Extended Data Fig. 10: Syrian hamsters' shows protection against XBB.1.5 Omicron challenge infection after a single intranasal OTS-228 vaccination.
a, Experimental setup. Syrian hamsters (Mesocricetus auratus, male and female equally mixed, 9 weeks old) were OTS-228 vaccinated and subsequently challenged by SARS-CoV-2 XBB.1.5, with co-housing of naive direct contact animals 1-day post-challenge (dpc). Data were obtained from n=16 hamsters/group, with n=6 naïve direct contact hamsters/group, comparing vaccinated to nonvaccinated. Overview created with BioRender.com. b, Body weight percentages of donor animals over time indicated no weight loss post-infection (dpc1-2: n=16/group, dpc3-5: n=11/group, dpc6-14 n=6/group). Data are presented as mean values +/- SEM. c, Body weight percentage of contact animals over time showed weight loss following co-housing (n=6). d, Relative survival post-challenge (n=6/group), with one unrelated death and its contact animal excluded from comparisons (see Supplementary Fig. 7). e, RT-qPCR analysis of donor hamster nasal washing samples for SARS-CoV-2 viral genomes revealed reduced shedding for the OTS-228 vaccinated group (dpc1-2: n=16/group, dpc3-5: n=11/group, dpc6-14 n=6/group). f, RT-qPCR analysis of contact hamster nasal washing samples for SARS-CoV-2 viral genomes indicated positive results for most animals (n=6/group). g, RT-qPCR analysis for SARS-CoV-2 viral genomes of organ samples from donor animals euthanized at 2 dpc (n=5/group) showed reduced viral loads in OTS-228 vaccinated animals. h, RT-qPCR analysis for SARS-CoV-2 viral genomes of organ samples from donor animals euthanized at 5 dpc (n=5/group) demonstrated pronounced virus clearance in the OTS-228 group. i, RT-qPCR analysis for SARS-CoV-2 viral genomes of organ samples from donor hamsters euthanized at 14 dpc (n=6/group) showed reduced viral loads in vaccinated animals. j, RT-qPCR analysis for SARS-CoV-2 viral genomes of organ samples from contact hamsters euthanized at 14 dpc (n=6/group) revealed no differences between groups. k, SARS-CoV-2RBD-ELISA of serum from donor and contact animals confirmed positive reactions in all vaccinated animals’ post-vaccination. l, Virus neutralization test (VNT100) against homologous WT SARS-CoV-2 verified detectable neutralization at 19 dpv and post-challenge (dpv19: n=16/group, dpc2: n=5/group, dpc5: n=5/group, dpc14: n=6/group). m, Virus neutralization test (VNT100) against SARS-CoV-2 variant Omicron XBB1.5 showed lower and delayed neutralizing immune responses compared to the ancestral virus. Statistical significance was assessed by two-sided, unpaired, nonparametric multiple t-test with Mann-Whitney test (compared ranks) (panel b, c, e-j, l and m). *P<0.05, **P < 0.01, ***P<0.001, ****P<0.0001. No asterisk indicates no statistical significance.
