Exosome-based delivery of VP1 protein conferred enhanced resistance of mice to CVB3-induced viral myocarditis.

Coxsackievirus B3 (CVB3) is an important cause of viral myocarditis with no vaccine available in clinic. Herein we constructed an exosome-based anti-CVB3 vaccine (Exo-VP1), and compared its immunogenicity and immunoprotection with our previously reported recombinant VP1 protein (rVP1) vaccine. We found that compared with the 25 μg rVP1 vaccine, Exo-VP1 vaccine containing only 2 μg VP1 protein induced much stronger CVB3-specific T cell proliferation and CTL responses (with an increase of more than 70% and 40% respectively), and elicited greater splenic Th1/CTL associated cytokines (IFN-γ, TNF-α and IL-12). Furthermore, higher IgG levels with increased neutralizing titers and avidity were also evidenced in Exo-VP1 group. Consistently, Exo-VP1 group exhibited enhanced resistance to viral myocarditis than rVP1 vaccine, reflected by reduced cardiac viral loads, improved myocardial inflammation and an increased survival rate. Collectively, we reported that Exo-VP1 might present a more potent CVB3 vaccine candidate than rVP1 vaccine.