1. Immunogenicity, Lot Consistency, and Extended Safety of rVSVΔG-ZEBOV-GP Vaccine: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study in Healthy Adults.
- Author
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Halperin SA, Das R, Onorato MT, Liu K, Martin J, Grant-Klein RJ, Nichols R, Coller BA, Helmond FA, and Simon JK
- Subjects
- Adult, Antibodies, Neutralizing analysis, Antibodies, Viral analysis, Double-Blind Method, Ebola Vaccines immunology, Enzyme-Linked Immunosorbent Assay, Female, Follow-Up Studies, Healthy Volunteers, Hemorrhagic Fever, Ebola virology, Humans, Male, Middle Aged, Risk Factors, Treatment Outcome, Viral Envelope Proteins immunology, Ebola Vaccines adverse effects, Ebolavirus immunology, Hemorrhagic Fever, Ebola prevention & control, Immunogenicity, Vaccine immunology, Vaccination
- Abstract
Background: This double-blind study assessed immunogenicity, lot consistency, and safety of recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSVΔG-ZEBOV-GP)., Methods: Healthy adults (N = 1197) were randomized 2:2:2:2:1 to receive 1 of 3 consistency lots of rVSVΔG-ZEBOV-GP (2 × 107 plaque-forming units [pfu]), high-dose 1 × 108 pfu, or placebo. Antibody responses pre-/postvaccination (28 days, 6 months; in a subset [n = 566], months 12, 18, and 24) were measured. post hoc analysis of risk factors associated with arthritis following vaccination was performed., Results: ZEBOV-GP enzyme-linked immunosorbent assay (ELISA) geometric mean titers (GMTs) increased postvaccination in all rVSVΔG-ZEBOV-GP groups by 28 days (>58-fold) and persisted through 24 months. The 3 manufacturing lots demonstrated equivalent immunogenicity at 28 days. Neutralizing antibody GMTs increased by 28 days in all rVSVΔG-ZEBOV-GP groups, peaking at 18 months with no decrease through 24 months. At 28 days, ≥94% of vaccine recipients seroresponded (ZEBOV-GP ELISA, ≥2-fold increase, titer ≥200 EU/mL), with responses persisting at 24 months in ≥91%. Female sex and a history of arthritis were identified as potential risk factors for the development of arthritis postvaccination., Conclusions: Immune responses to rVSVΔG-ZEBOV-GP persisted to 24 months. Immunogenicity and safety results support continued rVSVΔG-ZEBOV-GP development., Clinical Trials Registration: NCT02503202., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2019
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