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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.)

Developing vaccines for highly pathogenic viruses such as those causing Lassa, Ebola, and Marburg hemorrhagic fevers is a daunting task due to both scientific and logistical constraints. Scientific hurdles to overcome include poorly defined relationships between pathogenicity and protective immune responses, genetic diversity of viruses, and safety in a target population that includes a large number of individuals with compromised immune systems. Logistical obstacles include the requirement for biosafety level-4 containment to study the authentic viruses, the poor public health infrastructure of the endemic disease areas, and the cost of developing these vaccines for use in non-lucrative markets. Recombinant DNA-based vaccine approaches offer promise of overcoming some of these issues. In this review, we consider the status of various recombinant DNA candidate vaccines against Lassa virus and filoviruses which have been tested in animals., (Published by Elsevier B.V.)

• Antibody response correlating with vaccination was used to define seroresponse. • P-values from Fisher's exact test were used to compare definitions of seroresponse. • Two-fold rise and SSCO of 200 EU/mL best differentiated vaccine/placebo recipients. The recombinant vesicular stomatitis virus – Zaire Ebola virus envelope glycoprotein (rVSVΔG-ZEBOV-GP) vaccine is a live recombinant vesicular stomatitis virus (VSV) where the VSV G protein is replaced with ZEBOV-GP. To better understand the immune response after receiving the rVSVΔG-ZEBOV-GP vaccine, the current analyses evaluated different definitions of seroresponse that differentiate vaccine and placebo recipients enrolled in a placebo-controlled clinical trial (PREVAIL; NCT02344407) in which a subset of the study participants had elevated baseline titers. Alternative values for serostatus cutoff (SSCO; 200–500 EU/mL) and/or fold rise (two- to five-fold) were applied to compare their ability to distinguish between participants receiving rVSVΔG-ZEBOV-GP or placebo. The results indicate that an SSCO of 200 EU/mL can be used to define seropositivity at baseline (i.e. pre-vaccination). The use of dual criteria of the same SSCO (200 EU/mL) together with a two-fold rise in antibody level from baseline provided the definition of seroresponse that maximized the statistical significance between vaccine recipients and placebo recipients post-vaccination. Clinical trial registration: NCT02344407. [ABSTRACT FROM AUTHOR]