Protective efficacy of AAV-expressed bNAbs co-delivered with PD-L1

However, host immune responses, specifically anti-drug antibodies (ADA), limit sustained bNAb expression11-17. Here, we tested whether PD-L1-mediated immune shielding could improve the consistency of AAV-delivered bNAb expression from muscle tissue in rhesus macaques.

We show that AAV9.PD-L1 co-delivery with AAV9.10-1074 or AAV9.3BNC117 reduced the occurrence of ADA responses and improved the durability of bNAb expression for one year post administration. Macaques with sustained serum bNAb concentrations were protected against ten repeated SHIVAD8-EO challenges. In macaques that received AAV9.PD-L1 vectors, we observed reduced inflammation in muscle tissue harvested over one year post-AAV administration.