Immune response to mRNA vaccines targeting stable parts of the coronavirus

Novel mRNA-based vaccines targeting conserved domains of SARS-CoV-2 were designed with 70%-80% efficiency.

• The vaccines encoded conserved viral elements, including the spike S2 subunit and NSP3 Macrodomain I.
• In vitro characterization demonstrated 60%-80% cell survival alongside efficient antigen expression.
• Immunization in BALB/c mice resulted in strong antibody responses, particularly against S2 and Mac I, sustained for up to 84 days post-booster.
• Minimal antibody responses were observed for PLpro, potentially due to low stability or immunogenicity.
• Combinatorial lipid nanoparticles maintained robust antigen expression and comparable immune responses despite reduced dosing.
• The targeted antigenic regions showed high sequence conservation among major SARS-CoV-2 variants.

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