Impact of obesity on vaccine effectiveness against respiratory viral infections: from immunological mechanisms to clinical outcomes

Obesity is a major global health challenge associated with chronic low-grade inflammation, immune dysregulation, and increased susceptibility to severe respiratory viral infections. As obesity prevalence continues to rise, understanding its impact on vaccine-induced immunity has become increasingly important. This narrative review examines current evidence on the effects of obesity on vaccine immunogenicity, immune durability, and clinical effectiveness against influenza and coronavirus disease 2019 (COVID-19). Studies demonstrate that obesity has little effect on early humoral responses following influenza vaccination, whereas findings for COVID-19 vaccines are more heterogeneous and influenced by vaccine platform, obesity severity, prior infection, metabolic health, and follow-up duration. However, longitudinal evidence from both influenza and COVID-19 vaccine studies suggests that obesity, particularly severe obesity, is associated with accelerated antibody waning, reduced neutralizing activity, impaired memory B-cell and antigen-specific T-cell responses, and increased breakthrough infections despite initially adequate antibody titres. These alterations are driven by chronic inflammatory signaling, adipokine imbalance, impaired antigen presentation, germinal center dysfunction, accelerated B-cell senescence, T-cell metabolic inflexibility, insulin resistance, and dysregulated immunometabolism. Importantly, influenza and COVID-19 vaccines remain highly effective in reducing severe disease, hospitalization, and mortality among individuals with obesity, supporting continued vaccination in this population. Collectively, the available evidence indicates that conventional serological measures alone are insufficient to evaluate vaccine performance in obesity. Future studies should integrate assessments of antibody durability, neutralizing capacity, cellular immunity, and immune memory while considering obesity severity and metabolic phenotype as well as vaccine platform, vaccination stage, previous infection, and the timing of immune assessment to guide optimized vaccination strategies and booster schedules.