The vesicular stomatitis virus-based Ebola virus vaccine: From concept to clinical trials

Abstract

The devastating Ebola virus (EBOV) epidemic in West Africa in 2013-2016 accelerated the progress of several vaccines and antivirals through clinical trials, including the replication-competent vesicular stomatitis virus-based vaccine expressing the EBOV glycoprotein (VSV-EBOV). Extensive preclinical testing in animal models demonstrated the prophylactic and post-exposure efficacy of this vaccine, identified the mechanism of protection, and suggested it was safe for human use. Based on these data, VSV-EBOV was extensively tested in phase 1-3 clinical trials in North America, Europe and Africa. Although some side effects of vaccination were observed, these clinical trials showed that the VSV-EBOV was safe and immunogenic in humans. Moreover, the data supported the use of VSV-EBOV as an emergency vaccine in individuals at risk for Ebola virus disease. In this review, we summarize the results of the extensive preclinical and clinical testing of the VSV-EBOV vaccine.

Keywords: VSV-EBOV; animal models; clinical trials; filovirus; phase 1; phase 2; phase 3; preclinical testing.

Figure 1.

Preclinical testing of the VSV-EBOV vaccine in animal models. Recombinant VSV particles expressing the EBOV GP are produced from a cDNA clone of the VSV genome in which the VSV G is replaced with EBOV GP. The resulting vaccine has been tested in different animal models to assess protective prophylactic efficacy, time to immunity, post-exposure efficacy, cross-protection potential, as well as providing insight into the mechanism of protection.

Figure 2.

Concluded, ongoing and planned human clinical trials of VSV-EBOV. Since 2014, VSV-EBOV has been evaluated globally in phase 1, 2 and 3 clinical trials. The countries where these clinical trials were conducted, and their phase (1-3) are shown. Lines indicate completed clinical trials; arrows indicate clinical trials still ongoing at the time of this writing.