MERS-CoV RBD-mRNA Presents Better Immunogenicity and Protection than the Spike-mRNA

Area of Science:

• Virology
• Immunology
• Vaccine Development

Background:

• Middle East respiratory syndrome coronavirus (MERS-CoV) poses a significant public health risk.
• The MERS-CoV spike (S) protein, particularly its receptor-binding domain (RBD), is crucial for viral entry and a key target for vaccine development.
• Direct comparative studies on the immunogenicity and efficacy of S- versus RBD-based MERS-CoV vaccines are lacking.

Purpose of the Study:

• To compare the immunogenicity, neutralizing activity, and protective efficacy of two mRNA vaccines targeting either the S protein (S-mRNA) or the RBD (RBD-mRNA) of MERS-CoV.
• To evaluate the durability of immune responses and protection conferred by these vaccines in a mouse model.

Main Methods:

• Two lipid nanoparticle (LNP)-encapsulated mRNA vaccines, S-mRNA and RBD-mRNA, were developed and administered to mice.
• Immunogenicity was assessed by measuring antibody titers and neutralizing activity against MERS-CoV strains and variants.
• Protective efficacy was evaluated in a middle-aged mouse model challenged with MERS-CoV.

Main Results:

• Both LNP-encapsulated mRNA vaccines exhibited stability across various temperatures.
• RBD-mRNA elicited significantly higher and more durable antibody responses compared to S-mRNA.
• RBD-mRNA demonstrated stronger and broader neutralizing activity against MERS-CoV and its variants, and provided durable protection against infection in mice.

Conclusions:

• LNP-encapsulated RBD-mRNA is a highly effective vaccine candidate against MERS-CoV.
• The RBD-mRNA vaccine shows significant potential for further development due to its superior immunogenicity, neutralizing capacity, and protective efficacy.