Emergency Treatment for Exposure to Ebola Virus: The Need to Fast-track Promising Vaccines

Ebola virus is among the most deadly pathogens, with case fatality rates of up to 90%.1 Ebola virus is categorized as a tier 1 pathogen by the US government because of its potential for deliberate misuse with significant potential for mass casualties. The current outbreak of Ebola virus in West Africawithmore than23 000casesand9000deaths2alsodemonstrates the long-underestimated public health threat that Ebola virus poses as a natural human pathogen. There are no licensed vaccines or postexposure treatments for combating Ebola virus. However, substantial progress has beenmade in developing vaccines and antivirals that can protect laboratory animals against lethal disease.1,3 Advancing these interventions for human use is a matter of utmost urgency. In this issue of JAMA, Lai et al4 report the use of a firstgeneration recombinantvesicular stomatitisvirus–basedEbola vaccine (VSVΔG-ZEBOV)5 to treat aphysicianwhoexperienced aneedlestick in anEbola treatment unit in Sierra Leoneduring the current Ebola virus outbreak. A single dose of the VSVΔGZEBOVvaccinewasadministeredapproximately43hoursafter thepotential exposure. Thepatient experienceda transient febrile syndrome after vaccination. Importantly, no evidence of Ebolavirusinfectionwasdetected,andthevaccineelicitedstrong innateandEbolavirus–specificadaptiveimmuneresponses.Most significantly, thevaccine,whichexpresses thesurfaceglycoproteinofEbolavirus,wasable to inducean IgGantibodyresponse against theEbola virus glycoprotein at a level that has been associatedwith protection of nonhuman primates.5 It is difficult to draw any definitive conclusions from a single case report. The inability todetect evidenceofEbola virus infectionmost likely is because therewasnot anactual exposure; however, it cannot be completely ruled out that the intervention was effective in controlling Ebola virus replication. Even though this patient experienced some adverse events after vaccination, the patient reported having traveler’s diarrhea prior to receiving the VSVΔG-ZEBOV vaccine; therefore, it is also not possible to draw any strong conclusions regarding any adverse events from this case in regard to the safety of the vaccine. This is the second time that the VSVΔG-ZEBOV vaccine has been used to treat a potential exposure to Ebola virus. The initial use occurred in 2009 for a laboratory worker in Germany6 and also involved a needlestick injury. The results of that incident were nearly identical; however, the severity of adverse events following vaccinationwas lessnotable in theGermancase comparedwith the patient in the case report by Lai et al.4 The2 incidents involving theuseof theVSVΔG-ZEBOVvaccine for the treatment of high-risk Ebola virus exposures further reinforce the need for public health approaches that prevent and control outbreaks. Efforts to develop effective vaccines and treatments against Ebola virus began soon after its discovery in 1976. However, advances were slow until the decadeof the 2000swhenat least 10different preventive vaccines were developed that conferred complete protection in the criterion standardnonhumanprimatemodels.1 Postexposure treatments and therapies that canprotect nonhumanprimates against Ebola virus have been much more difficult to develop. Similar to the rabies vaccine, the VSVΔG-ZEBOV vaccine can be used both as a conventional preventive vaccine and as a postexposure treatment. When used as a treatment, the VSVΔG-ZEBOV vaccine protected 50% of nonhuman primates against lethal Ebolavirus (Zaire species) infectionwhen given shortly after exposure.7 Only 2 potential therapies, ZMapp8 and TKM-Ebola,9 have been shown to completely protect 100% of nonhuman primates from a lethal Ebola virus (Zaire species) infection when administered after exposure. Both drugs have been administered under compassionate use during the current outbreak to treat a number of patients repatriated to Europe and the United States. Even though these patients have had very high survival rates, the role of ZMapp and TKM-Ebola in the outcome is unknown because in many cases they received multiple types of experimental therapies, including convalescent serum, and also likely benefited from the advanced supportive medical care in specialized facilities. Other treatments such as brincidofovir and favipiravir also have been used to treat patients infected with Ebola virus during the current outbreak; however, their benefit is even more difficult to measure because neither treatment has been associated with strong protection of nonhuman primates against Ebola virus. An important point noted in the report by Lai et al4 is that the patient declined other experimental drugs in lieu of the VSVΔG-ZEBOV vaccine. This also raises issues regarding patient consent and theuseof experimental therapies. This is an important consideration because ultimately the patient or a representative of the patient makes the decision and should be informed of all options, available data, and risks. It is unknownwhat other drugswere offered to the patient in the report byLai et al.4 Shortagesof ZMappduring the currentEbola virus outbreak have been reported, and it is clear that even though promising antivirals have been developed, they have Related article page 1249 Opinion