Outer membrane vesicle increases the efficacy of an influenza vaccine in a diet-induced obese mouse model

Abstract

Obesity has been associated with increased symptoms and mortality in influenza patients and impaired immune responses to the influenza vaccine. To date, however, there is no effective adjuvant to improve vaccine efficacy for the obese population. To address this issue, we generated a modified outer membrane vesicle with attenuated endotoxicity (fmOMV) and tested its adjuvant effect on the influenza vaccine in comparison with a squalene-based oil-in-water adjuvant (AddaVax) using a diet-induced obese (DIO) mouse model. Although coadministration of fmOMV did not affect neutralizing antibody (Ab) response, it preferentially induced IgG2c antibody response and significantly increased the vaccine-induced T cell response. More importantly, fmOMV conferred significant protection against homologous and heterologous influenza virus challenge, whereas AddaVax showed marginal protection irrespective of the strongest Ab and T cell responses in DIO mice. These results indicate that fmOMV improves the antigen-specific T cell response and the efficacy of an influenza vaccine, suggesting a potential influenza vaccine adjuvant for the obese population.

Keywords: Adjuvant; Influenza; Obesity; Outer membrane vesicles; Protective immunity; Vaccine.