Background
Three respiratory syncytial virus (RSV) prevention products were approved by the Therapeutic Goods Administration (TGA) and became available for use in 2024. The RSV vaccines Arexvy and Abrysvo were approved in adults ≥60 years, with Abrysvo also approved for pregnant women. The RSV monoclonal antibody Beyfortus was approved for neonates, infants, and children <24 months of age with specific risk conditions.

Process
Expanded safety surveillance of RSV prevention products was implemented by the TGA in 2024. Adverse events following immunisation (AEFI) reports to the TGA and dose administrations recorded in the Australian Immunisation Register (AIR) were systematically reviewed. Expanded surveillance included increased frequency of disproportionality analyses, lower signal thresholds, review of AEFI and reporting rates, monitoring AEFI of special interest, and consideration of global reports to the World Health Organization’s VigiBase. Notifications from pharmaceutical companies, international regulators, and AusVaxSafety were also reviewed.

Analysis
During 2024 there were 68 AEFI reports for Arexvy, 3 for Abrysvo, and 62 for Beyfortus. Cumulative reporting rates for these 3 products were 147, 47 and 102 reports per 100,000 doses, respectively. The most frequently reported reactions were generally expected, listed within their relevant Product Information documents, and consistent with global AEFI reports. Safety signals of urticaria and product administration error for Beyfortus were identified. Although there were no Australian reports, Guillain-Barre Syndrome was identified as a safety signal for Arexvy and Abrysvo based on post-marketing surveillance data in the United States. Inadvertent administration to pregnant women was identified as a safety signal for Arexvy.

Conclusions
Expanded safety surveillance in 2024 played an important role in the timely detection and investigation of potential safety signals for new RSV prevention products. This surveillance provides a solid foundation for continued monitoring in 2025 when national usage of RSV prevention products is anticipated to increase further.

Respiratory syncytial virus (RSV) prevention in Victoria in 2025 comprises three newly introduced products: a long-acting monoclonal antibody for infants, and vaccines targeted to pregnant women and older adults. Phase IV post-licensure safety surveillance is essential to confidently describe the benefit-risk profile of these products, but no single data source captures the full spectrum. We describe the development of comprehensive real-world RSV safety surveillance in Victoria.

Methods
We combined passive surveillance reporting of adverse events following immunisation (AEFI) and secondary use of administrative health datasets to assess AEFI associated with RSV immunisation at all levels of healthcare:
-Spontaneous reporting (SAEFVIC)
-Immunisation records linked to emergency department presentations, hospital admissions, notifiable conditions and mortality records for the whole Victorian population (Vaccine Safety Health Link, VSHL)
-General practice immunisation and diagnosis data from practices in Victoria and NSW (SAFESIG-GP)
-Victorian emergency department presentations and Nurse on Call (telehealth) calls related to immunisation, identified using natural language processing of triage notes (SynSurv-AEFI)

Key case definitions and epidemiological measures were harmonised across data sources, with additional metrics developed where individual data sources can address AEFI of concern (eg. pregnancy outcomes in VSHL). Analysis involves description of the safety profile, comparison against background rates and other vaccines, and rapid cycle analysis for signal detection for each product.

Results
Information derived from each data source (updated daily, weekly, or monthly) feed dynamically into a single consolidated report.
At 28 February, three weeks into the RSV program, vaccination error was the most frequent report to SAEFVIC (n=10, 43% of reports). SynSurv-AEFI identified four emergency department presentations within 24 hours of presentation, demonstrating the system’s potential for rapid signal detection.

Conclusion
Surveillance utilising multiple data sources across the healthcare spectrum overcomes limitations with individual data sources to provide essential timely intelligence, informing the safety of new immunisation programs.

Nirsevimab (Beyfortus®, AstraZeneca/Sanofi Pasteur) is a single dose long-acting monoclonal antibody designed to prevent serious respiratory syncytial virus (RSV) illness among infants entering their first RSV season and at-risk children entering their second RSV season. Clinical trial data reported a favourable safety profile of nirsevimab, however real-world data on adverse events following immunisation (AEFI) is limited.

From 2 April to 30 September 2024, the Western Australian Department of Health offered nirsevimab to all children born on or after 1 October 2023 entering this first RSV season as well as Aboriginal or medically-at-risk children born on or after 1 October 2022 entering their second RSV season. The Western Australian Department of Health used post-licensure safety surveillance to capture adverse events following nirsevimab through passive surveillance (Western Australian Vaccine Safety Surveillance (WAVSS) system), data linkage case finding, and two participant-based active surveillance surveys (Smartvax and REDCap).

WAVSS received 24 AEFI reports; 17 (71%) were co-administered with other routine immunisations, and 14 (58%) were reported via active surveillance. No serious AEFI were identified as being due to nirsevimab.

Smartvax surveillance, with a response rate of 27% (n=1,240), reported a reaction rate of 23% (n=284) with 2% (n=21) reported medical attendance (visit to a GP, emergency department, or called a helpline). None sought medical attention from a nurse or was admitted to a hospital.

The REDCap newborn survey, with a response rate of 23% (n=1,113), reported a reaction rate of 5% (n=47) with no reported medical attendance. Data linkage case finding resulted in 6 reports to WAVSS, with no concerning AEFI identified that may be related to nirsevimab.

The most commonly reported reaction across all surveillance methods were common and expected AEFI including rash, injection site reaction, fever, and gastrointestinal issues. Western Australia’s universal prophylaxis to newborns and young children found nirsevimab to be safe and well tolerated.

Understanding the short-term safety of vaccines administered during pregnancy is essential for guiding public health recommendations. We assessed the short-term safety of dTpa, influenza, and COVID-19 vaccines*, including their concomitant administration to pregnant women aged 15–49 years, who received these vaccines between 1 January 2023 and 30 September 2024 at participating general practices in AusVaxSafety. Online surveys soliciting adverse events following immunisation (AEFI) were sent three days post-vaccination. Demographic and vaccination data were retrieved from general practice records.
Among the 5,548 pregnant women (median age 32 years [IQR 29–35]) who responded to the survey, 81.8% received a single vaccine, while 18.2% received two or more vaccines on the same day. Most received dTpa (51.9%), influenza (26.8%), or both (14.6%). 90% were in their second or third trimester. Overall, 1,335 (24%) respondents reported at least one AEFI within three days post-vaccination, highest for COVID-19 vaccines alone (44%) or with other vaccines (48%) and lowest for influenza alone (16%). The most frequently reported symptoms were local pain (21%), fatigue (14%), myalgia (9.8%), and headache (8.9%). Medical attendance was reported by 0.5% of respondents, with 0.2% visiting an emergency department. Older age groups (≥25 vs. <25 years) reported slightly higher AEFI proportions for dTpa (26% vs. 16%) and influenza vaccines (16.9% vs. 9.9%). Those with underlying medical conditions reported higher AEFI proportions across most vaccine groups (35% vs. 23%). Impact on daily activities were reported in 4.4% of dTpa recipients, 3.4% of influenza recipients, 6.0% of those receiving both, 7.6% of COVID-19 vaccine recipients, and 17% of those receiving COVID-19 with other vaccines.
These findings provide an important baseline of short-term safety of maternal vaccination as new vaccines continue to be introdcued into the maternal vaccination program.

(*) RSV vaccines will be included if data allow at the time of presentation.

BACKGROUND
The World Health Organization has identified vaccine hesitancy as an emerging threat to public health, and the spread of misinformation throughout the COVID-19 pandemic has severely impacted vaccine confidence. Concerns about the safety of vaccination in pregnancy is hindering their uptake, and although there is reassuring evidence for singleton pregnancies, to date there are no studies that have examined their uptake and safety amongst women carrying a multiple pregnancy. This is important because compared to singleton pregnancies, multiple pregnancies carry a higher baseline risk of adverse outcomes for both the mother and infant, and a higher morbidity and mortality burden from respiratory infections. We aimed to calculate whether there was an increased risk in stillbirth, preterm birth or small for gestational age (SGA) infants among women who received influenza and pertussis vaccines in twin pregnancies compared to unvaccinated twin pregnancies.

METHODS
Study design: Data linkage using whole of Queensland and Northern Territory population registered births between 2012-2017. We identified twin pregnancies from perinatal data collections and dates of vaccinations from immunisation registers. We used gold-standard data analysis methods recommended for maternal vaccination safety studies, and national birthweight percentile charts specific for Australian-born twins to accurately reflect risk among SGA infants. We used Cox proportional-hazard models to calculate the risk of adverse birth outcomes, with maternal vaccination status as the time-varying exposure.

RESULTS
There were n=11,945 infants derived from 5,921 unique multiple pregnancies. Most women were unvaccinated (73%). We found no statistically significant increased risk of any adverse pregnancy or birth outcome between women that received a maternal influenza and/or pertussis vaccination and unvaccinated pregnant women. This remained consistent in our models after adjustment for known and potential confounders. We also found a borderline reduced risk of SGA infants among women who received pertussis vaccination in pregnancy.

PUBLIC HEALTH IMPORTANCE
Our study provides robust and novel evidence that addresses a critical gap in maternal vaccination safety research. Importantly, we provide reassurance to healthcare providers and pregnant women that maternal vaccinations do not increase the risk of stillbirth, preterm births or SGA infants in multiple pregnancies.

Introduction
Mastitis, a condition predominantly affecting women, causes pain, swelling, and redness and can be lactational or non-lactational. In 2022, mastitis was flagged as being disproportionately reported with COVID-19 vaccines to the Therapeutic Goods Administration’s (TGA) Australian Adverse Event Management System (AEMS) database. This led to a joint investigation between the TGA and Victoria’s vaccine safety surveillance system SAEFVIC.

Methods
As part of the TGA investigation, mastitis reports post-COVID-19 vaccination were analysed as of January 2023. Reporting rates were calculated using Australian Immunisation Register dose data, with disproportionality analysis conducted locally and internationally. The regulatory landscape and published literature were also reviewed.
SAEFVIC analysed a large de-identified general practice (GP) dataset- POLAR (Population Level Analysis and Reporting) to identify consultations for a new mastitis diagnosis between 1 January 2021 and 31 October 2024. Using a self-controlled case series (SCCS) design, the relative incidence of mastitis 1–28 days post COVID-19 vaccination was calculated. Analysis was further stratified by vaccine type and sex.

Results
The AEMS database had 51 reports of mastitis following COVID-19 vaccination. The TGA’s investigation found supportive evidence of an association between mRNA vaccines (Comirnaty® and Spikevax®) and mastitis and found no such evidence for Vaxzevria®.

The SCCS analysis found an increased risk of mastitis presentation in the 1-28 days following any COVID-19 vaccination (RI 1.63, 95%CI 1.39, 1.91 p<0.001) and specifically following mRNA vaccines (Comirnaty® and Spikevax®) (RI 1.74, 95%CI 1.48, 2.04 p<0.001) and females (RI 1.85, 95%CI 1.53, 2.24 p<0.001).

Conclusion
This collaborative investigation utilised regulatory spontaneous and jurisdictional surveillance, adverse event following immunisation reporting data and GP presentation data to detect and confirm a previously unrecognised adverse event and strengthen vaccine safety surveillance. It led to updates in product information documents for Comirnaty® and Spikevax® to include ‘mastitis’ as a potential vaccine-associated adverse event.

Background
Vaccines save lives, but all is not fair between the sexes. Clinical trials frequently aggregate safety results across all sexes and post-licensure surveillance relies on equitable reporting of adverse events (AE) and SMS survey responses, leaving sex differences in access to safe vaccination underinformed.

Methods
We reviewed 52,262 AE reports to Victoria’s vaccine safety surveillance system (SAEFVIC) from January 2020–2025 and considered sex-specific imbalances as reporting rates (RR) per 100,000 doses compared as ratios (RRR). We interrogated social media (X, formerly Twitter) using previously validated machine-learning topic modelling to identify vaccine-related reproductive-health mentions and compared with reported reactions.

Results
More AE reports were received for females than males (RRR 1.8, 95%CI 1,77–1.84), with disproportionality peaking at 40-49 years, and diminishing after 70 years of age. Reproductive biology alone did not account for differences as just 2.21% of adults reported reproductive-health-related reactions.

While expected sex-aligned signals of female vulval ulcers and male myo-pericarditis predominance were evident, many other AE had significant sex-imbalanced reporting rates. For reactions with count >10, 81 had >3.0 RRR for females and just 8 for males: only some with plausible clinical explanation.

The overall proportion of adult males self-reporting (10.9%) was two-thirds that of females, but conversely 25% more likely to be serious AE (20.2%, p<0.0001), suggesting surveillance captures only the tip of the iceberg of males' experiences.

These findings were affirmed by social media analysis identifying similar female vaccine-associated concerns, but several notable ones for males: notably swollen testicles, persistent erections and prostate cancer.

Conclusion
Females experience a wider range of vaccine adverse events than males and males appear to under-report. This underlines the importance of adjunctive active surveillance methodologies—including social media and large database analyses—to ameliorate these risks and create opportunities to redress inequities in safe vaccination and disease protection.