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N Engl J Med. 2016 Apr 28;374(17):1647-60. doi: 10.1056/NEJMoa1502924. Epub 2015 Apr 1.

Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe.

Author information

1
From the Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon (S.T.A., J.F.F., A.A.A., E.B.B., J.S.B., M.P.G., A.L.K., B. Lell, M.M.-L., B.M., M.R., S.K., P.G.K.); Institut für Tropenmedizin, Universitätsklinikum Tübingen, and German Center for Infection Research, Tübingen (S.T.A., J.F.F., A.A.A., E.B.B., J.S.B., M.P.G., A.L.K., B. Lell, M.M.-L., B.M., M.R., S.K., P.G.K.), University Medical Center Hamburg-Eppendorf, 1st Department of Medicine (M.E.Z., C.D., R.K., A.W.L., A.N., S.S., H.C.S., M.M.A.), and Institute for Clinical Chemistry and Laboratory Medicine (F.R.S.), German Center for Infection Research, partner site Standort Hamburg-Lübeck-Borstel (C.D., A.N., J.S.-C., H.C.S., M.M.A.), Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology (M.A.), Clinical Trial Center North (S. Borregaard, A.J.), and Bernhard Nocht Institute for Tropical Medicine, World Health Organization (WHO) Collaborating Center for Arbovirus and Hemorrhagic Fever Reference and Research, National Reference Center for Tropical Infectious Diseases (J.S.-C.), Hamburg, Philipps University Marburg, Institute for Virology, and the German Center for Infection Research (DZIF), partner site Giessen-Marburg-Langen, Marburg (V.K., N.B., M.E., S.K.F., T.S., S. Becker), and the Division of Veterinary Medicine, Paul Ehrlich Institute, Langen (R.K.) - all in Germany; the Infection Control Program (A.H.), Divisions of Infectious Diseases (A.H., J.-A.D., L.K.), Clinical Epidemiology (C.C.), Rheumatology (A.F.), and Dermatology (G.K.), and Centers for Clinical Research (J.D., A.M.) and Vaccinology (C.-A.S.), Geneva University Hospitals and Faculty of Medicine, the Virology Laboratory, Geneva University Hospitals (S.Y., A.R.G., L.K.), WHO Collaborative Center for Vaccinology, Faculty of Medicine (F.A., B. Lemaître, C.-A.S.), and the WHO (P.F., V.M., M.-P.K.) - all in Geneva; the Kenya Medical Research Institute-Wellcome Trust Research Program, Center for Geographic Medicine

Abstract

BACKGROUND:

The replication-competent recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing a Zaire ebolavirus (ZEBOV) glycoprotein was selected for rapid safety and immunogenicity testing before its use in West Africa.

METHODS:

We performed three open-label, dose-escalation phase 1 trials and one randomized, double-blind, controlled phase 1 trial to assess the safety, side-effect profile, and immunogenicity of rVSV-ZEBOV at various doses in 158 healthy adults in Europe and Africa. All participants were injected with doses of vaccine ranging from 300,000 to 50 million plaque-forming units (PFU) or placebo.

RESULTS:

No serious vaccine-related adverse events were reported. Mild-to-moderate early-onset reactogenicity was frequent but transient (median, 1 day). Fever was observed in up to 30% of vaccinees. Vaccine viremia was detected within 3 days in 123 of the 130 participants (95%) receiving 3 million PFU or more; rVSV was not detected in saliva or urine. In the second week after injection, arthritis affecting one to four joints developed in 11 of 51 participants (22%) in Geneva, with pain lasting a median of 8 days (interquartile range, 4 to 87); 2 self-limited cases occurred in 60 participants (3%) in Hamburg, Germany, and Kilifi, Kenya. The virus was identified in one synovial-fluid aspirate and in skin vesicles of 2 other vaccinees, showing peripheral viral replication in the second week after immunization. ZEBOV-glycoprotein-specific antibody responses were detected in all the participants, with similar glycoprotein-binding antibody titers but significantly higher neutralizing antibody titers at higher doses. Glycoprotein-binding antibody titers were sustained through 180 days in all participants.

CONCLUSIONS:

In these studies, rVSV-ZEBOV was reactogenic but immunogenic after a single dose and warrants further evaluation for safety and efficacy. (Funded by the Wellcome Trust and others; ClinicalTrials.gov numbers, NCT02283099, NCT02287480, and NCT02296983; Pan African Clinical Trials Registry number, PACTR201411000919191.).

PMID:
25830326
PMCID:
PMC5490784
DOI:
10.1056/NEJMoa1502924
[Indexed for MEDLINE]
Free PMC Article

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