New England Journal of Medicine
January 26, 2017 Vol. 376 No. 4
A Recombinant Vesicular Stomatitis Virus Ebola Vaccine
Jason A. Regules, M.D., John H. Beigel, M.D., Kristopher M. Paolino, M.D., Jocelyn Voell, R.N., M.S., Amy R. Castellano, L.P.N., Zonghui Hu, Ph.D., Paula Muñoz, B.S., James E. Moon, M.D., Richard C. Ruck, M.D., Jason W. Bennett, M.D., Patrick S. Twomey, M.D., Ramiro L. Gutiérrez, M.D., Shon A. Remich, M.D., Holly R. Hack, M.S., Meagan L. Wisniewski, Ph.D., Matthew D. Josleyn, M.S., Steven A. Kwilas, Ph.D., Nicole Van Deusen, B.S., Olivier Tshiani Mbaya, M.D., Yan Zhou, Ph.D., Daphne A. Stanley, M.S., Wang Jing, M.S., Kirsten S. Smith, Ph.D., Meng Shi, M.A., Julie E. Ledgerwood, D.O., Barney S. Graham, M.D., Nancy J. Sullivan, Ph.D., Linda L. Jagodzinski, Ph.D., Sheila A. Peel, M.S.P.H., Ph.D., Judie B. Alimonti, Ph.D., Jay W. Hooper, Ph.D., Peter M. Silvera, Ph.D., Brian K. Martin, Ph.D., Thomas P. Monath, M.D., W. Jay Ramsey, M.D., Ph.D., Charles J. Link, M.D., H. Clifford Lane, M.D., Nelson L. Michael, M.D., Ph.D., Richard T. Davey, Jr., M.D., and Stephen J. Thomas, M.D., for the rVSVΔG-ZEBOV-GP Study Group*
N Engl J Med 2017; 376:330-341January 26, 2017DOI: 10.1056/NEJMoa1414216
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.
Full Text of Background…
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.
Full Text of Methods…
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.
Full Text of Results…
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.)