In this proof-of-concept study, mice were immunized with a vaccine candidate obtained by purification and ultraviolet-irradiation of adenovirus 36 (Ad36), which is associated with obesity. 14 weeks after subsequent injection of live Ad36, unvaccinated mice had 17% greater body weight and 20% more epididymal fat than vaccinated mice. Serum levels of proinflammatory cytokines and infiltrated immune cells in fat tissue were also decreased in vaccinated compared with unvaccinated mice.