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Published on: October 17, 2018
Randomized Trial of Vaccines for Zaire Ebola Virus Disease
, Mark Kieh1, Laura Richert1
1From the Partnership for Research on Ebola Virus in Liberia, Monrovia (M.K., S.B.K.); Unité 1219, Bordeaux Population Health, Inria, Statistics in System Biology and Translational Medicine (L.R., E.L.), Euclid-French Clinical Research Infrastructure Network Clinical Trials Platform (L.R., E.L., C.R., G.C.), University of Bordeaux, INSERM, Institut Bergonié, Centre Hospitalier Universitaire de Bordeaux, Clinical Investigation Center-Clinical Epidemiology 1401, Bordeaux (L.R., E.L., C.R., G.C.), INSERM (E.D., R.V., H.E., A.D., A.W., Y.L., Y.Y.), ANRS Emerging Infectious Diseases (France Recherche Nord&Sud Sida-HIV Hépatites) (E.D., A.D., Y.Y.), and Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, Service de Maladies Infectieuses et Tropicales (E.D., Y.Y.), Paris, and the Vaccine Research Institute, Université Paris-Est Créteil, Henri Mondor Hospital, Créteil (A.W., Y.L.) - all in France; Centre National de Formation et de Recherche en Santé Rurale de Mafèrinyah, Maferinyah, Guinea (A.H.B.); the Schools of Public Health (D.W., J.N.) and Statistics (B. Grund), University of Minnesota, Minneapolis; the College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown (B.L., M.S., G.F.D.); University Clinical Research Center, University of Sciences, Techniques, and Technologies of Bamako (S.D.), and Centre pour le Développement des Vaccins, Ministère de la Santé (M.D.), Bamako, Mali; the Center for Vaccine Development and Global Health, University of Maryland, Baltimore (S.S.), and the National Institute of Allergy and Infectious Diseases, Bethesda (J.P., B.D.-K., L.H., H.C.L.) - both in Maryland; Département de Sociologie, Faculté des Lettres et Sciences Humaines, Université Cheikh Anta Diop (S.F.), and the Alliance for International Medical Action (N.P.M., A.M.C.) - both in Dakar, Senegal; London School of Hygiene and Tropical Medicine, London (S.L., D.W.-J., P.P., B. Greenwood); Janssen Vaccines and Prevention, Leiden, the Netherlands (C.M.); and Merck Sharp and Dohme, Kenilworth, NJ (J.S.).
Background:
Questions remain concerning the rapidity of immune responses and the durability and safety of vaccines used to prevent Zaire Ebola virus disease.
Methods:
We conducted two randomized, placebo-controlled trials - one involving adults and one involving children - to evaluate the safety and immune responses of three vaccine regimens against Zaire Ebola virus disease: Ad26.ZEBOV followed by MVA-BN-Filo 56 days later (the Ad26-MVA group), rVSVΔG-ZEBOV-GP followed by placebo 56 days later (the rVSV group), and rVSVΔG-ZEBOV-GP followed by rVSVΔG-ZEBOV-GP 56 days later (the rVSV-booster group). The primary end point was antibody response at 12 months, defined as having both a 12-month antibody concentration of at least 200 enzyme-linked immunosorbent assay units (EU) per milliliter and an increase from baseline in the antibody concentration by at least a factor of 4.
Results:
A total of 1400 adults and 1401 children underwent randomization. Among both adults and children, the incidence of injection-site reactions and symptoms (e.g., feverishness and headache) was higher in the week after receipt of the primary and second or booster vaccinations than after receipt of placebo but not at later time points. These events were largely low-grade. At month 12, a total of 41% of adults (titer, 401 EU per milliliter) and 78% of children (titer, 828 EU per milliliter) had a response in the Ad26-MVA group; 76% (titer, 992 EU per milliliter) and 87% (titer, 1415 EU per milliliter), respectively, had a response in the rVSV group; 81% (titer, 1037 EU per milliliter) and 93% (titer, 1745 EU per milliliter), respectively, had a response in the rVSV-booster group; and 3% (titer, 93 EU per milliliter) and 4% (titer, 67 EU per milliliter), respectively, had a response in the placebo group (P<0.001 for all comparisons of vaccine with placebo). In both adults and children, antibody responses with vaccine differed from those with placebo beginning on day 14.
Conclusions:
No safety concerns were identified in this trial. With all three vaccine regimens, immune responses were seen from day 14 through month 12. (Funded by the National Institutes of Health and others; PREVAC ClinicalTrials.gov number, NCT02876328; EudraCT numbers, 2017-001798-18 and 2017-001798-18/3rd; and Pan African Clinical Trials Registry number, PACTR201712002760250.).
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