Fig. 2 | Nature Communications

Fig. 2

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

Fig. 2

SVP[Rapa] treatment enables AAV8 re-administration in nonhuman primates. a Protocol outline. Male naive cynomolgus monkeys were treated i.v. with 2 × 1012 vg kg−1 of AAV8-Gaa vector and either SVP[Rapa] (3 mg kg−1, n = 2, SVP[Rapa]#1 and SVP[Rapa]#2) or SVP[empty] control (n = 1) and then challenged i.v. on day 30 with 2 × 1012 vg kg1 of AAV8-hF.IX vector and either SVP[Rapa] or SVP[empty] control, as described above. b, c Analysis of b anti-AAV8 IgG antibodies and c anti-AAV8 IgM antibody responses measured by ELISA. d Analysis of anti-AAV8 neutralizing antibodies (NAb) measured with a cell-based neutralization assay. e Analysis of anti-AAV8 IgG secreting B cells in splenocytes measured by B ELISpot. Data are shown as individual replicates and the bars represent mean ± s.d. The dotted line indicates the threshold for positivity corresponding to 50 spot forming units (SFU) per million cells. f Plasma hF.IX antigen levels quantified by ELISA at the indicated time points following administration of AAV8-hF.IX vector. g AAV8-hF.IX vector genome copy number (VGCN) per diploid genome in liver. The symbols represent individual liver lobes (left, right, caudate and quadrate) and the bars represent the mean ± s.d. (4 liver lobes per monkey; one-way ANOVA with Tukey post hoc test, **p < 0.01, ****p < 0.0001) The arrows represent the timing of each AAV8 vector infusion

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