Retrospective Neutralization Analysis of SARS-CoV-2 Variants in Early Pandemic Sera

• Retrospective analysis examining neutralizing antibody responses in serum from 100 individuals who were vaccinated and boosted.
• Standardized cell-culture and in vitro neutralization assays were used to test sera against the original Wuhan-Hu-1 spike and major variants of concern: B.1.351, B.1.617, and B.1.1.529/Omicron.
• The investigation also assessed potential antibody-dependent enhancement (ADE) in monocyte-derived macrophages.

• Overall, only 61% of serum samples neutralized the Wuhan-Hu-1 variant.
• Among these Wuhan-Hu-1 neutralizers, 20.6% demonstrated cross-neutralization of both B.1.351 and B.1.617.
• Of the cross-neutralizers, 66.6% were capable of neutralizing Omicron (B.1.1.529) as well.
• ADE was observed in 1% of the samples.

• Individuals with both prior infection and vaccination exhibited stronger neutralizing responses than those who were only vaccinated and boostered.

• The study provides retrospective, real-world context on how immune responses in this cohort diverged from early expectations.
• Limitations include reliance on a specific vaccinated/boosted population and the use of in vitro assays, with no extrapolated clinical outcomes provided.

Explicit uncertainty and limitations are acknowledged within the study's framework.

• The findings underscore the need for ongoing reassessment of vaccine strategies in light of viral evolution and variable cross-neutralization profiles.