Next Steps for Ebola Vaccination: Deployment in Non-Epidemic, High-Risk Settings.

Abstract

The catastrophic West Africa Ebola epidemic that resulted in approximately 28,200 cases and 11,300 deaths over 22 months has been reduced to intermittent and, thus far, rapidly controlled flare ups in Liberia, Guinea, and Sierra Leone. During the period of most widespread and intense transmission, extraordinary efforts to develop, produce, and field-test an Ebola vaccine in the outbreak setting generated promising results. The combined findings of four parallel Phase I studies on healthy adults in Gabon, Kenya, Germany, and Geneva demonstrated safety and immunogenicity of the recombinant vesicular stomatitis virus (rVSV)-vectored Zaire ebolavirus (rVSV-ZEBOV) vaccine [1]. Glycoprotein-binding antibodies were detected for all vaccinated participants irrespective of dose and, although arthralgia, fever, and maculopapular rash were correlated with immunization, the mild symptoms were transient and easily treated; the vaccine was deemed safe with a high likelihood of acceptance [1]. More recently, it has been suggested that the rVSV vaccine effectively protects against Ebola virus disease (EVD) infections among the contacts of symptomatic cases in intense transmission settings [2,3]. Other candidates include the chimpanzee adenovirus type 3 Ebola vaccine (cAd3-EBO), which has been demonstrated as immunogenic and safe in humans [4]. Additionally, sustained protection against lethal Zaire ebolavirus (EBOV) challenge in macaques was achieved using ChAd3, given a modified vaccinia Ankara (MVA) boost after two months [5]. Largely mediated by CD8+ cells, a protective effect against EBOV has likewise been established in macaques for a vaccine based on recombinant adenovirus virus serotype 5 (rAd5) encoding Ebola virus glycoprotein (GP) [6–8]. Across all vaccine candidates [9], large-scale trials in human populations are unlikely to yield sufficient statistical power for determining efficacy and duration of protective immunity given the fortunate downturn in transmission events. However, if an Ebola vaccine is approved for post-marketing surveillance without additional Phase III efficacy studies, there is an opportunity to prepare vaccine infrastructure, including stockpiling and administration systems, in non-emergency but high-risk settings.