This Pfizer-sponsored real-world retrospective non-interventional study will be conducted within a research network comprised of independent hospitals across Australia using data collected during routine standard of care clinical encounters available in health records, supplemented with information from the official national immunisation registry, the Australian Immunisation Register. Additional data from accredited pathology laboratories will be included. There will be no active enrollment of study participants, no direct contact with study participants, and no collection of any primary data outside of the standard of care.

This study will use a test negative design to evaluate real-world vaccine effectiveness of RSVpreF vaccination during pregnancy against RSV-associated outcomes in infants.

This case-control study using a test negative design will include all infants through 12 months of age who were admitted to one of the participating hospitals with symptoms of respiratory infection, met the clinical case definition of acute respiratory illness, and had a respiratory specimen collected within 10 days prior to hospital admission through 3 days after a hospital admission with an RSV test result through standard of care testing.

The primary objective is to estimate vaccine effectiveness (VE) of ABRYSVO during pregnancy against RSV-positive lower respiratory tract disease (LRTD) hospitalisation among infants from birth through 6 months (0 to ≤180 days) of age.

Baseline characteristics of the study population will be described by case/control status and by maternal RSVpreF vaccination status. Standardised mean differences may be used to compare the distributions (absolute differences >0.10 will be considered meaningful). For all VE objectives, we will use a logistic regression model to compare the odds of maternal ABRYSVO vaccination during pregnancy between test-positive cases and test-negative controls, generating an odds ratio (OR) and 95% CI and we will use multivariable logistic regression to compute an adjusted OR (aOR), from which we will derive final VE estimates, adjusted for potential confounding, according to the formula: VE = (1-aOR) x 100%.

Inclusion Criteria:

Participants must meet all of the following inclusion criteria to be eligible for inclusion in the study:

1. Infant ≤12 months (≤360 days) of age on the hospitalisation date.
2. Index date within the time period for data collection (approximately 01 March 2025 - 28 February 2027)
3. Hospitalised with acute respiratory illness meeting the protocol-defined clinical case definition, and for whom RSV testing results from a specimen collected 10 days prior to hospital admission through 3 days after a hospital admission are known.
4. Infant born to a birth mother eligible to receive ABRYSVO vaccination, with infant date of birth on or after 17 February 2025.

Exclusion Criteria:

Participants meeting any of the following criteria will not be included in the study:

1. Infant born at <28 weeks and 0/7 days of gestational age.
2. Infant received any licensed or investigational RSV preventive product (e.g., palivizumab, nirsevimab, active RSV vaccine) since birth.
3. Infant received ≥1 blood transfusion or other blood products containing antibody (e.g., fresh frozen plasma) since birth.
4. Infant born to a birth mother who received any other licensed or investigational RSV vaccine during this pregnancy.
5. Infant born to a birth mother for whom ABRYSVO vaccination status cannot be confirmed in available data sources.

This hospital-based retrospective study will be conducted in up to 9 hospitals across 6 states/territories in Australia, supported by the Paediatric Active Enhanced Diseases Surveillance Network.

Given the retrospective nature of this study, hospitals that already function as national sentinel units for respiratory virus surveillance, or have robust clinical, laboratory or epidemiological surveillance will be included. Each participating hospital conducts year-round standard of care testing for acute respiratory illness which includes respiratory virus panel test using PCR.

Study will include all infants through 12 months of age who were admitted to one of the participating hospitals with symptoms of respiratory infection, met the clinical case definition of acute respiratory illness, and had a respiratory specimen collected within 10 days prior to hospital admission through 3 days after a hospital admission with an RSV test result through standard of care testing.

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.