What data sources does the CDC use to estimate 2025-2026 flu vaccine effectiveness against H3N2?
Executive summary
The CDC draws on laboratory surveillance (viral sequencing and antigenic characterization), multiple vaccine effectiveness (VE) networks using a test-negative design, hospitalization surveillance, and international VE studies to estimate 2025–26 influenza vaccine effectiveness against A(H3N2) — notably CDC reports reference FluView virologic data and genetic/antigenic analyses and use four domestic VE networks plus international MMWR evaluations from Southern Hemisphere countries to triangulate VE [1] [2] [3]. Available reports also note limitations: antigenic drift in some H3N2 viruses and early signals of subclade mismatch that reduce confidence in VE estimates [1] [4].
1. What CDC measures of circulating viruses feed VE estimates
CDC’s virologic surveillance underpins VE assessment by sequencing and antigenic testing of viruses reported through FluView and partner labs; those data identify dominant subtypes, clades and drifted hemagglutinin (HA) substitutions that can reduce vaccine match — the agency explicitly reported A(H3N2) HA substitutions and antigenic drift as potential contributors to lower VE in its 2024–25 assessment and in composition notes for the 2025–26 vaccine [1].
2. The domestic VE “networks” and test‑negative studies CDC uses
CDC publishes VE results derived from multiple U.S. vaccine effectiveness networks that apply a test‑negative design comparing vaccinated versus unvaccinated patients with acute respiratory illness who test positive or negative for influenza; CDC’s Flu Vaccines Work pages and the MMWR describe four VE networks (e.g., IVY, US Flu VE, VISION, NVSN) used to estimate subtype‑specific VE including for A(H3N2) [2] [5].
3. Hospitalization and severe‑disease surveillance streams
CDC integrates hospitalization surveillance such as FluSurv‑NET and severe acute respiratory infection (SARI) surveillance into VE and burden estimates; MMWR Southern Hemisphere reports cite SARI and ILI (influenza‑like illness) case‑patient data and adjusted VE estimates against hospitalization that inform expectations for the Northern Hemisphere [3] [6].
4. International and Southern Hemisphere studies that inform early 2025–26 VE expectations
CDC and U.S. analysts use Southern Hemisphere interim VE studies (published in MMWR) as early signals of vaccine performance; the MMWR reported pooled VE from eight Southern Hemisphere countries estimating ~37% VE against A(H3N2) hospitalization in 2025 and about half effectiveness overall against outpatient visits and hospitalizations, providing comparative data used by CDC and WHO in interpretation [3] [6].
5. Genetic and antigenic characterization from WHO and partner labs
WHO vaccine composition meetings, human serology panels and ferret antisera assays produce antigenic data CDC cites when assessing match. WHO and CDC materials document serology and hemagglutination or neutralization assay results against vaccine reference viruses and circulating subclades — these lab data are essential inputs to VE interpretation because they reveal whether vaccine‑induced antibodies neutralize circulating H3N2 variants [7] [1].
6. Real‑time wastewater and sequencing signals used as situational awareness (limited VE role)
Reporting notes that CDC and other groups are monitoring wastewater for influenza A as a rising activity signal; such tools inform timing and spread but do not by themselves produce VE estimates. News accounts reference CDC wastewater surveillance and municipal WastewaterSCAN data as early activity indicators [8].
7. What the data say specifically about H3N2 and uncertainty in VE
CDC’s summary of 2024–25 and early 2025 surveillance states some A(H3N2) viruses showed HA substitutions and antigenic drift, which likely contributed to lower VE against H3N2; public reports and European technical notes flag emergence of a divergent H3N2 subclade K with multiple HA substitutions and limited real‑world VE data, underscoring uncertainty about vaccine match and effectiveness for 2025–26 [1] [4].
8. Strengths, limitations and how CDC hedges its conclusions
Strengths: CDC triangulates laboratory antigenic/genetic data, multiple VE networks, hospitalization surveillance, and international VE reports to build VE estimates [2] [3] [1]. Limitations: antigenic drift and novel subclades (e.g., K) can emerge after vaccine strain selection, creating potential mismatch; CDC and European authorities explicitly state real‑world VE data for 2025–26 remain limited and early estimates may change as more data accumulate [1] [4].
9. Practical takeaway for clinicians and public health planners
CDC continues to recommend vaccination while acknowledging reduced match risks; early surveillance and Southern Hemisphere VE suggest modest to moderate protection overall but lower VE against some H3N2 viruses, so planners should combine vaccination campaigns with preparedness for increased hospitalizations and antiviral use where indicated [3] [1] [9].
Limitations: available sources do not mention the full internal CDC modeling algorithms or exact weightings applied across data streams when producing a single VE estimate; those procedural details are not described in the provided documents (not found in current reporting).