Figure 3.

Single-dose intranasal VHH-IgA1.1 protects K18-ACE2 transgenic mice from SARS-CoV-2 infection. (A) Schematic of VHH-IgA1.1 intranasal delivery and SARS-CoV-2 infection. (B, C) Weight loss (B) and survival (C) of K18-ACE2 transgenic mice infected intranasally with SARS-CoV-2 (2.5x10⁴ PFU/mouse) with a 1 h intranasal pre-treatment of 10mg/kg IRR-IgA isotype control (n=5), VHH-monomer (n=5) or VHH-IgA1.1 (D-F) QPCR analysis of SARS-CoV-2-N (D), Nsp14 (E) ORF1 (F) in lung tissue of K18-ACE2 transgenic mice infected with SARS-CoV-2 for 48 h with a 1 h intranasal pre-treatment of 10mg/kg IRR-IgA1 isotype control (n=5) or VHH-IgA1.1 (n=5). (G–J) Weight loss and survival of K18-ACE2 transgenic mice infected intranasally with SARS-CoV-2 (2.5x10⁴ PFU/mouse) and treated with 10mg/kg IRR-IgA1 isotype control (n=5) or VHH-IgA1.1 (n=5) 6 h (G, H) or 12 h (I, J) after infection. (K, M) Weight loss of K18-ACE2 transgenic mice infected intranasally with Alpha (K) and Omicron (N) (1x10⁵ PFU/mouse) variant of SARS-CoV-2 followed by pre-treatment of 10mg/kg IRR-IgA1 isotype control (n=5) or VHH-IgA1.1 (n=5). (L, N) QPCR analysis of SARS-CoV-2-N in lung tissue of K18-ACE2 transgenic mice infected with SARS-CoV-2 Alpha (L) and Omicron (N) for 48 h with a 1 h intranasal pre-treatment of 10mg/kg 10mg/kg IRR-IgA1 isotype control (n=5) or VHH-IgA1.1 (n=5). **p<0.001 ***p<0.0001, ****p<0.00001. (C, H, J Mantel–Cox survival analysis). Error bars show means ± SEM.