A Candidate DNA Vaccine Encoding the Native SARS-CoV-2 Spike Protein Induces Anti-Subdomain 1 Antibodies

Area of Science:

• Virology
• Immunology
• Vaccine Development

Background:

• Broadly protective vaccines require antibodies targeting conserved viral epitopes.
• Understanding vaccine-induced polyclonal antibody responses is crucial for designing effective vaccines.
• B-cell epitopes of vaccine-induced antibodies against SARS-CoV-2 remain poorly defined.

Purpose of the Study:

• To identify unique antibody targets associated with neutralization breadth against SARS-CoV-2 variants.
• To investigate the correlation between antibody profiles and neutralization efficiency.
• To inform the rational design of broadly protective SARS-CoV-2 vaccines.

Main Methods:

• Combined neutralizing antibody functional assays with B-cell epitope mapping.
• Analyzed polyclonal antibody profiles in SARS-CoV-2 vaccinated rabbits.
• Assessed neutralization efficiency against different SARS-CoV-2 variants of concern (VOCs).

Main Results:

• Distinct polyclonal antibody profiles correlated with varying neutralization efficiencies against VOCs.
• Rabbits with intermediate and high cross-neutralization targeted fewer spike protein antigenic sites.
• A specific epitope in subdomain 1 (SD1), outside the receptor binding domain (RBD), was identified as a key target.

Conclusions:

• Targeting specific non-RBD epitopes, like SD1, can enhance functional antibody responses for broad protection.
• The developed approach can identify cross-neutralizing epitopes for future viral vaccine design.
• Findings support a strategy focusing on targeted antibody responses and non-RBD epitopes for SARS-CoV-2 vaccine development.