Sex-dependent impairment of antibody responses to tick-borne encephalitis virus vaccination and infection in obese mice.

Obesity is a growing global health concern with profound effects on immune function and vaccine efficacy. This study investigated the impact of obesity on immune responses to tick-borne encephalitis virus (TBEV) vaccination and infection using a mouse model. Mice on a high-fat diet (HFD) exhibited increased body weight, fat mass and a pre-diabetic state compared to standard chow diet (SCD) controls. After vaccination with the TBEV vaccine (Encepur), HFD mice showed significantly lower TBEV-specific IgG litres and neutralizing antibody levels compared to SCD mice. Splenocyte counts per organ mass were significantly higher in vaccinated SCD mice compared to their HFD counterparts, correlating with the elevated IgG litres observed in the SCD group. These results underscore the critical role of diet in shaping the immune response and vaccine efficacy. Following TBEV infection, HFD mice did not display increased disease severity or elevated viral litres in the serum, spleen or brain relative to SCD controls, indicating that obesity did not exacerbate viral replication or dissemination. However, a sex-dependent effect of obesity on the humoral immune response was observed. Male HFD mice produced antibody litres comparable to their SCD counterparts, suggesting minimal impact of obesity on their immune response. In contrast, female HFD mice exhibited significant impairments in TBEV-specific IgG and neutralizing antibody production compared to female SCD mice, as well as both male HFD and male SCD groups. These findings highlight a complex interplay between obesity, sex and immune function, with obesity disproportionately impairing the immune response after TBEV vaccination and infection.