The Lancet Healthy Longevity · Nov 3, 2026

Frailty as a determinant of mRNA vaccine efficacy

By Vijayan VV, Nair PG, Sheela UB et al.

Frailty, an age-related state of increased vulnerability, is associated with greater susceptibility to infection and impaired vaccine response. In this Review, we examine how frailty-associated immunosenescence, including altered haematopoiesis, chronic inflammation, and dysfunction of innate and adaptive immune responses, can affect the immunogenicity, efficacy, and safety of lipid nanoparticle mRNA vaccines. Evidence from COVID-19 lipid nanoparticle mRNA vaccines and other vaccines suggests that people living with frailty can mount weaker or less durable responses than non-frail peers, although findings remain heterogeneous and frailty-specific evidence is scarce. The high customisability of lipid nanoparticle mRNA platforms creates opportunities for frailty-tailored vaccination. We discuss optimisation of lipid nanoparticle composition, targeting and dosing, mRNA cargo and combination-vaccine approaches, alongside host-directed measures addressing comorbidities, nutrition, and immune dysfunction. Integrating frailty into vaccine design, evaluation, and deployment could support safer, more effective, and more individualised vaccination strategies for older adults.

doi.org/10.1016/j.lanhl.2026.100930Open accessPubMed 42976900Interventions