Pan-filovirus monoclonal antibody cocktail protects against lethal challenge with Marburg virus in non-human primates.

Abstract

Abstract While disregarded in the past, the use of antibody therapeutics in the treatment of filovirus infection has been gaining traction in recent years. Early studies in our lab with the treatment of non-human primates (NHPs) with polyclonal antibodies from convalescent NHPs demonstrated protection against challenges with a lethal dose of Ebola virus (EBOV). Successes with monoclonal antibody (mAb) cocktails such as ZMapp™ have encouraged the development of a cocktail that may be protective against multiple species of filovirus. This may ultimately allow for the prepositioning of a single cocktail in filovirus prone locations, rather than storing and maintaining multiple cocktails at each location. We have previously described three antibodies, FVM04 and CA45, which can neutralize multiple species of ebolavirus, and MR191, which can neutralize marburgviruses, and have shown efficacy in rodent and NHP models of filovirus disease. In this study, we evaluated the efficacy of a pan-ebolavirus cocktail (FVM04+CA45) in combination with the Marburg virus specific mAb MR191 in a pan-filovirus cocktail (FVM04+CA45+MR191), in the NHP model of Marburg virus disease. Both the pan-ebolavirus and pan-filovirus cocktails have been shown to be efficacious against lethal challenge with Sudan virus (SUDV) or EBOV in the rhesus macaque model. These data are the first to demonstrate protective efficacy of MR191 as part of a pan-filovirus cocktail against MARV in the NHP model of disease.