Comirnaty-Elicited and Convalescent Sera Recognize Different Spike Epitopes.

Area of Science:

• Immunology
• Virology
• Structural Biology

Background:

• Approved SARS-CoV-2 vaccines utilize a stabilized spike protein.
• The immune response to stabilized spike may differ from native spike during infection.

Purpose of the Study:

• To compare antibody recognition of SARS-CoV-2 spike protein epitopes between vaccinated and convalescent individuals.
• To investigate antibody diversity elicited by natural infection versus vaccination.

Main Methods:

• Peptide array analysis of antibody binding.
• Comparison of antibody profiles from Comirnaty-vaccinated, convalescent, and control sera.
• Mapping identified epitopes to pre- and post-fusion spike protein structures.

Main Results:

• 37 linear epitopes on the SARS-CoV-2 spike protein were identified.
• 26 epitopes were predominantly recognized by convalescent sera.
• Many convalescent-specific epitopes are masked in the pre-fusion spike structure, including three in the central helix exposed only in the post-fusion conformation.

Conclusions:

• Convalescent sera exhibit higher diversity in recognizing SARS-CoV-2 spike protein epitopes.
• Differences in epitope exposure between native and stabilized spike proteins may explain varied immune responses.
• Findings suggest potential implications for the breadth of immune response and vaccine design.