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

Autor: Jason C. Martin, Matthew T. Onorato, Beth-Ann Coller, Kenneth Liu, Rituparna Das, V Study Team, Rick Nichols, Scott A. Halperin, Rebecca J. Grant-Klein, Jakub K. Simon, Frans A. Helmond
Rok vydání: 2019
Předmět:
Adult
Male
0301 basic medicine
medicine.medical_specialty
Placebo-controlled study
Arthritis
Enzyme-Linked Immunosorbent Assay
immunogenicity
Antibodies
Viral
Placebo
Major Articles and Brief Reports
03 medical and health sciences
Immunogenicity
Vaccine
0302 clinical medicine
Double-Blind Method
Viral Envelope Proteins
Risk Factors
vaccine
Internal medicine
Post-hoc analysis
medicine
Humans
Immunology and Allergy
030212 general & internal medicine
Ebola Vaccines
rVSVΔG-ZEBOV-GP
Neutralizing antibody
Vaccines
biology
business.industry
Immunogenicity
Vaccination
clinical trial
Hemorrhagic Fever
Ebola
Middle Aged
Ebolavirus
medicine.disease
Antibodies
Neutralizing
Healthy Volunteers
Titer
Treatment Outcome
030104 developmental biology
Infectious Diseases
Ebola
biology.protein
Female
business
Follow-Up Studies
Zdroj: The Journal of Infectious Diseases
ISSN: 1537-6613
0022-1899
DOI: 10.1093/infdis/jiz241
Popis: 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.
Immune responses to rVSVΔG-ZEBOV-GP, measured by ZEBOV-GP immunoglobulin G enzyme-linked immunosorbent assay and plaque reduction neutralization test, were robust and persisted up to 24 months. Together with the favorable safety profile, the immunogenicity results support continued rVSVΔG-ZEBOV-GP development.
Databáze: OpenAIRE
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