Extended Data Fig. 3: IdeS treatment allows for AAV8 vector readministration in NHPs.
Two male Cynomolgus monkeys with an anti-AAV8 NAb titer of 1:31.6 received an AAV8-hFIX vector (5 × 1012 vg kg−1) at day 0, with (NHP4, treated) or without (NHP1, control) an intravenous infusion of IdeS (500 µg kg−1) at day -1. At day 82 and 83, both NHPs received IdeS twice (500 µg kg−1 per infusion) followed by a second administration of the AAV8-hFIX vector (5 × 1012 vg kg−1) at day 84. b, Anti-AAV8 IgG measured over time in NHP4 after the first IdeS administration (n = 1 monkey per treatment group, triplicate independent measurements of each sample). The horizontal dotted line represents the levels of anti-AAV8 IgG in the control animal NHP1 (see Supplementary Table 1). c, hFIX in plasma and c, anti-AAV8 IgG at baseline and after the first vector administration (n = 1 monkey per treatment group, duplicate independent measurements of each sample). d, hFIX in plasma following AAV8-hFIX readministration (n = 1 monkey per treatment group, duplicate independent measurements of each sample). e, Western blot follow-up of total IgG cleavage between day 82 and 105 after the second IdeS treatment in NHP1 and NHP4. One representative out of two independent experiments shown. f, Anti-AAV8 IgG and g, NAbs measured over time in NHP1 and NHP4 after the second IdeS administration (n = 1 monkey per treatment group, duplicate independent measurements of each sample). All data are shown as mean ± s.d. Statistical analyses were performed by b, repeated measures one-way ANOVA with Dunnett’s multiple comparisons test (vs. Day -1); c,d, repeated measures two-way ANOVA with Sidak’s multiple comparisons test (vs. NHP1); f, repeated measures one-way ANOVA with Dunnett’s multiple comparisons test (vs. day -82), g, repeated measures, non-parametric one-way ANOVA with Dunn’s multiple comparisons test (vs. day -82).
