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. 2021 Jun 16;32(11-12):563–580. doi: 10.1089/hum.2020.269

Figure 2.

Figure 2.

Assessment of total and neutralizing anti-AAVrh.10 antibody titers in NHP CSF for humoral responses evoked by administration of AAVrh.10hARSA. Total anti-AAVrh.10 antibody and neutralizing anti-AAVrh.10 antibody titers in the CSF were determined after intraparenchymal administration of AAVrh.10hARSA (low dose 2.85 × 1010 gc, 2.4 × 109 gc/site or high dose 1.5 × 1012 gc, 1.3 × 1011 gc/site), AAVrh.10Null, or PBS at two time points, before vector administration (day 0) and before necropsy (at 1, 13, 26, or 52 weeks). At indicated time, the NHPs were sedated for sampling of CSF using cisterna magna with assessment of antibody titers in CSF. The total antibody titers are expressed as the reciprocal of the serum dilution. The neutralizing antibody titers are expressed as the reciprocal of serum dilution at which 50% inhibition of AAVrh.10Luc was observed. Shown are the results for each NHP in the study, color-coded by treatment (yellow, PBS; red, AAVrh.10Null; blue, AAVrh.10hARSA-high dose; brown, AAVrh.10hARSA-low dose). (A, B) Total CSF antibody titers. (C, D) Neutralizing antibody titers. (A, C) Females (n = 13); (B, D) Males (n = 11). The day 0 and necropsy CSF values are connected for individual NHP. Assay LOD was 100; any sample results below the LOD were recorded as 1 by convention. Background of the assay was 2.0, as represented by the dashed line. (E, F) Comparison of CSF total to serum total anti-AAVrh.10 antibody titers evoked by administration of AAVrh.10hARSA. The data in Figures 1A, B and (A, B) were compared as CSF total anti-AAVrh.10 antibody titers versus serum total anti-AAVrh.10 antibody titers for each corresponding each time point. (E) Female (Fig. 1A vs. A); (F) Males (Fig. 1B vs. B). (G, H) Comparison of CSF neutralizing anti-AAVrh.10 titers to serum anti-AAVrh.10 neutralizing titers. The data in Figures 1C, D and (C, D) were compared as CSF neutralizing anti-AAVrh.10 antibody titers versus serum neutralizing anti-AAVrh.10 antibody titers for each corresponding each time point. (G) Female (1C vs. C); (H) Males (1D vs. D). CSF, cerebrospinal fluid.