Fig. 5: OTS-228 is significantly attenuated in vitro and not transmitted in vivo.
a, Schematic representation of the deleted polybasic cleavage site in OTS-228 spike compared to WT and OTS-206. b, Reduced plaque sizes were observed with PCS deletion (n = 10 plaques measured per group). c, Infection of hNECs and hBECs with indicated viruses (n = 3 biologically independent samples, one experiment). Infectious particle titres were assessed over time, confirming attenuation of OTS-228 in both cell lines. Data are presented as mean ± s.e.m. d, Attenuation experiment in Syrian hamsters (M. auratus, male, 9 weeks old) with OTS-228 over 21 dpv. Data obtained from OTS-228-inoculated hamsters (n = 10) and naïve contact animals (n = 4) from one experiment. Overview created with BioRender.com. e,f, Full attenuation of OTS-228 in terms of survival (e) and body weight changes (f) of vaccinated and contact hamsters (1–5 dpv n = 10; 6–21 dpv n = 5; 1–21 dpv n = 4 contacts). g, OTS-228 was not transmitted to naïve direct contact hamsters (0, 1, 2, 3, 4, 5 dpv n = 10; 7, 12, 16, 21 dpv n = 5; 0, 2, 3, 4, 5, 7, 12, 16, 21 dpv n = 4 contacts). h, High genome loads were detected in conchae samples of the inoculated animals at 5 dpv but low genome loads in the lung samples, especially at later timepoints. i,j, Analysed serum samples confirmed lack of transmission to contacts (i), highlighting a partly cross-neutralizing antibody response (j). Statistical significance was assessed using two-sided, two-way ANOVA with Tukey’s multiple-comparisons adjusted P values (95% CI) (b and c). Violin plots in b, g and h show individual samples with mean values (middle lines).
