Dual impact of squalene-adjuvanted influenza vaccine on immunity and glucose homeostasis in obese mice

Abstract Obesity is a known risk factor for impaired immune responses and reduced vaccine efficacy. Individuals with obesity-related metabolic disorders face heightened vulnerability to influenza, underscoring the urgent need to optimize vaccine strategies for this population. We investigated the immunological and metabolic outcomes of different influenza vaccine formulations in a diet-induced obese (DIO) mouse model. Specifically, we compared the effects of high-dose versus squalene-adjuvanted vaccines on humoral immunity, protection against viral challenge, and glucose metabolism. High-dose vaccination failed to induce robust virus-specific antibodies or sustain long-lived plasma cells in the bone marrow following infection. In contrast, squalene-adjuvanted vaccines significantly enhanced antibody responses and conferred superior protection. However, this immune enhancement was accompanied by aggravated hyperglycemia in obese mice, indicating a potential immunometabolic trade-off. Adjuvanted influenza vaccines may improve immune efficacy in obesity, but at the cost of worsening glycemic control. These findings highlight the importance of personalized vaccination approaches that account for metabolic status and immunometabolic interactions in vulnerable populations.