Nucleoside-modified RBD-mRNA protected mice from MERS-CoV infection and the protection was correlated with neutralizing antibodies. Mice were immunized I.D. with LNP-encapsulated nucleoside modified RBD-mRNA (10 μg/mouse) or empty-LNP control, and boosted twice at 4 weeks. Sera collected 10 days after the last immunization were tested for MERS-CoV S1-specific IgG antibodies (Abs) by ELISA (A) and neutralizing Abs (NT50) against infection of pseudotyped MERS-CoV (EMC2012 strain) in Huh-7 cells (B). One month after the last immunization, mice were transduced with Ad5/hDPP4, and then challenged with MERS-CoV (EMC2012 strain) (5 × 103 PFU/mouse). Lungs were collected three days after challenge, and viral titer was detected from the challenged mice, which are reported as PFU/g of tissues (C). The data are presented as mean ± s.e.m. of five mice in each group. *** (P < 0.001) indicates significant difference between RBD-mRNA-PseudoU and the control group. The experiments were repeated twice, resulting in similar results.