Objective:

To evaluate neutralization responses to SARS-CoV-2 variants and understand the structural and functional variations in antibody recognition.

Approach:

• Neutralisation Assays: Utilized a pseudovirus-based luciferase reporter assay to assess neutralization responses across different cohorts and variants.
• Cohort Analysis: Included plasma samples from naturally infected, vaccinated, and vaccinated-infected individuals.
• Computational Analysis: Conducted epitope prediction, antigenicity profiling, structural modeling, and docking simulations of CR3022 with variant RBDs.

Key Findings:

• Neutralisation responses varied by cohort and viral variant, with vaccinated individuals showing higher neutralisation titres.
• B.1.617.2 and B.1.1.529 variants exhibited reduced susceptibility to neutralisation by infection-elicited antibodies.
• Computational analyses revealed variant-associated differences in predicted antigenicity and epitope landscapes within the RBD and NTD.

Interpretation:

The study integrates experimental and computational approaches to characterize SARS-CoV-2 variant-specific neutralisation.

Limitations:

• The study does not establish a direct mechanistic relationship between structural changes and neutralisation susceptibility.
• Findings are based on specific cohorts and may not be generalizable to all populations.

Conclusion:

This research provides insights into differences in antibody responses across SARS-CoV-2 variants.