In vivo delivery of engineered synthetic DNA-encoded SARS-CoV-2 monoclonal antibodies for pre-exposure prophylaxis in non-human primates

Figures

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  Figure 1.. Human IgG antibody pharmacokinetic expression levels in the serum of cynomolgus macaques following administration of the DMAb-2130-YTE and DMAb-2196-YTE cocktail in cynomolgus macaques. (a) Overview of study. (b) Expression levels in Group 1 (n = 4), receiving two DMAb administrations. (c) Expression levels in Group 1 NHP M16912. (d) Expression levels in Group 2 (n = 5), receiving a single DMAb administration. (e) Detection of 2196 Fab by RBD K444A ELISA. (f) Detection of 2130 Fab by RBD F486A ELISA. (g) Detection of 2196 and 2130 Fab by RBD K444A and in NHP M16912.

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  Figure 2.. SARS-CoV-2 authentic virus and pseudovirus titers in the serum of cynomolgus macaques following administration of DMAb-2130-YTE and DMAb-2196-YTE. Neutralization assays were performed on sera samples collected on day 15 post-DMAb administration. (a) Neutralization ID50 titers against authentic SARS-CoV-2 USA-WA1/2020 (WT lineage) and hCoV-19/USA/PHC658/2021 (Delta lineage). Graphs display animals all together (i, ii) and by individual group (iii, iv). (b) SARS-CoV-2 pseudovirus neutralization titers against WT, Beta, and Delta lineage pseudoviruses. Graphs display animals all together (i-iii) and by group (iv-vi). IC50 neutralization titers for (c) Live virus and (d) Pseudovirus. Omicron BA.2 and BA2.12 pseudovirus (e) ID50 titersand (f) IC50 values. Individual animals are displayed on the graphs, along with the geometric mean titer and geometric standard deviation. (*) p < 0.05 and (**) p < 0.01.

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  Figure 3.. Overview of serum expression and neutralizing activity of DMAbs in rhesus macaques. (a) Schematic overview of DMAb delivery in rhesus macaques. (b) Human IgG antibody expression levels in the serum with no DMAb, DMAb-YTE, or DMAb-WT cocktails. (c) Neutralization ID50 titers against authentic SARS-CoV-2 USA-WA1/2020 (WT lineage). (d) Pseudovirus neutralization ID50 titers against WT lineage. Group 1 (control) is depicted in grey circles, Group 2 (DMAb-YTE) is depicted in orange triangles, Group 3 (DMAb-WT) is depicted in purple squares. Lines represent the mean and error bars represent the standard deviation.

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  Figure 4.. Clinical scores, viral loads, and histopathological analysis. (a) Clinical scores in control and DMAb-administered rhesus macaques following SARS-CoV-2 challenge. (b) Viral loads in nasal washes and bronchioalveolar lavage (BAL) following SARS-CoV-2 challenge detected by subgenomic qPCR. (b) (i) Nasal swab viral loads from individual animals are shown. (ii) Nasal swabs on day 5 post-challenge. (c) (i) BAL washes from individual animals are shown. (ii) BAL on day 3 post-challenge. Bars represent the mean and standard deviation. p < 0.05 is considered significant. LOD = assay limit of detection. (d) Photomicrographs of histological sections of the lung (top row HE, 100x) and anti-SARS-CoV-2 IHC (middle row 100x; bottom row 400x). Lesions are minimal to mild and demonstrate increased alveolar septal thickening and septal and alveolar inflammation. Immunoreactivity is scattered and sparse when present and appears specific to type I and type II pneumocytes.