Safety and immunogenicity of the rVSV∆G-ZEBOV-GP Ebola virus vaccine candidate in healthy adults: a phase 1b randomised, multicentre, double-blind, placebo-controlled, dose-response study  Dr D Gray Heppner, MD, Tracy L Kemp, MPH, Brian K Martin, PhD, William J Ramsey, MD, Richard Nichols, MA, Emily J Dasen, BA, Charles J Link, MD, Rituparna Das, MD, Zhi Jin Xu, PhD, Eric A Sheldon, MD, Teresa A Nowak, BSE, Thomas P Monath, MD DG Heppner, TL Kemp, BK Martin, WJ Ramsey, R Nichols, EJ Dasen, J Fusco, J Crowell, C Link, J Creager, TP Monath, R Das, ZJ Xu, R Klein, T Nowak, E Gerstenberger, R Bliss, EA Sheldon, RA Feldman, Brandon J Essink, WB Smith, L Chu, WM Seger, J Saleh, JL Borders, M Adams Dr D Gray Heppner, MD, Tracy L Kemp, MPH, Brian K Martin, PhD, William J Ramsey, MD, Richard Nichols, MA, Emily J Dasen, BA, Charles J Link, MD, Rituparna Das, MD, Zhi Jin Xu, PhD, Eric A Sheldon, MD, Teresa A Nowak, BSE, Thomas P Monath, MD DG Heppner, TL Kemp, BK Martin, WJ Ramsey, R Nichols, EJ Dasen, J Fusco, J Crowell, C Link, J Creager, TP Monath, R Das, ZJ Xu, R Klein, T Nowak, E Gerstenberger, R Bliss, EA Sheldon, RA Feldman, Brandon J Essink, WB Smith, L Chu, WM Seger, J Saleh, JL Borders, M Adams  The Lancet Infectious Diseases  Volume 17, Issue 8, Pages 854-866 (August 2017) DOI: 10.1016/S1473-3099(17)30313-4 Copyright © 2017 Elsevier Ltd Terms and Conditions

Figure 1 Trial profile 513 participants were randomly assigned; 512 received vaccine or placebo, and 488 completed the final day 360 study visit. PFU=plaque-forming units. rVSVΔG-ZEBOV-GP=recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine. PI=principal investigator. The Lancet Infectious Diseases 2017 17, 854-866DOI: (10.1016/S1473-3099(17)30313-4) Copyright © 2017 Elsevier Ltd Terms and Conditions

Figure 2 Incidence and severity of solicited local and systemic adverse events for day 0–1, 2–7, and 8–14 intervals after injection of rVSVΔG-ZEBOV-GP or placebo Solicited local and systemic adverse events with an incidence of 5% or higher reported in the first 14 days after injection. Each panel presents a specific adverse event. Data are grouped by treatment group and period of onset. Participants with more than one episode (onset to resolution) of an adverse event with different periods of onset are depicted in each period of onset. Thus, the sum of the incidences for the three periods of onset may exceed the incidence of adverse events as presented over day 0–14 in the appendix (pp 9–12). Low-dose (LD) groups (n=276) are the 3 × 103, 3 × 104, 3 × 105, and 3 × 106 plaque-forming units (PFU) doses. High-dose (HD) groups (n=142) are the 9 × 106, 2 ×107, and 1 × 108 PFU doses. The intended clinical dose is 2 × 107 PFU (n=47). Placebo groups (n=94) are combined from cohort 1 (n=74) and cohort 2 (n=20). The Lancet Infectious Diseases 2017 17, 854-866DOI: (10.1016/S1473-3099(17)30313-4) Copyright © 2017 Elsevier Ltd Terms and Conditions

Figure 3 Antibody response on day 0–360 by endpoint ELISA and PRNT60, by geometric mean titres and seroconversion rate Antibody titres were assessed at 0, 7, 14, 28, 56, 84, 180, and 360 days after vaccination by vaccine dose group, as measured by a fully qualified IgG ELISA against the Zaire-Kikwit strain glycoprotein (A), or the 60% plaque reduction neutralisation test (PRNT60) with the vaccine as the challenge virus (B). Seroconversion status is shown for the same time period after vaccination by dose group by IgG ELISA (C) and by PRNT60 (D). Linear trend analysis shows a significant dose response with ELISA (p=0·0003) and PRNT60 (p<0·0001) across the 3 ×103 to 1×108 PFU dose range. At day 28, the 2 × 107 PFU dose response by ELISA was significantly greater than that of the 3 × 103 (p=0·024) and 3 × 104 (p=0·006) PFU doses, and the 2 × 107 PFU dose response by PRNT60 was greater than that of the 3 × 103 (p=0·0010), 3×104 (p=0·0004), and 3 × 105 (p=0·022) PFU doses. PFU=plaque-forming units. The Lancet Infectious Diseases 2017 17, 854-866DOI: (10.1016/S1473-3099(17)30313-4) Copyright © 2017 Elsevier Ltd Terms and Conditions

Figure 4 Individual antibody titres for the 2 × 107 PFU dose group (n=46) (A) IgG ELISA. (B) 60% plaque-reduction neutralisation test (PRNT60). Geometric mean titres are shown for each timepoint; bars indicate 95% CIs. PFU=plaque-forming units. The Lancet Infectious Diseases 2017 17, 854-866DOI: (10.1016/S1473-3099(17)30313-4) Copyright © 2017 Elsevier Ltd Terms and Conditions