Figure 1. The Omicron SARS-CoV-2 variant exhibits strong immune-escape that is overcome by booster vaccination.

(a) Diagrams of SARS-CoV-2 S variants used for pseudotyping, which indicate the location of specific mutations as well as the S1 and S2 subunits of S, the N-Terminal Domain (NTD), Receptor Binding Domain (RBD), Fusion Peptide (FP), and Trans-membrane domain (TM). (b) Infectivity of pseudotyped viruses produced in parallel for infection of HEK293T cells stably expressing ACE2. (c) Infectivity of pseudotyped lentivirus in human lung epithelia-derived CaLu-3 cell line. Bars in b and c represent means +/− standard deviation, and significance is determined by one-way ANOVA with Bonferroni’s multiple testing correction. Results of at least 3 independent experiments are averaged and shown. (d) Sera from 48 HCWs collected 3–4 weeks after second mRNA vaccine dose was used to neutralize pseudotyped virus for variants, and the resulting 50% neutralization titers (NT₅₀) are displayed. (e) Sera from 23 HCWs following homologous mRNA booster vaccination were assessed for nAb titers. (f) Sera from 9 ICU COVID-19 patient samples and 9 hospitalized non-ICU COVID-19 patient samples collected in 2020 prior to the approval of any SARS-CoV-2 vaccines were assessed for nAb titers. (g) Sera from 19 ICU COVID-19 patient samples collected during the Delta-wave of the pandemic were assessed for nAb titers. Mean NT₅₀ values in panels d-g are displayed at the top of plots along with relative neutralization sensitivity with D614G set to 100%; bars represent mean +/− standard error, and significance relative to D614G is determined by one-way ANOVA with Bonferroni’s multiple testing correction. (h) Heat maps showing patient/vaccinee NT₅₀ values against each variant. Patient/vaccinee numbers are identified as P for Pfizer/BioNTech BNT162b2 vaccinated/boosted HCW, M for Moderna mRNA-1273 vaccinated/boosted HCW, I for ICU patient samples collected during the 2020 D614G-wave, H for hospitalized non-ICU patient samples collected during the 2020 D614G-wave, or D for ICU patient samples collected during the Delta-wave. P-values are represented as *p < 0.05, **p < 0.01, ***p < 0.001; ns, not significant.