A prespecified analysis of the randomised DANFLU-2 trial in Danish adults aged 65 and older found that relative effectiveness of high-dose versus standard-dose influenza vaccine against hospitalisation for influenza or pneumonia increased as frailty risk increased. The gradient was apparent when frailty was modelled continuously but not when participants were grouped into prespecified frailty categories, and subgroup estimates were imprecise with confidence intervals crossing the null. The signal supports considering higher-antigen vaccination in frail older adults while stopping short of confirmatory evidence.
Key Points
- Higher relative effectiveness of high-dose vaccine with increasing frailty risk
- Categorical frailty subgroups showed no clear effect modification
- Subgroup estimates imprecise; confidence intervals crossed the null
Longevity Analysis
Frailty is not merely a descriptor of ageing but a measurable modifier of how the body mounts and sustains an immune response, and this analysis quantifies that in a randomised setting. Immune competence declines unevenly across individuals of the same chronological age, which argues for stratifying preventive interventions by functional reserve rather than birth year. Preventing a single respiratory hospitalisation in a frail older adult protects muscle mass, mobility, and cognitive stability that are difficult to recover once lost, making the timing and dose of seasonal immunisation a durable rather than incidental decision.
Original published by The Lancet Healthy Longevity, by Caroline Espersen, Niklas D Johansen, Daniel Modin, Kira H Janstrup, Matthew M Loiacono, Rebecca C Harris, Youjun Huang, Carsten S Larsen, Lykke Larsen, Lothar Wiese, Michael Dalager-Pedersen, Brian L Claggett, Katja V Bartholdy, Katrine F Bernholm, Julie I-M H Borchsenius, Filip S Davidovski, Lise W Davodian, Maria Dons, Lisa S Duus, Frederik H Fussing, Anne Marie R Jensen, Nino E Landler, Adam C F Langhoff, Mats C H Lassen, Anne B Nielsen, Camilla I Ottosen, Morten Sengeløv, Kristoffer G Skaarup, Scott D Solomon, Martin J Landray, Gunnar H Gislason, Lars Køber, Pradeesh Sivapalan, Cyril J-M Martel, Jens U S Jensen, Kazumasa Harada, Gaetan Gavazzi, Tor Biering-Sørensen.