Fig. 2. A vaccine based on updated spike antigen S0* offers protection against four VOCs.

A nAb titres against prototypic (gray circles), VOC Beta (blue circles), VOC Gamma (orange circles) and VOC Delta (purple circles) spike-pseudotyped virus on day 21 after vaccination with prototype YF-S0. Numbers above individual violin plots indicate animals seroconverted. Red datapoint indicates the NIBSC 20/130 human reference sample. NAb titres against prototypic spike-pseudotyped virus (gray circles) are from Fig. 1B. B Neutralization curves for NIBSC 20/130 human reference sample against same set of pseudotyped viruses. C Schematic of the updated YF-S0* (S0*) vaccine candidate based on VOC Gamma, plus three extra stabilizing proline residues. Vaccination scheme with YF-S0*. Syrian hamsters were immunized twice intraperitoneally with 10⁴ PFU of S0* (n = 24 vaccinated and n = 24 sham vaccinated) on day 0 and 7 and inoculated intranasally on day 24 with 10³ median tissue-culture infectious dose (TCID50) of either VOC Alpha (green triangles), VOC Beta (blue squares), VOC Gamma (orange triangles), and VOC Delta (purple circles). D nAb titres against prototypic, VOC Beta, VOC Gamma, and VOC Delta spike-pseudotyped virus on day 21 after vaccination with YF-S0*. Numbers above individual violin plots indicate animals seroconverted. Red datapoint indicates the NIBSC 20/130 human reference sample. E, F Viral loads in hamster lungs 4 days after infection (n = 6 each YF-S0* or sham vaccinated per variant) quantified by quantitative PCR with reverse transcription (RT-qPCR) (E) and virus titration (F). G cumulative lung pathology scores from H&E-stained slides of lungs for signs of damage. H Representative H&E-stained images of sham- or S0*-vaccinated hamster lungs after challenge. Perivascular inflammation (black arrows) with focal endothelialitis (green arrows); peribronchial inflammation (blue arrows); patches of bronchopneumonia (red arrows); scale bar upper row images 100 µm, lower row images 50 µm. 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.