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 .).
RCT Entities:
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 .).
Authors: Julie E Ledgerwood; Adam D DeZure; Daphne A Stanley; Emily E Coates; Laura Novik; Mary E Enama; Nina M Berkowitz; Zonghui Hu; Gyan Joshi; Aurélie Ploquin; Sandra Sitar; Ingelise J Gordon; Sarah A Plummer; LaSonji A Holman; Cynthia S Hendel; Galina Yamshchikov; Francois Roman; Alfredo Nicosia; Stefano Colloca; Riccardo Cortese; Robert T Bailer; Richard M Schwartz; Mario Roederer; John R Mascola; Richard A Koup; Nancy J Sullivan; Barney S Graham Journal: N Engl J Med Date: 2014-11-26 Impact factor: 91.245
Authors: Lisa E Hensley; Sabue Mulangu; Clement Asiedu; Joshua Johnson; Anna N Honko; Daphne Stanley; Giulia Fabozzi; Stuart T Nichol; Thomas G Ksiazek; Pierre E Rollin; Victoria Wahl-Jensen; Michael Bailey; Peter B Jahrling; Mario Roederer; Richard A Koup; Nancy J Sullivan Journal: PLoS Pathog Date: 2010-05-20 Impact factor: 6.823
Authors: Thomas W Geisbert; Kathleen M Daddario-Dicaprio; Joan B Geisbert; Douglas S Reed; Friederike Feldmann; Allen Grolla; Ute Ströher; Elizabeth A Fritz; Lisa E Hensley; Steven M Jones; Heinz Feldmann Journal: Vaccine Date: 2008-10-18 Impact factor: 3.641
Authors: Ana Maria Henao-Restrepo; Ira M Longini; Matthias Egger; Natalie E Dean; W John Edmunds; Anton Camacho; Miles W Carroll; Moussa Doumbia; Bertrand Draguez; Sophie Duraffour; Godwin Enwere; Rebecca Grais; Stephan Gunther; Stefanie Hossmann; Mandy Kader Kondé; Souleymane Kone; Eeva Kuisma; Myron M Levine; Sema Mandal; Gunnstein Norheim; Ximena Riveros; Aboubacar Soumah; Sven Trelle; Andrea S Vicari; Conall H Watson; Sakoba Kéïta; Marie Paule Kieny; John-Arne Røttingen Journal: Lancet Date: 2015-08-03 Impact factor: 79.321
Authors: Katie Ewer; Tommy Rampling; Navin Venkatraman; Georgina Bowyer; Danny Wright; Teresa Lambe; Egeruan B Imoukhuede; Ruth Payne; Sarah Katharina Fehling; Thomas Strecker; Nadine Biedenkopf; Verena Krähling; Claire M Tully; Nick J Edwards; Emma M Bentley; Dhanraj Samuel; Geneviève Labbé; Jing Jin; Malick Gibani; Alice Minhinnick; Morven Wilkie; Ian Poulton; Natalie Lella; Rachel Roberts; Felicity Hartnell; Carly Bliss; Kailan Sierra-Davidson; Jonathan Powlson; Eleanor Berrie; Richard Tedder; Francois Roman; Iris De Ryck; Alfredo Nicosia; Nancy J Sullivan; Daphne A Stanley; Olivier T Mbaya; Julie E Ledgerwood; Richard M Schwartz; Loredana Siani; Stefano Colloca; Antonella Folgori; Stefania Di Marco; Riccardo Cortese; Edward Wright; Stephan Becker; Barney S Graham; Richard A Koup; Myron M Levine; Ariane Volkmann; Paul Chaplin; Andrew J Pollard; Simon J Draper; W Ripley Ballou; Alison Lawrie; Sarah C Gilbert; Adrian V S Hill Journal: N Engl J Med Date: 2015-01-28 Impact factor: 91.245
Authors: Chad E Mire; Andrew D Miller; Angela Carville; Susan V Westmoreland; Joan B Geisbert; Keith G Mansfield; Heinz Feldmann; Lisa E Hensley; Thomas W Geisbert Journal: PLoS Negl Trop Dis Date: 2012-03-20
Authors: Nancy J Sullivan; Thomas W Geisbert; Joan B Geisbert; Devon J Shedlock; Ling Xu; Laurie Lamoreaux; Jerome H H V Custers; Paul M Popernack; Zhi-Yong Yang; Maria G Pau; Mario Roederer; Richard A Koup; Jaap Goudsmit; Peter B Jahrling; Gary J Nabel Journal: PLoS Med Date: 2006-05-16 Impact factor: 11.069
Authors: Heinz Feldmann; Steven M Jones; Kathleen M Daddario-DiCaprio; Joan B Geisbert; Ute Ströher; Allen Grolla; Mike Bray; Elizabeth A Fritz; Lisa Fernando; Friederike Feldmann; Lisa E Hensley; Thomas W Geisbert Journal: PLoS Pathog Date: 2007-01 Impact factor: 6.823
Authors: Jeffrey R Kugelman; Mariano Sanchez-Lockhart; Kristian G Andersen; Stephen Gire; Daniel J Park; Rachel Sealfon; Aaron E Lin; Shirlee Wohl; Pardis C Sabeti; Jens H Kuhn; Gustavo F Palacios Journal: mBio Date: 2015-01-20 Impact factor: 7.867
Authors: Thomas W Geisbert; Kathleen M Daddario-Dicaprio; Mark G Lewis; Joan B Geisbert; Allen Grolla; Anders Leung; Jason Paragas; Lennox Matthias; Mark A Smith; Steven M Jones; Lisa E Hensley; Heinz Feldmann; Peter B Jahrling Journal: PLoS Pathog Date: 2008-11-28 Impact factor: 6.823
Authors: David K Clarke; R Michael Hendry; Vidisha Singh; John K Rose; Stephen J Seligman; Bettina Klug; Sonali Kochhar; Lisa Marie Mac; Baevin Carbery; Robert T Chen Journal: Vaccine Date: 2016-07-06 Impact factor: 3.641
Authors: May S ElSherif; Catherine Brown; Donna MacKinnon-Cameron; Li Li; Trina Racine; Judie Alimonti; Thomas L Rudge; Carol Sabourin; Peter Silvera; Jay W Hooper; Steven A Kwilas; Nicole Kilgore; Christopher Badorrek; W Jay Ramsey; D Gray Heppner; Tracy Kemp; Thomas P Monath; Teresa Nowak; Shelly A McNeil; Joanne M Langley; Scott A Halperin Journal: CMAJ Date: 2017-06-19 Impact factor: 8.262
Authors: Fatorma K Bolay; Greg Grandits; H Clifford Lane; Stephen B Kennedy; Melvin P Johnson; Mosoka P Fallah; Barthalomew Wilson; Wissedi S Njoh; Laura A McNay; Lisa E Hensley; Elizabeth S Higgs Journal: J Infect Dis Date: 2019-04-19 Impact factor: 5.226
Authors: Morrison O Jusu; Geoffrey Glauser; Jane F Seward; Mohamed Bawoh; Judith Tempel; Michael Friend; Daniel Littlefield; Michael Lahai; Hassan M Jalloh; Amara Bangali Sesay; Amanda F Caulker; Mohamed Samai; Vasavi Thomas; Nicholas Farrell; Marc-Alain Widdowson Journal: J Infect Dis Date: 2018-05-18 Impact factor: 5.226