Adeno-associated virus 6.2FF (AAV6.2FF)–mediated expression of monoclonal antibodies provides complete protection against mouse-adapted Ebola virus (MA-EBOV) challenge. C57BL/6 mice (n = 6 per group) received an intramuscular injection of 2 × 1011 vector genomes of single AAV6.2FF-mAbs or a cocktail of 2 × 1011 vector genomes of AAV6.2FF-2G4 and 2 × 1011 vector genomes of AAV6.2FF-5D2 for a total dose of 4 × 1011 vg. All AAV monotherapies were given 14 days prior to intraperitoneal challenge with 1000 times the lethal dose (50%) of MA-EBOV. A and B, Kaplan-Meyer survival plots of AAV6.2FF-2G4, AAV6.2FF-5D2, and AAV6.2FF-7C9 monotherapies (A) and averaged mouse group weights (B). Survival of treated groups was compared to that of the mock group by using the Mantel-Cox log rank test. P = .0009 for 2G4 and P = .0005 for 5D2 and 7C9. C and D, Kaplan-Meyer survival plots of AAV6.2FF-2G4/AAV6.2FF-5D2 cocktail survival plots at various lead times between AAV administration and MA-EBOV challenge (C) and averaged mouse group weights (D). Survival of treated groups was compared to the mock group using the Mantel-Cox log rank test. P = .005 for 14 and 7 days, P = .2801 for 3 days, and P>0.9999 for 1 day and 0 days.