Protective prototype-Beta and Delta-Omicron chimeric RBD-dimer vaccines against SARS-CoV-2

Area of Science:

• Vaccinology
• Virology
• Immunology

Background:

• SARS-CoV-2 variants pose a significant challenge to existing vaccine efficacy.
• Previous development of ZF2001, a protein subunit vaccine using dimeric receptor-binding domain (RBD) of the prototype SARS-CoV-2.
• The need for adaptable vaccine platforms to address rapidly emerging viral strains.

Purpose of the Study:

• To develop and evaluate a chimeric RBD-dimer vaccine approach for adapting to SARS-CoV-2 variants.
• To assess the immunogenicity and protective efficacy of prototype-Beta and Delta-Omicron chimeric RBD-dimer vaccines.
• To validate the potential of this strategy for creating updated, multivalent vaccines against circulating and emerging SARS-CoV-2 variants.

Main Methods:

• Design of prototype-Beta chimeric RBD-dimer to target the Beta variant.
• Immunization and challenge studies in mouse models using chimeric and homotypic RBD-dimer vaccines.
• Verification of protection in macaque models.
• Generalization of the approach to create a Delta-Omicron chimeric RBD-dimer vaccine.
• In vivo challenge studies with Delta or Omicron SARS-CoV-2 in mice.

Main Results:

• The prototype-Beta chimeric RBD-dimer vaccine demonstrated broader sera neutralization against SARS-CoV-2 variants compared to homotypic forms.
• This chimeric vaccine conferred improved protection in mice and was further validated in macaques.
• The Delta-Omicron chimeric RBD-dimer vaccine also showed broader neutralization and enhanced protection against both Delta and Omicron variants in mice.
• The chimeric approach proved effective in adapting immunogens to specific variants.

Conclusions:

• The chimeric RBD-dimer vaccine approach is a viable strategy for adapting to SARS-CoV-2 variants.
• This method elicits broader neutralization and improved protection against diverse variants.
• The findings support the development of variant-adapted, multivalent vaccines for enhanced pandemic preparedness against current and future SARS-CoV-2 strains.