Immunogenicity, Lot Consistency, and Extended Safety of rVSVΔG-ZEBOV-GP Vaccine: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study in Healthy Adults.

Autor:	Halperin SA; Canadian Center for Vaccinology, Dalhousie University, IWK Health Centre, and Nova Scotia Health Authority, Halifax, Canada., Das R; Merck & Co., Inc., Kenilworth, New Jersey., Onorato MT; Merck & Co., Inc., Kenilworth, New Jersey., Liu K; Merck & Co., Inc., Kenilworth, New Jersey., Martin J; Merck & Co., Inc., Kenilworth, New Jersey., Grant-Klein RJ; Merck & Co., Inc., Kenilworth, New Jersey., Nichols R; NewLink Genetics, Inc., BioProtection Systems, Ames, Iowa., Coller BA; Merck & Co., Inc., Kenilworth, New Jersey., Helmond FA; Merck & Co., Inc., Kenilworth, New Jersey., Simon JK; Merck & Co., Inc., Kenilworth, New Jersey.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2019 Aug 30; Vol. 220 (7), pp. 1127-1135.
DOI:	10.1093/infdis/jiz241
Abstrakt:	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.)
Databáze:	MEDLINE
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