Background: Influenza vaccine efficacy/effectiveness can vary from season to season due in part to the dominant circulating strains and antigenic matching. This study reviews the relative vaccine efficacy/effectiveness (rVE) of high-dose inactivated trivalent influenza vaccine (HD-IIV3) compared to standard-dose influenza vaccines (SD-IIV) in adults aged ≥ 65 years against influenza-associated outcomes. Additional sub-analyses of HD-IIV3 rVE were performed by the predominantly circulating influenza strain and the antigenic match or mismatch of the vaccine against the predominant circulating strains. Methods: An updated systematic review and meta-analysis was conducted for studies assessing the rVE of HD-IIV3 against probable/laboratory-confirmed influenza-like illness (ILI), hospital admissions, and death in adults aged ≥ 65 years. Results from individual seasons were extracted from the studies, and viral surveillance data were used to determine the dominant circulating strains and antigenic match for each season. Results were then stratified based on clinical outcomes and seasonal characteristics and meta-analyzed to estimate pooled rVEs of HD-IIV3. Results: 15 publications were meta-analyzed after screening 1,293 studies, providing data on 10 consecutive influenza seasons and over 22 million individuals receiving HD-IIV3 in randomized and observational settings. Across all influenza seasons, HD-IIV3 demonstrated improved protection against ILI compared to SD-IIV (rVE = 15.9%, 95% CI: 4.1–26.3%). HD-IIV3 was also more effective at preventing hospital admissions from all-causes (rVE = 8.4%, 95% CI: 5.7–11.0%), as well as influenza (rVE = 11.7%, 95% CI: 7.0–16.1%), pneumonia (rVE = 27.3%, 95% CI: 15.3–37.6%), combined pneumonia/influenza (rVE = 13.4%, 95% CI: 7.3–19.2%) and cardiorespiratory events (rVE = 17.9%, 95% CI: 15.0–20.8%). Reductions in mortality due to pneumonia/influenza (rVE = 39.9%, 95% CI: 18.6–55.6%) and cardiorespiratory causes (rVE = 27.7%, 95% CI: 13.2–32.0%) were also observed. Similar pooled rVEs were observed in both matched and mismatched seasons and in seasons where A/H3N2 or A/H1N1 strains were predominantly circulating. Conclusions: Evidence over 10 consecutive influenza seasons and in more than 34 million individuals aged ≥ 65 years suggests that HD-IIV3 is consistently more effective than SD-IIV at reducing influenza cases as well as influenza-associated clinical complications irrespective of circulating strain and antigenic match. A video summary of the article can be accessed here.
Elderly (65+) Administration Efficacy/effectiveness Influenza