Australian real-world data show vaccination during pregnancy provides strong protection against RSV hospitalisation, particularly during babies’ first months of life.
Vaccinating pregnant women against RSV cut the risk of their babies being hospitalised with the virus by around 80% in the first year of Australia’s national maternal vaccination program, researchers have found.
The Australian multicentre study found the bivalent RSV prefusion F protein vaccine (RSVpreF) was 77.8% effective against hospitalisation for RSV lower respiratory tract disease (LRTD) in infants from birth to six months of age.
Protection was greatest when babies were youngest, reaching 86.3% during the first two months of life and 80.2% from birth to three months. Effectiveness was 68.2% among infants aged older than two months through four months, although the confidence intervals for the age-specific estimates overlapped.
The researchers said the findings were particularly relevant because the most severe RSV outcomes and hospitalisations occur during the first three months of life. RSV remains the leading global cause of lower respiratory tract disease in infants.
“In this test-negative case-control study of 1012 hospitalised infants, maternal RSVpreF vaccination was associated with 78% to 81% reduction in RSV-associated hospitalisation from birth through six months of age, with the highest vaccine effectiveness in earliest age intervals,” they wrote.
“Vaccine effectiveness was consistent across stratifications by gestational age at vaccination, vaccination to delivery time interval, and proximal administration with other vaccines during pregnancy and was demonstrated for both RSV-A and RSV-B.”
Australia added RSVpreF to the National Immunisation Program in February 2025, with vaccination recommended from 28 weeks’ gestation as the primary year-round strategy for protecting infants up to six months of age.
All states and territories also fund the monoclonal antibody nirsevimab for infants who are not protected through maternal vaccination and for high-risk infants regardless of maternal vaccination status.
The findings, published in JAMA Pediatrics, came as RSV continued its reign as Australia’s most frequently notified major respiratory virus this year.
National Communicable Disease Surveillance Dashboard data accessed on 25 August show 117,425 RSV notifications had been recorded nationally, compared with 98,569 laboratory-confirmed influenza notifications and 64,393 covid-19 notifications.
NSW recorded the most RSV notifications at 50,934, followed by Victoria with 24,022 and Queensland with 21,345. There were 8478 notifications in Western Australia, 7781 in South Australia, 2118 in Tasmania, 1807 in the ACT, and 940 in the Northern Territory.
The surveillance data also show a markedly higher burden of RSV than pertussis. There had been 6430 pertussis notifications nationally by 25 August.
The Australian setting offered the researchers an opportunity to assess effectiveness across different patterns of RSV circulation. While RSV generally peaks from April to September in temperate southern states, it circulates throughout the year in tropical and northern parts of the country.
For the primary analysis, maternal vaccination was defined as RSVpreF given from 28 weeks’ gestation and at least 14 days before delivery. Of the 1012 infants admitted with acute respiratory illness, 655 met the definition for LRTD. Among these were 386 RSV-positive cases and 269 RSV-negative controls.
Only 114 of the 386 RSV-positive infants, or 30%, had mothers who received RSVpreF, compared with 171 of 269 RSV-negative controls, or 64%. The median gestational age at maternal vaccination was 31 weeks and the median age of infants hospitalised with LRTD was just 52 days. Three-quarters of these babies were three months old or younger.
The primary outcome of RSV-LRTD hospitalisation required infants to have cough or difficulty breathing as well as at least one sign including an increased respiratory rate, oxygen saturation below 95%, wheeze or crackles, chest wall indrawing or other signs of respiratory distress.
Severe LRTD included outcomes such as oxygen saturation below 90% requiring oxygen, high-flow oxygen or mechanical ventilation, ICU or high-dependency unit admission, or apnoea.
Maternal vaccination was 80.4% effective against hospitalisation for severe RSV-LRTD among infants up to six months of age and 80.8% effective against RSV-associated acute respiratory illness hospitalisation.
There were also differences in illness severity according to maternal vaccination status. Among all infants hospitalised with acute respiratory illness, 32% of the 499 infants born to unvaccinated mothers developed severe LRTD, compared with 17% of the 513 infants whose mothers had received RSVpreF.
Among the 655 infants hospitalised with LRTD, oxygen support was required in 27% of those born to vaccinated mothers compared with 44% of those born to unvaccinated mothers. ICU or high-dependency care was required in 9.1% and 13.2%, respectively.
Researchers found no clear evidence that protection differed according to when women were vaccinated within the recommended gestational window.
Related
Giving other recommended vaccines around the same time did not appear to substantially change RSVpreF effectiveness either, the researchers said.
Among vaccinated mothers of infants with LRTD, more than half had received another vaccine either on the same day as RSVpreF or within two weeks. Effectiveness against RSV-LRTD was 76.8% when another vaccine was administered within two weeks and 79.6% when the vaccines were given more than two weeks apart.
Protection also appeared similar against the two major RSV subtypes, with effectiveness of 89.4% against RSV-A and 87.4% against RSV-B. Sensitivity analyses were consistent with the main findings, with higher effectiveness point estimates during the RSV season.
The researchers said the results were broadly consistent with accumulating international real-world evidence, including findings from the UK, Argentina, and the US.
The Australian estimate of 80.4% effectiveness against severe RSV-LRTD hospitalisation through six months was slightly higher than the 70.0% efficacy against severe RSV-associated medically attended LRTD reported in the pivotal phase 3 MATISSE trial.
The researchers noted, however, that their study was restricted to hospitalised infants, while only 61.7% of infants with severe LRTD in MATISSE were hospitalised, which they said may partly account for the difference.
Limitations included the possibility of residual confounding from unmeasured factors affecting both maternal vaccination and infant RSV risk, as well as potential bias from changing RSV circulation during the first year of the program.
The researchers also acknowledged the possibility of maternal vaccination being misclassified despite using the Australian Immunisation Register and medical records. Incomplete or delayed documentation of nirsevimab use was another potential source of misclassification, while differences in testing and hospital admission practices could have introduced selection bias.
Despite this, they said the use of a nationally distributed hospital network, routine PCR testing, and verified maternal vaccination records strengthened the findings, while Australia’s mix of seasonal and year-round RSV circulation provided evidence from a different epidemiological setting to many previous real-world studies.
“These findings support the effectiveness of maternal immunisation as a key component of Australia’s RSV Maternal and Infant Protection Program, with the greatest benefit observed during the earliest, highest-risk months of life,” the researchers concluded.
“Ongoing longitudinal evaluation is warranted to monitor effectiveness over time within infant subgroups and by disease severity.”
