Extended Data Fig. 6: OTS-206 show comparable efficacy to mRNA-vaccines and inducing long-term immunity in K18-hACE2 mice.
a, K18-hACE2 transgenic mice (7–15 weeks old, n=8 mice/group) were immunized (prime & boost) either intramuscularly with a single dose of 1 μg of mRNA-Vaccine Spikevax (Moderna), or intranasally with 5’000 PFU of OTS-206. b, During immunization, mice were regularly monitored for body weight changes. Each line in the body weight loss graphs represents a mouse. Six days post-challenge, mice were euthanized and organ samples were collected for evaluation of infectious virus titers, viral genome copy numbers, and pathology. At 57 dpi a group of mice was intranasally inoculated with 104 TCID50 of SARS-CoV-2D614G, or SARS-CoV-2 Delta VOC (c-h). The rest of the immunized mice were kept for approximately 5 months and then intranasally inoculated with 104 TCID50 of SARS-CoV-2D614G (i-n). d, j, Infectious virus titers from the brain samples were determined using plaque assays in VeroE6 cells. e, k, Genome copy numbers (genome equivalence per ml, gEq/mL) in nose, lung, brain, olfactory bulb, and oropharyngeal swab samples of mice infected with different viruses were quantified using probe-specific RT–qPCR. f, l, High level of long-term protection was confirmed by histopathological scores for lung pathology. Data obtained from one experiment. g, m, Immunohistochemical analysis specific for SARS-CoV-2 nucleocapsid protein (magnification 50x). Scale bar, 500 µm. h, n, Sera collected on 6 dpc (post-challenge) were tested against SARS-CoV-2 Wuhan WT virus in a serum neutralization test. Data obtained from one experiment. Infectious viral particle concentrations, genome copies, immunohistochemical analysis and individual body weights in Extended Data Fig. 6 and Supplementary Fig. 6e and f). Body weight changes, clinical scores, and histopathological scores in Supplementary Table 6. Statistical significance was determined using two-sided, two-way ANOVA (Tukey’s multiple comparison test) (panels c, and i,) or ordinary one-way ANOVA (panels f, and l,) or by using two-sided, unpaired nonparametric t-test (Mann Whitney test) (panels d, e, j and k). No asterisk indicates no statistical significance. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.
