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N Engl J Med. 2017 Jan 26;376(4):330-341. doi: 10.1056/NEJMoa1414216. Epub 2015 Apr 1.

A Recombinant Vesicular Stomatitis Virus Ebola Vaccine.

Author information

1
From the Walter Reed Army Institute of Research (J.A.R., K.M.P., A.R.C., J.E.M., R.C.R., J.W.B., P.S.T., S.A.R., H.R.H., M.S., L.L.J., S.A.P., N.L.M., S.J.T.) and Naval Medical Research Center (R.L.G.), Silver Spring, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research (J.H.B., W.J.), and the U.S. Army Medical Research Institute of Infectious Diseases (M.L.W., M.D.J., S.A.K., N.V.D., K.S.S., J.W.H., P.M.S.), Frederick, and the National Institute of Allergy and Infectious Diseases (NIAID) (J.V., Z.H., P.M., H.C.L., R.T.D.) and NIAID Vaccine Research Center (O.T.M., Y.Z., D.A.S., J.E.L., B.S.G., N.J.S.), Bethesda - all in Maryland; the Public Health Agency of Canada, Ottawa (J.B.A.); and BioProtection Systems-NewLink Genetics, Ames, IA (B.K.M., T.P.M., W.J.R., C.J.L.).

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; rVSV∆G-ZEBOV-GP ClinicalTrials.gov numbers, NCT02269423 and NCT02280408 .).

PMID:
25830322
PMCID:
PMC5408576
DOI:
10.1056/NEJMoa1414216
[Indexed for MEDLINE]
Free PMC Article

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