Fig. 1: Immunization with NDV and MVA viral vectors encoding SARS-CoV-2 S protein protects K18-hACE2 transgenic mice challenged with SARS-CoV-2.
A Mouse efficacy schedule. Female K18-hACE2 transgenic mice (n = 10 mice/group) were immunized with homologous (MVA-S(3P)/MVA-S(3P) and NDV-HXP-S/NDV-HXP-S) or heterologous (MVA-S(3P)/NDV-HXP-S and NDV-HXP-S/MVA-S(3P)) prime/boost immunization regimens, as indicated. Mice received two doses with a 4-week interval (days 0 and 28), of 1 × 107 PFUs of MVA-S(3P) by the intramuscular (IM) route in 100 μL of PBS (50 μL/leg) or of 1 × 106 EID50 of NDV-HXP-S by the intranasal (IN) route in 50 μL of PBS. Mice inoculated with PBS were used as a control group. On days 14 post-prime and 26 post-boost (day 54; 2 days pre-challenge), serum samples were obtained from each mouse, as indicated. At day 56 (4 weeks post-boost) all mice were challenged intranasally with 1 × 105 PFUs of SARS-CoV-2 MAD6 isolate (ancestral Wuhan strain). At day 5 post-challenge, five mice per group were sacrificed and lungs, nasal washes (NW) and serum samples collected as indicated. Vaccinated mice were left until day 17 post-challenge, when spleens, lungs, NW and serum samples were collected. B, C The challenged mice were monitored for change of body weight (B) and mortality (C) for 17 days. †: mice were euthanized due to loss of more than 20% of initial body weight. D, E Virus replication in lung samples (D) and NW (E). SARS-CoV-2 subgenomic E and genomic RdRp mRNA detected by RT-qPCR at 5 days after SARS-CoV-2 virus infection. The geometric mean with geometric standard deviation (SD) of mRNA levels (in relative units normalized to uninfected mice) from duplicates of each lung sample and nasal wash for each group are represented. Limit of detection (LOD) = 100. F, G SARS-CoV-2 infectious virus in lung samples (F) and NW (G) at 5 days post-challenge. The geometric mean with geometric SD of live virus (PFUs/g of lung tissue or PFUs/mL of nasal wash) from triplicates of each sample for each group are represented. The dotted line represents the LOD. Ordinary one-way ANOVA of transformed data followed by Tukey’s multiple comparison test: **p < 0.002; ***p < 0.0002; ****p < 0.0001.
