mRNA vaccine expressing enterovirus D68 virus-like particles induces potent neutralizing antibodies and protects against infection

Enterovirus D68 (EV-D68) causes respiratory illness in children. It also causes severe paralysis called acute flaccid myelitis (AFM), which has become a global health threat. Here, we generated an mRNA vaccine expressing virus-like particles (VLPs) of EV-D68. We found that the mRNA vaccine elicited potent neutralizing antibodies against EV-D68 in the blood, and the neutralizing titer was superior to that of the inactivated whole virion (IWV) vaccine. The mRNA vaccine showed protective effects against intranasal challenge with EV-D68, and antisera from the vaccinated mice prevented the paralysis caused by EV-D68 infection in neonatal mice. Moreover, the mRNA vaccine induced neutralizing antibodies in the respiratory tract, which is the entry site for EV-D68. Additionally, it attenuated infection with coxsackievirus B3 (CVB3), which belongs to another enterovirus group, via CD8⁺ T cell responses. In conclusion, our results suggest that this mRNA vaccine is a promising candidate for EV-D68 prevention.