Early first season measured impact results from UK’s bivalent RSVpreF vaccination program among adults aged 75–79 years are consistent with reported VE results from real-world studies employing diverse designs, indicating that if reliable vaccine uptake estimates are available, population-level impact can be inferred from well-designed, dedicated VE studies. While there was a broad range in the EOS1 bivalent RSVpreF VE estimates identified for this analysis (i.e., 67–91%), the documented impact in the UK RDD analyses corresponds with predicted impact based on these VEs. Several factors likely contributed to this variability in VE estimates (e.g., duration of post-vaccination follow-up, inclusion of specimen salvage, vaccine exposure data quality, and outcome definitions).

We directly estimated 76% and 91% VE from the published impact and uptake data from England and Scotland, respectively. Stability in vaccine coverage across evaluation periods likely contributed to variability in the calculated VEs, as Scotland’s coverage reached 52% in early September, and was roughly 69% throughout the study period [13], while England’s was dynamic, rising from 35% to 47% during November 2024 to January 2025 [11]. Consistent with this, we estimated 76% VE from the English impact results when using the longer evaluation period (through February), compared to an earlier estimate provided by the RDD authors (72% [11]), which used a shorter time period ending in early January with lower vaccine uptake and impact was reported.

Differences in each nation’s operationalization of the JCVI recommendations contributed to the differences in uptake across settings [13]. For example, timing of vaccine program implementation may have facilitated initial rapid uptake in Scotland, as rollout occurred in August 2024, prior to the September start of influenza/COVID-19 clinics [15]. In England, rollout was in September 2024, and at that time advice was not to co-administer RSV with COVID-19 or influenza vaccines if possible [16], so separate appointments had to be accommodated, which may have led to slower rate of uptake. Despite this, substantial population-level impact has been demonstrated in the UK RDD analyses, not only because of the high effectiveness of bivalent RSVpreF but also because of the notable uptake among eligible individuals within months of implementation in the national immunization program.

In contrast to the UK, vaccine uptake in the US has been less robust. The CDC’s National Immunization Survey reports that coverage with any RSV vaccine during the second season of implementation reached 48% by April 2025 among adults 75 years and older, and 38% among those 60–74 years of age [17]. Notably, these NIS uptake data are for all available RSV vaccines, of which there are three in the US (bivalent RSVpreF, RSVpreF3, and mRNA-1345), and rely on self-report, which is prone to recall bias. Uptake may be closer to that estimated based on claims data, which shows that through February 2025, 16.4% of US adults 60 years and older had received an RSV vaccination, with higher uptake of 23.3% among 75–59 year olds [18]. Efforts to expand US vaccination uptake in recommended populations could boost the nationwide population impact of the vaccination program.

The potential for demonstrating the impact on reducing RSV hospitalizations through these modelled estimates has implications for both public health and economic analyses. In England and Scotland, which together represent 92% of the UK’s population aged 75 years or older, an estimated 16,920 RSV-attributable respiratory hospitalizations occur annually in this age group; vaccinating all those ≥ 75 years, could potentially prevent ~ 12,000–15,000 of these annual hospitalizations in the first post-vaccination season [19]. However, as a recent study suggests, the annual burden of RSV hospitalizations in UK adults aged ≥ 75 years may in fact be 2.5 times higher when adjustments for key sources of underascertainment have been taken into consideration [20], expected impact could be higher. In June 2025 the UK updated its advice to additionally now include all adults aged ≥ 80 years and all older adults in care homes (regardless of age) in its RSV immunization program [21]. Emerging insights into RSVPreF VE therefore suggest a high proportion of all older UK adult RSV hospitalizations can potentially now be prevented once this advice is implemented. Improving and optimizing RSV vaccine uptake in older UK adults will be critical. Bivalent RSVpreF’s pivotal phase 3 study has demonstrated the vaccine confers multiple years of protection; its VE waned only 12.5% from 88.9% to 77.8% from season 1 to season 2 after vaccination [22]). On this basis, it is expected that even more hospitalizations would be prevented across subsequent seasons.

This analysis is subject to limitations. While another study has used a similar relationship between effectiveness and uptake to report RSV impact [11], this simplified approach does not take into account indirect effects of vaccination, variability in impact by subgroups (e.g., characteristics of the underlying population), nor change in VE over time (e.g., waning), or viral circulation dynamics, and should be viewed as an early look into the potential impact of this newly implemented RSV program. With few exceptions, VE studies and the UK impact analyses relied on standard-of-care testing for RSV; this incomplete population-level RSV testing led to underestimated incidence in these studies. Further, all studies relied on single-specimen testing for RSV, which has been shown to miss nearly half of RSV detections in adults [23]. The impact results from the UK did not include a full RSV season, though these likely represent a conservative estimate of the full seasonal impact of bivalent RSVpreF. Additionally, the included VE studies differed with respect to methodologies (including study design, patient characteristics, endpoints) and we did not account for this heterogeneity. Hospitalization VE estimates limited to those ≥ 75 years were not available for bivalent RSVpreF specifically from all studies; in some settings where they were available for combined VE estimates against both protein subunit vaccines by age, these estimates were very similar [24], however in others, bivalent RSVpreF VE for younger persons was lower compared to older persons [25], or vice versa [26]. This variability may have been due to the underlying age distribution of the studied populations, with smaller proportions of specific age categories generating unstable estimates. Finally, to ensure comparability between endpoints used in the UK impact and various VE studies, only RSV hospitalization endpoints were included, as such, evaluation of other important outcomes (medically attended visits, critical illness) was not assessed.