Extended Data Fig. 3. Safety study of OTS4-5, OTS7-8 and OTS-206 in Syrian hamster model.
a, Experimental setup of intranasal inoculation of Syrian hamsters (Mesocricetus auratus, male, 12 weeks old (WT, OTS4-5 and OTS7-8) and 8 weeks old (OTS-206) (Donors) (n=10 hamsters/OTS-group until 5dpi, n=5 hamsters/OTS-group until 21dpi, n=4 hamster WT-group until 5dpi) with OTS4-5, OTS7-8, or OTS-206 SARS-CoV-2, including co-housing of naïve contact animals (Contacts) (n=4 hamsters/group until 21dpi) 1 day post inoculation (dpi). Data obtained from two independent experiments (experiment 1 (OTS4-5, OTS7-8, WT) and experiment 2 (OTS-206). Overview created with BioRender.com. b, c, Body weight changes of inoculated and contact hamsters in percent as mean data (+/- SEM) and on individual level. d, e, Virus genome copy numbers in nasal washings of donor and contact hamsters. f, g, Virus genome copy numbers in the organ samples of donors at 5 and 21 dpi. h, Virus genome copy numbers in the organ samples of contact hamsters at 21 dpi. i, Serum samples of 5 and 21 dpi analyzed by SARS-CoV-2RBD-ELISA. j, Serum samples were additionally analyzed in live virus neutralization assay (capacity to neutralize 100 TCID50) against ancestral WT SARS-CoV-2. k, Pneumonia-induced pulmonary atelectasis 5 dpi given in % affected area. l, Histopathology, lung whole slide images showing atelectasis, hematoxylin-eosin stain. Scale bar, 2.5 mm. m, Virus antigen score, 0= no antigen, 1 = focal, 2 = multifocal, 3 = coalescing, 4 = diffuse. n, Representative virus antigen imaging (WT group) by immunohistochemistry (SARS-CoV nucleocapsid protein detection), mainly in type-1 pneumocytes, bar 100 µm. Statistical significance was assessed by two-sided, unpaired, nonparametric multiple t-test with Mann-Whitney test (compared ranks, CI: 95%) (panel b-h). *P<0.05, **P < 0.01, ***P<0.001, ****P<0.0001. No asterisk indicates no statistical significance.