Review Article Ebola virus vaccines: Where do we stand? Vincent Pavot The Jenner Institute, University of Oxford, Oxford, UK abstract article info Article history: Received 24 October 2016 accepted with revision 26 October 2016 Available online 28 October 2016 The recent outbreak of Ebola virus disease in West Africa has led to more than 11,000 deaths, with a peak in mor- tality from August through December of 2014. A meeting convened by the World Health Organization (WHO) in September 2014, concluded that an urgent unmet need exists for efficacy and safety testing of the Ebola virus vac- cine candidates and that clinical trials should be expedited. These vaccines could be used both in an outbreak set- ting and to provide long-term protection in populations at risk of sporadic outbreaks. A number of vaccines have been evaluated in phase 1 trials, but the two most advanced first-generation Ebola vaccine candidates are the live replicating vesicular stomatitis virus (rVSV) and the replication-defective chim- panzee adenovirus 3 (ChAd3). This review focuses on these two vaccines in clinical development and discusses the future opportunities and challenges faced in the licensure and deployment of Ebola virus vaccines. Crown Copyright © 2016 Published by Elsevier Inc. All rights reserved. Keywords: Clinical trials Ebola virus Immunology Vaccines Viral vectors Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 2. rVSV-ZEBOV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 3. ChAd3-ZEBOV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 4. Prime-boost strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 4.1. ChAd3-ZEBOV/MVA-BN-Filo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 4.2. Ad26-ZEBOV/MVA-BN-Filo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 5. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 Declaration of conflicting interests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 1. Introduction Ebola virus disease (EVD) is a severe, often fatal, zoonotic filovirus infection. Since its discovery in central Africa in 1976, five species of Ebolavirus (EBOV) have been isolated: Zaire ebolavirus (ZEBOV), Sudan ebolavirus (SEBOV), Taï Forest ebolavirus, Bundibugyo ebolavirus (BEBOV) and Reston ebolavirus [1]. ZEBOV is responsible for the recent outbreak in West Africa (2013–2016), the largest outbreak ever record- ed since the virus was discovered in 1976, with a total number of 28,616 confirmed, probable, or suspected cases in Guinea, Liberia, and Sierra Leone, including 11,310 reported deaths (as of April 13, 2016) [2]. The WHO declared the end of Ebola transmission in Guinea on 29 December 2015, in Liberia on 14 January 2016, and in Sierra Leone on 17 March 2016. However, the development of a durable and effective Ebola vaccine is a priority, both to eliminate the remnants of the out- break and to prevent and control future epidemics. The first wave of Ebola vaccine development, beginning soon after the discovery of the virus, focused on attempts to inactivate the virus. Since then, preclinical development of a variety of different platforms including DNA vaccines, recombinant viral vectors, recombinant pro- teins, subunit proteins and virus-like particles (VLPs) have been progressed. In most cases, a replicating viral infection is very effective at eliciting robust immune responses in a host that may last for several years. This is in contrast to many recombinant antigens that are delivered either as subunit DNA plasmids or proteins; although these are considered to be reasonably safe (dependent on the adjuvant), they have frequently suf- fered from poor immunogenicity. Conversely, viral vaccine vectors that Clinical Immunology 173 (2016) 44–49 http://dx.doi.org/10.1016/j.clim.2016.10.016 1521-6616/Crown Copyright © 2016 Published by Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Clinical Immunology journal homepage: www.elsevier.com/locate/yclim