Identification of an Optimized Receptor-Binding Domain Subunit Vaccine against SARS-CoV-2

Area of Science:

• Virology
• Immunology
• Vaccine Development

Background:

• Current SARS-CoV-2 vaccines target the whole spike protein.
• The receptor-binding domain (RBD) is key for neutralizing antibodies, responsible for 90% of serum activity.

Purpose of the Study:

• To develop and evaluate an optimized RBD-based subunit vaccine for SARS-CoV-2.
• To assess immunogenicity and efficacy in mouse models, including protection against viral challenge.

Main Methods:

• Constructed and tested various RBD versions with different adjuvants (aluminum hydroxide, DDA/TDB).
• Utilized human angiotensin-converting enzyme 2 knock-in mice for in vivo efficacy studies.
• Assessed neutralizing antibody and CD4 T cell responses.

Main Results:

• Subdomain 1 (SD1) is crucial for RBD immunogenicity; mammalian cell-produced RBDSD1 showed superior results.
• RBDSD1 combined with DDA/TDB adjuvant elicited stronger immune responses than aluminum hydroxide.
• RBDSD1Fc significantly enhanced immunogenicity and neutralizing antibody titers.
• The Beta version of RBDSD1Fc offered cross-neutralization against variants, including Omicron.
• Beta RBDSD1Fc with DDA/TDB provided complete protection in knock-in mice.

Conclusions:

• An optimized RBDSD1Fc subunit vaccine, particularly the Beta version with DDA/TDB adjuvant, is highly immunogenic and protective.
• This RBD-based vaccine candidate is suitable for further clinical development against SARS-CoV-2 variants.