https://www.sciencedirect.com/science/article/pii/S2589004221014504
With the experiments presented earlier, we observed a high mortality rate among the mice inoculated with LNPs. These findings prompted us to perform a dose-response experiment to determine the amounts of LNPs that might be safe to use for mucosal vaccination. We intranasally inoculated adult WT B6 mice with LNPs ranging from 2.5 μg to 10 μg/mouse and monitored their health and weight for up to 8 days. We found that ∼80% of mice treated with 10 μg of LNP died in less than 24 h (Figure 3D). The 5 μg dose killed ∼20% of the mice by that time, whereas all the 2.5 μg-treated mice survived and showed no weight drop (Figure 3D) and no significant clinical signs of distress (Figure 3E). For the 5 and 10 μg doses, the surviving mice showed notable clinical scores of distress, such as shaking/shivering, and they lost weight significantly during the first 2 days of treatment (Figures 3E and 3F). After the first ∼3 days, these mice did not continue to show significant clinical scores anymore, and their weight slowly started to normalize (Figure 3E). These data suggest that careful optimization of the LNP dose might allow the use of the mRNA-LNP platform for intranasal vaccination.
https://www.sciencedirect.com/science/article/pii/S2589004221014504
With the experiments presented earlier, we observed a high mortality rate among the mice inoculated with LNPs. These findings prompted us to perform a dose-response experiment to determine the amounts of LNPs that might be safe to use for mucosal vaccination. We intranasally inoculated adult WT B6 mice with LNPs ranging from 2.5 μg to 10 μg/mouse and monitored their health and weight for up to 8 days. **We found that ∼80% of mice treated with 10 μg of LNP died in less than 24 h** (Figure 3D). The 5 μg dose killed ∼20% of the mice by that time, whereas all the 2.5 μg-treated mice survived and showed no weight drop (Figure 3D) and no significant clinical signs of distress (Figure 3E). For the 5 and 10 μg doses, the surviving mice showed notable clinical scores of distress, such as shaking/shivering, and they lost weight significantly during the first 2 days of treatment (Figures 3E and 3F). After the first ∼3 days, these mice did not continue to show significant clinical scores anymore, and their weight slowly started to normalize (Figure 3E). These data suggest that careful optimization of the LNP dose might allow the use of the mRNA-LNP platform for intranasal vaccination.
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