Longitudinal Variations in Antibody Responses against SARS-CoV-2 Spike Epitopes upon Serial Vaccinations

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• The COVID-19 pandemic, caused by SARS-CoV-2, necessitated rapid vaccine development.
• mRNA vaccines (Pfizer/BioNTech) are effective but target specific viral regions.
• Viral evolution, particularly in the receptor-binding domain (RBD), drives immune evasion.

Purpose of the Study:

• To analyze humoral immune responses to a three-dose monovalent BNT162b2 mRNA vaccine regimen in naive individuals.
• To compare antibody responses across the entire SARS-CoV-2 spike glycoprotein (S).
• To identify novel epitopes that contribute to viral neutralization and inform future vaccine design.

Main Methods:

• Longitudinal study of nine previously uninfected individuals.
• Administration of a three-dose BNT162b2 mRNA vaccine regimen.
• High-throughput phage display (VirScan) to analyze anti-S antibody repertoire.

Main Results:

• Two vaccine doses induced the broadest and highest magnitude anti-S antibody responses.
• Identified novel, highly boosted non-RBD epitopes.
• These non-RBD epitopes correlated strongly with neutralization capacity.

Conclusions:

• Two-dose mRNA vaccination is highly effective in generating broad humoral immunity.
• Novel non-RBD epitopes represent promising targets for future vaccine development.
• Findings support the development of multi-valent vaccines and antiviral drugs.