Fig. 1 | Nature Communications

Fig. 1

From: Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration

Fig. 1

SVP[Rapa] treatment prevents anti-AAV capsid antibody responses in mice. a Protocol outline. Male C57BL/6 mice (n = 5 per group) were treated intravenously with 4 × 1012 vg kg−1 of AAV8-luc together with SVP[Rapa] (200 µg) or with SVP[empty] control. Three weeks later, animals were challenged with 4 × 1012 vg kg1 of AAV8-hF.IX vector mixed with either SVP[Rapa] (200 µg) or SVP[empty] control. One additional control group (n = 5) of naive animals received 4 × 1012 vg kg−1 of AAV8-hF.IX vector alone at day 21 (defined as “AAV8-hF.IX only”). b Analysis of anti-AAV8 IgG antibodies measured by ELISA (**p < 0.01, ****p < 0.0001, refers to the significance between SVP[Rapa] and SVP[empty] or AAV8-hF.IX groups). c Anti-AAV8 neutralizing antibodies (NAbs) titers on day 54. d hF.IX antigen levels in plasma on day 54 determined by ELISA. e AAV8 vector genome copy number (VGCN) per diploid genome performed after killing (day 53). f Protocol outline. Three groups of C57BL/6 male mice (n = 5 per group) were prime-boosted (days 0 and 93, arrows) with 5 × 1011 vg kg−1 of AAV8-SEAP alone, or AAV8-SEAP mixed with SVP[Rapa] (50 µg), or AAV8-SEAP mixed with SVP[Empty] control. g Anti-AAV8 IgG antibodies measured by ELISA (*p < 0.05, **p < 0.01, refers to significance between SVP[Rapa] and AAV-SEAP). h Expressed SEAP activity in serum. Data are shown as mean ± s.d. Statistical analyses were performed by two-way ANOVA with Tukey post hoc test in b, g, and h, and by unpaired, two-tail t-test in c and by one-way ANOVA with Tukey post hoc test in d and e (*p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001; ns not significant)

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