Broadly Protective Antibody-Like Vaccines Against Highly Pathogenic Coronaviruses.

Area of Science:

• Virology
• Immunology
• Vaccine Development

Background:

• Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) are highly pathogenic and contagious coronaviruses.
• Existing SARS-CoV-2 vaccines face challenges with ongoing spread, and no FDA-approved vaccines are available for MERS-CoV, necessitating novel vaccine strategies.
• The receptor-binding domain (RBD) is a key target for neutralizing antibodies (nAbs) against coronaviruses.

Purpose of the Study:

• To develop and evaluate novel bivalent vaccines targeting both SARS-CoV-2 and MERS-CoV.
• To assess the immunogenicity and efficacy of different bivalent vaccine constructs in a preclinical model.

Main Methods:

• Generation of three bivalent IgG1 Fc-fusion vaccines (BiVaxs) incorporating SARS-CoV-2 (Omicron variant) and MERS-CoV RBDs.
• Vaccine constructs included BiVaxFc-Native, BiVaxFc-Reverse, and BiVaxFc-FcRn (engineered for enhanced neonatal Fc receptor binding).
• Immunogenicity was assessed in mice, measuring IgG and nAb responses after vaccination.

Main Results:

• BiVaxFc-FcRn demonstrated significantly higher immunogenicity compared to other constructs in mice.
• BiVaxFc-FcRn induced robust IgG and nAb responses against MERS-CoV RBD after two doses and moderate responses against Omicron SARS-CoV-2 RBD after three doses.
• Remarkably, BiVaxFc-FcRn generated strong cross-reactive antibodies against SARS-CoV-1.

Conclusions:

• MERS-CoV RBD appears to be more immunogenic than Omicron SARS-CoV-2 RBD in this bivalent vaccine platform.
• The BiVaxFc-FcRn vaccine exhibits high potential as a broad-spectrum vaccine candidate.
• This platform could offer protection against targeted coronaviruses and potentially emerging viral threats.