Immunotherapeutic strategies to target vulnerabilities in the Ebolavirus glycoprotein

Summary The 2014 Ebola virus disease (EVD) outbreak in West Africa and the subsequent outbreaks of 2018–2020 in Equator and North Kivu provinces of the Democratic Republic of the Congo illustrate the public health challenges of emerging and reemerging viruses. EVD has a high case fatality rate with a rapidly progressing syndrome of fever, rash, vomiting, diarrhea, and bleeding diathesis. Recently, two monoclonal-antibody-based therapies received United States Food and Drug Administration (FDA) approval, and there are several other passive immunotherapies that hold promise as therapeutics against other species of Ebolavirus. Here, we review concepts needed to understand mechanisms of action, present an expanded schema to define additional sites of vulnerability on the viral glycoprotein, and review current antibody-based therapeutics. The concepts described are used to gain insights into the key characteristics that represent functional targets for immunotherapies against Zaire Ebolavirus and other emerging viruses within the Ebolavirus genus.