Intravenous (IV) administration of antiviral monoclonal antibodies (mAbs) can be challenging, particularly during an ongoing epidemic, due to the considerable resources required for performing infusions. An ebolavirus therapeutic administered via intramuscular (IM) injection would reduce the burdens associated with IV infusion and allow rapid treatment of exposed individuals during an outbreak. Here, we demonstrate how MBP134, a cocktail of two pan-ebolavirus mAbs, reverses the course of Sudan ebolavirus disease (Gulu variant) with a single IV or IM dose in non-human primates (NHPs) as late as five days post-exposure. We also investigate the utility of adding half-life extension mutations to the MBP134 mAbs, ultimately creating a half-life extended cocktail designated MBP431. When delivered as a post-exposure prophylactic or therapeutic, a single IM dose of MBP431 offered complete or significant protection in NHPs challenged with Zaire ebolavirus. In conjunction with previous studies, these results support the use of MBP431 as a rapidly deployable IM medical countermeasure against every known species of ebolavirus.

Marburg virus (MARV) causes a hemorrhagic fever disease in human and non-human primates with high levels of morbidity and mortality. Concerns about weaponization of aerosolized MARV have spurred the development of non-human primate (NHP) models of aerosol exposure. To address the potential threat of aerosol exposure, a monoclonal antibody that binds MARV glycoprotein was tested for its efficacy as a prophylactic. It was expressed with afucosylated N-glycans and two different sets of Fc amino acid mutations to increase serum half-life: MR186YTE and MR186LS. Each variant was tested in guinea pigs for preventing disease from an aerosolized MARV exposure. While both candidates provided significant protection (P<0.005), the observed efficacy conferred by MR186YTE was slightly superior and this version was selected for further testing in NHPs. MR186YTE was administered intramuscularly to NHPs at 15 or 5 mg/kg one month prior to MARV aerosol challenge. Seventy-five percent (3/4) of the 15 mg/kg dose group and fifty percent (2/4) of the 5 mg/kg dose group survived this lethal challenge. Serum analyses of showed that the NHP dosed with 15 mg/kg that succumbed to infection developed an anti-drug antibody response and therefore had no detectable MR186YTE at the time of challenge. Histopathological analyses found that NHPs that succumbed to disease had lesions consistent with previous reports of MARV disease and inflammatory lesions were noted in all lung lobes. In contrast, NHPs that survived aerosolized MARV exposure had background or non-active infiltrates. No evidence of MARV by immunohistochemistry was noted in the survivors. These results suggest that intramuscular dosing of mAbs may be a clinically useful prophylaxis for MARV aerosol exposure.