Live attenuated vaccination protects aged chimeric ACE2 mice from severe SARS-CoV-2 pathogenicity in vivo
Fig 6
SARS-CoV-2 infection results in high viral loads and severe disease in aged chACE2 mice.
Forty-six to fifty-five weeks old chACE2 mice were infected with 7x104 PFU of wt virus or LAVNsp16 in 30 µl PBS (n = 4). Mice were sacrificed on day 2 (n = 4) or day 4 (n = 5) postinfection. Weight loss (A) and clinical score (B) of all animals were determined over time and shown as mean + /- s.d.. C) Infectious viral titers in BAL and lung tissue of aged mice at day 2 postinfection were assessed by infection of Caco-2 cells followed by immunofluorescence analysis. Titers are shown as mean of triplicate infections + /- s.d. overlayed with data points of individual animals. (D) Viral genome copies BAL and lung tissue was determined by RT-qPCR and is shown as mean of quadruplicates + /- s.d. overlayed with data points of individual animals. (E, F, G) For clarity reasons, weight, clinical, and viral titers from young chACE2 mice (as shown in Fig 3) were included. Viral load in BAL (G) of young and aged chACE2 mice two days postinfection with wt and LAVNsp16 was determined by RT-qPCR and is shown as mean + /- s.d. overlayed with data points of individual animals. (A-G) Statistical analysis was performed by unpaired two-tailed t-tests. (H) ACE2 and GAPDH protein expression in lung tissue lysates of uninfected, young (8 weeks), or old (42 weeks) chACE2 and C57BL/6 (B6) mice is shown.