Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants

Virus-like particle (VLP) and live virus assays were used to investigate neutralizing immunity to Delta and Omicron SARS-CoV-2 variants in 239 samples from 125 fully vaccinated individuals. In uninfected, non-boosted individuals, VLP neutralization titers to Delta and Omicron were reduced 2.7-fold and 15.4-fold, respectively, compared to wild-type (WT), while boosted individuals (n=23) had 18-fold increased titers. Delta breakthrough infections (n=39) had 57-fold and 3.1-fold titers whereas Omicron breakthrough infections (n=14) had 5.8-fold and 0.32-fold titers compared to uninfected non-boosted and boosted individuals, respectively. The difference in titers (p=0.049) was related to a higher proportion of moderate to severe infections in the Delta cohort (p=0.014). Correlation of neutralizing and spike quantitative antibody titers was decreased with Delta or Omicron compared to WT. Neutralizing antibodies in Delta and Omicron breakthrough infections increase overall, but the relative magnitude of increase is greater in more clinically severe infection and against the specific infecting variant.