Lipid Nanoparticle RBD-hFc mRNA Vaccine Protects hACE2 Transgenic Mice against a Lethal SARS-CoV-2 Infection

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• The COVID-19 pandemic spurred mRNA vaccine development, establishing it as a key anti-SARS-CoV-2 immunization strategy.
• Preclinical models like hamsters and monkeys have limitations in fully assessing vaccine protective efficacy against SARS-CoV-2.
• A novel SARS-CoV-2 receptor-binding domain (RBD) conjugated to human Fc (RBD-hFc) mRNA vaccine, delivered via lipid nanoparticles (LNPs), was previously developed.

Purpose of the Study:

• To evaluate the protective efficacy of the RBD-hFc mRNA vaccine against SARS-CoV-2 challenge.
• To assess the immunogenicity and protective capabilities of the RBD-hFc mRNA vaccine in a relevant animal model.

Main Methods:

• Utilized the K18 human angiotensin-converting enzyme 2 (K18-hACE2) mouse model for SARS-CoV-2 infection studies.
• Administered the RBD-hFc mRNA vaccine formulated with LNPs to K18-hACE2 mice.
• Challenged vaccinated and control mice with a lethal dose of SARS-CoV-2 to assess survival and immune responses.

Main Results:

• RBD-hFc mRNA vaccination in K18-hACE2 mice elicited robust humoral immune responses, including significant binding and neutralizing antibodies.
• A notable 70% survival rate was observed in vaccinated mice following a lethal SARS-CoV-2 challenge.
• All control group animals succumbed to the infection, highlighting the vaccine's protective effect.

Conclusions:

• The RBD-hFc mRNA vaccine demonstrates significant protective efficacy against lethal SARS-CoV-2 infection in the K18-hACE2 mouse model.
• This study represents the first report of a nonreplicating mRNA vaccine conferring protection in K18-hACE2 mice against a lethal SARS-CoV-2 challenge.
• The findings support the potential of this mRNA vaccine platform for controlling SARS-CoV-2 and future viral threats.