A Recombinant Vesicular Stomatitis Virus Ebola Vaccine

Abstract

Background The worst Ebola virus disease (EVD) outbreak in history has resulted in more than 28,000 cases and 11,000 deaths. We present the final results of two phase 1 trials of an attenuated, replication-competent, recombinant vesicular stomatitis virus (rVSV)–based vaccine candidate designed to prevent EVD. Methods We conducted two phase 1, placebo-controlled, double-blind, dose-escalation trials of an rVSV-based vaccine candidate expressing the glycoprotein of a Zaire strain of Ebola virus (ZEBOV). A total of 39 adults at each site (78 participants in all) were consecutively enrolled into groups of 13. At each site, volunteers received one of three doses of the rVSV-ZEBOV vaccine (3 million plaque-forming units [PFU], 20 million PFU, or 100 million PFU) or placebo. Volunteers at one of the sites received a second dose at day 28. Safety and immunogenicity were assessed. Results The most common adverse events were injection-site pain, fatigue, myalgia, and headache. Transient rVSV viremia was noted in all the vaccine recipients after dose 1. The rates of adverse events and viremia were lower after the second dose than after the first dose. By day 28, all the vaccine recipients had seroconversion as assessed by an enzyme-linked immunosorbent assay (ELISA) against the glycoprotein of the ZEBOV-Kikwit strain. At day 28, geometric mean titers of antibodies against ZEBOV glycoprotein were higher in the groups that received 20 million PFU or 100 million PFU than in the group that received 3 million PFU, as assessed by ELISA and by pseudovirion neutralization assay. A second dose at 28 days after dose 1 significantly increased antibody titers at day 56, but the effect was diminished at 6 months. Conclusions This Ebola vaccine candidate elicited anti-Ebola antibody responses. After vaccination, rVSV viremia occurred frequently but was transient. These results support further evaluation of the vaccine dose of 20 million PFU for preexposure prophylaxis and suggest that a second dose may boost antibody responses. (Funded by the National Institutes of Health and others; rVSVΔG-ZEBOV-GP ClinicalTrials.gov numbers, NCT02269423 and NCT02280408.)

Post-exposure treatments for Ebola and Marburg virus infections

“…Vaccines that were assessed in phase I and/or II studies during the 2013-2016 EBOV epidemic include rVSV-EBOV [268][269][270][271][272] , Ad5-EBOV [273][274][275] , rVSV-EBOV combined with rAd5-EBOV 276 , ChAd3-EBOV with or without MVA-EBOV [277][278][279][280] , Ad26-EBOV combined with MVA-EBOV 281 , and DNA encoding multiple filovirus GPs 282,283 . These EBOV vaccines generally elicited good immunogenicity against EBOV GP, and no serious adverse events were described.…”

Implementing an Ebola Vaccine Study — Sierra Leone

“…Early results on humoral and cell-mediated responses of ChAd3-EBOV were promising overall, although somewhat mixed (12,13), and similarly encouraging humoral responses to rVSV-ZEBOV were found at day 28 after vaccination (14). These small studies of both vaccines had not detected any safety issues, but in midDecember 2014, a phase I study under way in Switzerland that used rVSV-ZEBOV was paused to assess episodes of reported arthritis that began during the second week after vaccination.…”

“…In early January 2015, the study was resumed at a lower dose of vaccine (15). Investigators of other phase I studies in the United States examined their data but did not initially detect similar adverse events (14), although an association was detected later in some other trials also.…”

Glance at potential future combating of diseases: Bioengineered antimicrobial organisms

“…Currently trial success was exhibited with the VSV-ZEBOV recombinant, live attenuated, replicationcompetent genetically engineered vesicular stomatitis virus vaccine (Regules et al, 2015;Henao-Restrepo et Kashangura 55 al., 2017). The vaccine candidate (rVSV-ZEBOV) is genetically engineered to replace the VSV glycoprotein with the glycoprotein from a Zaire strain of Ebola virus (ZEBOV) (Regules et al, 2015).…”