The investigation of mRNA vaccines formulated in liposomes administrated in multiple routes against SARS-CoV-2.

COVID-19 pandemic has resulted in an unprecedented global public health crisis. It is obvious that SARS-CoV-2 vaccine is needed to control the global COVID-19 public health crisis. Since obvious advantages including fast manufacturing speed, potent immunogenicity and good safety profile, six mRNA vaccines have been used to prevent SARS-CoV-2 infections in clinic with lipid nanoparticles (LNP) formulation via intramuscular injection. In this work, we first constructed RBD-encoding mRNA (RBD-mRNA) formulated in liposomes (LPX/RBD-mRNA) and investigated the influence of administration routes on the immunogenicity. LPX/RBD-mRNA can express RBD in vivo and successfully induced SARS-CoV-2 RBD specific antibodies in the vaccinated mice, which efficiently neutralized SARS-CoV-2 pseudotyped virus. Moreover, the administration routes were found to affect the virus neutralizing capacity of sera derived from the immunized mice and the types (Th1-type and Th2-type) of cellular immune responses. This study indicated that liposome-based RBD-mRNA vaccine with optimal administration route might be a potential candidate against SARS-CoV-2 infection with good efficacy and safety.