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

Scott A Halperin, Rituparna Das, Matthew T Onorato, Kenneth Liu, Jason Martin, Rebecca J Grant-Klein, Rick Nichols, Beth-Ann Coller, Frans A Helmond, Jakub K Simon, V920-012 Study Team, Scott A Halperin, Rituparna Das, Matthew T Onorato, Kenneth Liu, Jason Martin, Rebecca J Grant-Klein, Rick Nichols, Beth-Ann Coller, Frans A Helmond, Jakub K Simon, V920-012 Study Team

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.

Keywords: Ebola; clinical trial; immunogenicity; rVSVΔG-ZEBOV-GP; vaccine.

© 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.

Figures

Figure 1.
Figure 1.
Participant disposition.
Figure 2.
Figure 2.
Antibody responses through 24 months postvaccination by ZEBOV-GP ELISA (A and B) and PRNT (C and D) GMTs (A and C) and seroresponse rates (B and D) in the per-protocol immunogenicity population. N = Number of participants with serology data at 1 or more timepoints according to the treatment to which they were randomized. n = Number of participants contributing to the analysis. Values below the LLOQ (ZEBOV-GP ELISA: <36.11; PRNT: <35) were replaced with ½ LLOQ in GMT calculations. Abbreviations: CI, confidence interval; GMT, geometric mean titer; LLOQ, lower limit of quantification; PRNT, plaque reduction neutralization test; rVSVΔG-ZEBOV-GP, recombinant vesicular stomatitis virus–Zaire Ebola virus envelope glycoprotein vaccine; ZEBOV-GP ELISA, Zaire Ebola virus envelope immunoglobulin G glycoprotein enzyme-linked immunosorbent assay.
Figure 3.
Figure 3.
ZEBOV-GP ELISA (A) and PRNT (B) GMFR by vaccination group in the per-protocol immunogenicity population. Error bars represent 95% CI. The per-protocol immunogenicity population includes all participants who were compliant with the protocol, received vaccination, were seronegative at day 1, and had a serum sample at 1 or more timepoints collected within an acceptable day range. N = Number of participants with serology data at 1 or more timepoints according to the treatment to which they were randomized. n = Number of participants contributing to the analysis. Values below the LLOQ (ZEBOV-GP ELISA: <36.11; PRNT: <35) were replaced with ½ LLOQ in GMT calculations. Abbreviations: CI, confidence interval; GMFR, geometric mean fold rise; GMT, geometric mean titer; LLOQ, lower limit of quantification; PRNT, plaque reduction neutralization test; rVSVΔG-ZEBOV-GP, recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine; ZEBOV-GP ELISA, Zaire Ebola virus envelope glycoprotein immunoglobulin G enzyme-linked immunosorbent assay.

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