JAMA
http://jama.jamanetwork.com/issue.aspx

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Online First
March 05, 2015
Editorial
Emergency Treatment for Exposure to Ebola Virus: The Need to Fast-Track Promising Vaccines
Thomas W. Geisbert, PhD.
JAMA. Published online March 05, 2015. doi:10.1001/jama.2015.2057

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 Africa with more than 23 000 cases and 9000 deaths2 also demonstrates 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 been made 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 first-generation recombinant vesicular stomatitis virus–based Ebola vaccine (VSVΔG-ZEBOV)5 to treat a physician who experienced a needlestick in an Ebola treatment unit in Sierra Leone during the current Ebola virus outbreak. A single dose of the VSVΔG-ZEBOV vaccine was administered approximately 43 hours after the potential exposure. The patient experienced a transient febrile syndrome after vaccination. Importantly, no evidence of Ebola virus infection was detected, and the vaccine elicited strong innate and Ebola virus–specific adaptive immune responses. Most significantly, the vaccine, which expresses the surface glycoprotein of Ebola virus, was able to induce an IgG antibody response against the Ebola virus glycoprotein at a level that has been associated with protection of nonhuman primates.5
It is difficult to draw any definitive conclusions from a single case report. The inability to detect evidence of Ebola virus infection most likely is because there was not an actual 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 vaccination was less notable in the German case compared with the patient in the case report by Lai et al…4

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Preliminary Communication
Emergency Postexposure Vaccination With Vesicular Stomatitis Virus–Vectored Ebola Vaccine After Needlestick
Lilin Lai, MD, Richard Davey, MD, Allison Beck, MPAS, et al.
JAMA. Published online March 05, 2015. doi:10.1001/jama.2015.1995
Abstract
Importance
Safe and effective vaccines and drugs are needed for the prevention and treatment of Ebola virus disease, including following a potentially high-risk exposure such as a needlestick.
Objective
To assess response to postexposure vaccination in a health care worker who was exposed to the Ebola virus.
Design and Setting
Case report of a physician who experienced a needlestick while working in an Ebola treatment unit in Sierra Leone on September 26, 2014. Medical evacuation to the United States was rapidly initiated. Given the concern about potentially lethal Ebola virus disease, the patient was offered, and provided his consent for, postexposure vaccination with an experimental vaccine available through an emergency Investigational New Drug application. He was vaccinated on September 28, 2014.
Interventions
The vaccine used was VSVΔG-ZEBOV, a replicating, attenuated, recombinant vesicular stomatitis virus (serotype Indiana) whose surface glycoprotein gene was replaced by the Zaire Ebola virus glycoprotein gene. This vaccine has entered a clinical trial for the prevention of Ebola in West Africa.
Results
The vaccine was administered 43 hours after the needlestick occurred. Fever and moderate to severe symptoms developed 12 hours after vaccination and diminished over 3 to 4 days. The real-time reverse transcription polymerase chain reaction results were transiently positive for vesicular stomatitis virus nucleoprotein gene and Ebola virus glycoprotein gene (both included in the vaccine) but consistently negative for Ebola virus nucleoprotein gene (not in the vaccine). Early postvaccination cytokine secretion and T lymphocyte and plasmablast activation were detected. Subsequently, Ebola virus glycoprotein-specific antibodies and T cells became detectable, but antibodies against Ebola viral matrix protein 40 (not in the vaccine) were not detected.
Conclusions and Relevance
It is unknown if VSVΔG-ZEBOV is safe or effective for postexposure vaccination in humans who have experienced a high-risk occupational exposure to the Ebola virus, such as a needlestick. In this patient, postexposure vaccination with VSVΔG-ZEBOV induced a self-limited febrile syndrome that was associated with transient detection of the recombinant vesicular stomatitis vaccine virus in blood. Strong innate and Ebola-specific adaptive immune responses were detected after vaccination. The clinical syndrome and laboratory evidence were consistent with vaccination response, and no evidence of Ebola virus infection was detected.