Figure 2. Prevention and clearance of chronic HCV infection using a CLDN1-specific mAb in vivo.

(a, b) Prevention studies. Chimeric uPA-SCID mice received 500 μg CLDN1-specific (n=5) or control mAb (n=4) on days −1, 1 and 5 (arrows) of inoculation (star) with genotype 1b (a) or genotype 4 (b) HCV-containing serum. One infected mouse injected with control mAb died on day 26 (a, cross). (c-e) Treatment studies. Chimeric uPA-SCID mice were chronically infected with HCVcc Jc1¹⁵ (genotype 2a/2a) (c), HCVcc VL-JFH1¹⁷ (genotype 1b/2a) (d) or serum of genotype 2a (e). Twenty-four to 50 days following inoculation, the animals received 500 μg control (c, d, e; n=4, 3 and 4 respectively) or CLDN1-specific mAb (c, d, e; n=5, 5 and 6 respectively) each week (arrows) for 4 weeks. Two CLDN1-specific mAb treated mice were sacrificed following viral clearance for FISH studies (e). (f-j) Serum concentration of CLDN1-specific mAb from (a-e respectively) was determined by ELISA. Serum viral load (a-e) was quantified by the clinically licensed Abbott RealTime™ HCV assay. The horizontal dashed line indicates the limit of quantification (LOQ). (c, d, h, i) The viral load and antibody concentration of the mice exhibiting a relapse is indicated by a dashed line. Values of individual animals are shown.