Impact and effectiveness of Australia's 2025 hybrid RSV immunisation program: results from the PAEDS-FluCAN Network.

BACKGROUND

Australia introduced a hybrid Respiratory Syncytial Virus (RSV) Maternal and Infant Protection Program (RSV-MIPP) in 2025, using National Immunisation Program-funded RSV vaccine for pregnant people from 28 weeks' gestation and jurisdiction-funded nirsevimab. We estimated real-world effectiveness and assessed the impact of the RSV-MIPP program across a participating surveillance network.

METHODS

We conducted a national, prospective test-negative case-control study at thirteen PAEDS-FluCAN network hospitals contributing paediatric RSV data. From April 2024 to November 2025, hospitalised children with RSV-associated acute respiratory infection (ARI; cases) and contemporaneous RSV-negative controls were recruited. Immunisation effectiveness was estimated using a test-negative design with multivariable regression, adjusted for prespecified covariates, and calculated as (1-adjusted odds ratio) × 100% with 95% confidence intervals (CIs). Impact was assessed as the 2024-2025 change in the cumulative number of RSV hospitalisations during epidemiological weeks 14-48, excluding hospitals in two states with comprehensive 2024 nirsevimab programs, and stratified by age group.

FINDINGS: Between 1 January and 30 November 2025, 3743 children were recruited (2719 RSV-positive cases; 1024 test-negative controls). Overall effectiveness against RSV-associated ARI hospitalisation in the RSV-MIPP newborn cohort (born from 17 February) was 82·6% (95% CI: 70·6, 89·7). Effectiveness estimates for maternal vaccination and nirsevimab were 81·5% (68·4, 89·2) and 89·6% (73·6, 95·9) respectively. Nirsevimab effectiveness in the catch-up cohort (born 1st October 2024-16th February 2025) was 89·6% (66·4, 96·8). The program's impact, based on a single preprogram comparison year and excluding 2 states, was associated with 43·8%, 20·1% and 8·5% reduction in hospitalisations in infants aged 0-<3 months, 3-<6 months and 6-12 months respectively.

INTERPRETATION: These first southern hemisphere estimates of a hybrid RSV prevention program demonstrated high effectiveness against RSV hospitalisation over a single season. Longitudinal evaluation of the RSV-MIPP is needed to understand sustained effectiveness and year-round population level impacts.

FUNDING: This work was sponsored by the Australian Government Department of Health, Disability and Ageing and the Australian Centre for Disease Control.