Enhanced variant neutralization through glycan masking of SARS-CoV-2 XBB1.5 RBD

Area of Science:

• Virology
• Immunology
• Vaccine Development

Background:

• SARS-CoV-2 exhibits continuous antigenic evolution due to immune pressure from infections and vaccinations.
• Emerging variants necessitate frequent and costly vaccine updates to maintain efficacy.
• Novel strategies are required to broaden vaccine protection and extend effectiveness.

Purpose of the Study:

• To investigate antigen modification as a strategy to enhance vaccine-induced immune responses against SARS-CoV-2.
• To introduce a glycosylation site into a non-neutralizing epitope of the SARS-CoV-2 XBB.1.5 receptor binding domain (RBD).
• To redirect the immune response towards more potent neutralizing epitopes.

Main Methods:

• Modification of the SARS-CoV-2 XBB.1.5 RBD by introducing a glycosylation site into a specific epitope.
• Development of an mRNA vaccine platform utilizing the modified RBD antigen.
• Immunization of mice with the modified antigen vaccine.
• Assessment of neutralizing antibody titers and protection against a range of SARS-CoV-2 Omicron variants (BA.2 to JN.1).

Main Results:

• Immunization with the modified XBB.1.5 RBD mRNA vaccine resulted in a significant increase in neutralizing antibodies compared to the wild-type RBD.
• The modified antigen demonstrated superior protection against diverse SARS-CoV-2 Omicron variants, including BA.2 and JN.1.
• The glycan masking approach proved effective in enhancing the immunogenicity of the RBD.

Conclusions:

• Antigen modification, specifically through glycan masking, can effectively redirect immune responses towards conserved and potent neutralizing epitopes.
• The combination of glycan masking and mRNA vaccine technology offers a promising strategy for developing broader and more effective SARS-CoV-2 vaccines.
• This approach has the potential to address the challenge of evolving viral variants and reduce the cost associated with frequent vaccine updates.