subclade K and to guide any mid-season clinical or policy shifts [8] [1]. Available reporting warns that laboratory antigenic data alone cannot fully predict clinical VE; the early UK VE estimates illustrate this disconnect and argue for caution before wholesale guideline changes [1] [9].
5. Alternative and complementary measures clinicians must use
If vaccine performance is low, clinicians must rely more on non‑vaccine levers: earlier testing, use of antivirals for eligible patients, stricter infection control in congregate settings, and prioritizing prophylactic or therapeutic measures for long‑term care populations. CDC guidance for the 2025–26 season explicitly states testing can guide antiviral use for people at higher risk regardless of vaccination [5]. Public-health advisories from the UK similarly highlight vaccination plus respiratory hygiene as combined layers of protection even amid drift [10].
6. Tradeoffs, hidden agendas and uncertainties to watch
Some sources emphasize the political and procedural disruptions to immunization advice this season (e.g., changes to advisory processes), which could influence how rapidly authorities adjust recommendations or how clinicians interpret “shared clinical decision-making” versus firm guidance [11] [12]. Also, early-season VE estimates come from one country and time window; available sources note real‑world VE data remain limited and geographically variable, so global extrapolation is not warranted yet [8] [1].
7. Bottom line for clinicians: vaccinate, test, treat — but watch the data
Current evidence supports continuing vaccination because it reduces severe outcomes in children and likely in adults even if partial mismatch exists [1] [3]. Simultaneously, clinicians should lower thresholds for diagnostic testing and antiviral treatment for high‑risk patients, follow real‑time VE reports to adjust practice, and advocate for high vaccination coverage in at‑risk groups given prior seasons’ low uptake among hospitalized patients [6] [5] [7].
Limitations: available sources do not provide long‑term, season‑wide VE estimates or direct randomized comparisons of antiviral strategies under a confirmed low‑VE scenario; policy choices should follow ongoing surveillance and formal public‑health updates [8] [1].