Does the presence of binding antibodies versus neutralizing antibodies affect AAV vector transduction efficiency in hepatocytes and mice?
Neutralizing and binding antibodies have opposite effects on AAV vector transduction, with binding antibodies enhancing internalization and transgene expression.
, imaging of hepatocytes exposed to AAV vectors pre-incubated with either NAbs or BAbs revealed that virus is taken up by cells in both cases. Whereas no successful transduction was observed when AAV was pre-incubated with NAbs, an increased capsid internalization and transgene expression was observed in the presence of BAbs. Accordingly, AAV8 vectors administered to mice passively immunized with anti-AAV8 BAbs showed a more efficient liver transduction and a unique vector biodistribution profile compared to mice immunized with NAbs. These results highlight a virtually opposite effect of neutralizing and binding antibodies on AAV vectors transduction.
Fitzpatrick et al. (Tue,) studied this question.
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