Highlights
– A national multicentre test‑negative study in England reports an overall vaccine effectiveness (VE) of 82.3% (95% CI 70.6–90.0) for a bivalent RSV pre‑F vaccine against RSV‑associated hospital admission in adults aged 75–79 years.
– VE was high against severe disease requiring oxygen (86.7%) and against clinical presentations including lower respiratory tract infection (88.6%) and exacerbations of chronic lung and heart disease (77–79%).
– Effectiveness persisted in people with immunosuppression (72.8%), supporting vaccination in frail and medically complex older adults; further data on durability and broader age groups are needed.
Background
Respiratory syncytial virus (RSV) has long been recognised as an important cause of acute respiratory illness in older adults, where it can precipitate severe lower respiratory tract infection, decompensation of chronic cardiopulmonary disease, and frailty‑related complications leading to hospitalisation. Recent development of vaccines targeting the prefusion conformation of the F (fusion) protein—so‑called pre‑F vaccines—has generated promise for preventing severe RSV disease in older populations. England introduced a targeted RSV immunisation programme using a bivalent pre‑F vaccine for older adults from Sept 1, 2024. While vaccine efficacy and safety data from clinical trials have supported regulatory approvals, real‑world effectiveness against the spectrum of clinical presentations that drive hospital admissions—particularly exacerbations of chronic conditions—has been less well described.
Study design
The study by Symes et al. used a multicentre, test‑negative, case‑control design embedded within the Hospital‑based Acute Respiratory Infection Sentinel Surveillance (HARISS) network across 14 hospitals in England. Key features:
- Population: adults aged 75–79 years eligible for the vaccine who were admitted with acute respiratory infection (ARI) for ≥24 hours between Oct 1, 2024, and Mar 31, 2025.
- Case definition: molecular detection of RSV on nasopharyngeal or combined nose‑and‑throat swab collected within 48 hours of admission.
- Controls: patients admitted with ARI testing negative for RSV, influenza, and SARS‑CoV‑2.
- Exposure ascertainment: vaccination status and sex obtained from the National Immunisation Information System; clinical data by structured questionnaire.
- Primary outcome: RSV‑associated hospital admission; secondary analyses addressed disease severity and clinical presentations such as lower respiratory tract infection (LRTI), pneumonia, and exacerbation of chronic heart or lung disease, and subgroup analyses included immunosuppressed patients.
The test‑negative design (TND) is commonly used for vaccine effectiveness (VE) studies of respiratory pathogens to reduce biases related to healthcare‑seeking and testing practices: both cases and controls sought care for similar respiratory illness and were systematically tested.
Key findings
Of 1,006 eligible older adults admitted with ARI during the surveillance period, 173 were RSV positive (cases) and 833 were RSV negative (controls). Demographics were similar between groups: 52.3% female overall, and mean age ~77.7 years.
Main vaccine effectiveness estimates (adjusted):
- VE against hospitalisation for any RSV‑associated ARI: 82.3% (95% CI 70.6–90.0).
- VE against severe disease requiring oxygen supplementation: 86.7% (75.4–93.6).
- VE against admission with lower respiratory tract infection including pneumonia: 88.6% (75.6–95.6).
- VE against hospitalisation attributed to exacerbation of chronic lung disease: 77.4% (42.4–92.8).
- VE against exacerbation of chronic heart disease, lung disease, and/or frailty: 78.8% (47.8–93.0).
- VE in immunosuppressed individuals: 72.8% (39.5–89.3).
Collectively, these results indicate strong protection against clinically meaningful endpoints that drive hospital resource use in older adults, including prevention of severe hypoxaemia and destabilisation of chronic cardiopulmonary disease.
Clinical and public health interpretation
This real‑world evidence supports that the bivalent RSV pre‑F vaccine substantially reduces the risk of RSV‑associated hospital admission in the studied age group and confers protection against severe disease and against presentations characterized primarily by exacerbations of chronic disease. From a clinical perspective, these findings are important because RSV in older adults often presents not only as primary viral pneumonia but also as a trigger for worsening heart failure, COPD exacerbations, and functional decline—events that carry high morbidity, mortality, and healthcare costs.
Key implications include:
- Vaccination should be considered an effective intervention to prevent RSV‑related hospitalisation in eligible older adults, including those with chronic cardiopulmonary comorbidities and immunosuppression.
- Prevention of exacerbations may reduce both acute morbidity and downstream healthcare utilisation, including oxygen therapy and possibly length of stay.
- Programs targeting older age cohorts can have immediate clinical impact during RSV seasons and should be accompanied by monitoring of uptake, equity, and safety in frail populations.
Strengths
- Laboratory‑confirmed outcomes and use of the TND reduce bias from differential healthcare seeking and testing.
- Integration with a national immunisation registry improved exposure ascertainment and minimized misclassification of vaccination status.
- Granular clinical categorisation permitted assessment of vaccine performance against disease presentations most relevant to older adults (LRTI, chronic‑disease exacerbations, severe hypoxaemia).
Limitations and considerations
While the findings are compelling, several limitations temper interpretation and guide next steps:
- Age range: the study was restricted to 75–79‑year‑olds; extrapolation to younger older adults (65–74) or those ≥80 years requires caution because immunosenescence and frailty profiles differ.
- Surveillance setting: sentinel hospitals may not be fully representative of all hospitals or community settings; the sample may under‑represent or over‑represent certain socioeconomic groups or care home residents.
- Residual confounding: despite registry linkage, unmeasured confounders (health‑seeking behaviour, functional status) might influence VE estimates.
- Seasonality and viral evolution: data cover a single RSV season; VE durability across subsequent seasons and against potential antigenic shifts requires ongoing evaluation.
- Safety: this effectiveness study did not report adverse event rates; safety signals remain primarily derived from prelicensure trials and post‑marketing surveillance.
Expert commentary and mechanistic plausibility
Vaccines targeting the prefusion conformation of the RSV F protein elicit high titers of neutralising antibodies that block viral entry, offering a biologically plausible mechanism for the observed protection. The bivalent formulation likely broadens antigenic coverage, which may contribute to the strong VE across clinical phenotypes. Clinicians should interpret these results in the context of individual patient risk: older adults with chronic cardiac or pulmonary disease, prior hospitalisation for respiratory illness, or immunosuppression are likely to derive substantial absolute benefit.
Practical recommendations
- Offer the RSV pre‑F vaccine to eligible older adults per national guidance, with prioritisation of those with chronic cardiopulmonary conditions and immunosuppression.
- Ensure robust record linkage between immunisation registries and hospital surveillance to monitor real‑world VE and safety.
- Counsel patients that the vaccine reduces the risk of hospitalisation and severe disease, while continuing to emphasise other preventive measures (e.g., respiratory hygiene during peak seasons).
- Conduct further evaluations of VE durability, impact on mortality and ICU admission, and performance in other age strata and care settings such as care homes.
Conclusion
Symes et al. provide timely and clinically relevant evidence that a bivalent RSV pre‑F vaccine introduced into England’s older adult immunisation programme substantially reduces RSV‑related hospital admissions in adults aged 75–79 years, including severe disease and exacerbations of chronic heart and lung disease. The protective effect observed in immunosuppressed individuals bolsters recommendations for vaccination in medically vulnerable groups, while highlighting the need for continued surveillance to assess duration of protection, safety in frail cohorts, and effectiveness across different seasons and age bands.
Funding
This surveillance and analysis were supported by the UK Health Security Agency.
References
Symes R, Whitaker HJ, Ahmad S, Arnold D, Banerjee S, Evans CM, Gore R, Hart J, Heaney K, Kon OM, Melhuish A, Ortale Zogaib M, Pelosi E, Rahman NM, Woltmann G, McKeever T, Zambon M, Watson CH, Lim WS, Lopez Bernal J; HARISS network collaborators. Vaccine effectiveness of a bivalent respiratory syncytial virus (RSV) pre‑F vaccine against RSV‑associated hospital admission among adults aged 75–79 years in England: a multicentre, test‑negative, case‑control study. Lancet Infect Dis. 2025 Oct 27:S1473‑3099(25)00546‑8. doi: 10.1016/S1473‑3099(25)00546‑8. Epub ahead of print. Erratum in: Lancet Infect Dis. 2025 Nov 6:S1473‑3099(25)00683‑8. doi: 10.1016/S1473‑3099(25)00683‑8. PMID: 41167207.