Introduction

Influenza is a viral illness responsible for an estimated 1 billion cases globally, including 3–5 million severe cases and 290 000–650 000 death [1, 2]. In France, from the 2011–2012 to the 2021–2022 seasons, seasonal influenza resulted in over one million community-based medical consultations, in an excess of 20 000 hospitalisations, and 9000 deaths per season [3]. Adults aged 65 years and above and residents of nursing homes, experience the highest burden of severe outcomes [4–7]. In France, seasonal influenza vaccination is recommended for vulnerable individuals, including those aged 65 and above, those with comorbidities aged 6 months-65 years, residents of nursing homes and pregnant women [8]. The estimated coverage rate among nursing home residents was 87% for the 2022–2023 season. During the 2022–2023 season, which lasted 19 weeks, 313 influenza clusters were reported in French in nursing homes. This number rose to 531 clusters (2023–2024) and 1490 (2024–2025) [9–11].

A key driver of this vulnerability is immunosenescence, the age-related decline in immune function characterised by reduced B- and T-cell responses and impaired vaccine-induced immunity [12]. This phenomenon can impair vaccine-induced immunity and may reduce the effectiveness of influenza vaccines [13]. To address this challenge, a high-dose (HD) influenza vaccine containing four times the antigen content of standard-dose (SD) vaccines (60 μg per strain vs. 15 μg) was developed and approved for use in France in 2020 [14–16]. Evidence from randomised controlled trials and real-world studies has demonstrated superior protection of HD vaccine against laboratory-confirmed influenza and its complications, including hospitalisations for cardio-respiratory outcomes [15–18]. In a cluster randomised trial conducted in the United States, HD demonstrated a reduction in hospitalisations for respiratory illness by 12.7% (95%CI: 1.8–22.4) among nursing home residents compared to SD vaccine [19].

In France, HD vaccine was introduced in 2021–2022 and, while not initially prioritised in national guidelines, has been recommended by the French Society for Geriatric Medicine for preferential use over standard-dose formulations in individuals aged 65 years and older, particularly nursing home residents [20, 21]. We previously reported the nationwide relative vaccine effectiveness (rVE) of the HD versus SD vaccines among community-dwelling individuals aged 65 and over with a 23.3% (95%CI: 8.4–35.8) and 27.4% (19.8–34.3) reduction in influenza hospitalisations during the 2021–2022 and a 2022–2023 seasons [22, 23]. We present the exploratory analysis of the rVE of the HD versus SD vaccines against hospitalisations due to influenza, pneumonia and combined influenza/pneumonia in nursing home residents aged 65 and above during the 2022–2023 season in France.