Fig. 4: Increased potency of vaccine candidate S0* against VOC Omicron.

A nAb titres against prototypic and omicron spike-pseudotyped virus on day 28 after vaccination with two doses (day 0 and day 7) of prototype YF-S0 or YF-S0*. NAb titres against prototypic spike-pseudotyped virus (gray circles) are from Fig. 2A and D. Same sera were retested for Omicron spike-pseudotype virus (pink symbols). Red squares denote nAb titers for those animals included in the subsequent challenge study (see also Fig. S1). B Antigenic cartography. Cross-reactivity of sera raised by original S0 (gray squares) and updated S0* (orange squares) vaccine antigen against five different SARS-COV-2 variants (circles: prototype, gray; VOC Beta, blue; Gamma, orange; Delta, purple; Omicron, pink) plotted on a two-dimensional map41. NIBSC, human reference sample (NIBSC 20/130; red square). C–E, Viral loads in hamster lungs (C, D) and nasal wash (E) 4 days after infection with 105 TCID50 of VOC Omicron quantified by virus titration (C) and quantitative RT-PCR (D, E) (pink squares). VOC Omicron challenge was performed 7 weeks after vaccination, i.e., delayed by another 4 weeks compared to the previous standard schedule, using each n = 6 hamster vaccinated with YF-S0, YF-S0* or sham. Bar graphs denote median ± IQR. Dashed line represents the lower limit of quantification. Differences between groups were analyzed using nonparametric Kruskal–Wallis test uncorrected for ties.