Volume 391, Issue 10120, Pages 563-571 (February 2018) Preliminary aggregate safety and immunogenicity results from three trials of a purified inactivated Zika virus vaccine candidate: phase 1, randomised, double-blind, placebo- controlled clinical trials  Kayvon Modjarrad, MD, Leyi Lin, MD, Sarah L George, MD, Kathryn E Stephenson, MD, Kenneth H Eckels, PhD, Rafael A De La Barrera, MS, Richard G Jarman, PhD, Erica Sondergaard, BS, Janice Tennant, MPH, Jessica L Ansel, BS, Kristin Mills, MD, Michael Koren, MD, Merlin L Robb, MD, Jill Barrett, MPH, Jason Thompson, MS, Alison E Kosel, PhD, Peter Dawson, PhD, Andrew Hale, MD, C Sabrina Tan, MD, Stephen R Walsh, MD, Keith E Meyer, BS, James Brien, PhD, Trevor A Crowell, MD, Azra Blazevic, DVM, Karla Mosby, BS, Rafael A Larocca, PhD, Peter Abbink, PhD, Michael Boyd, BS, Christine A Bricault, PhD, Michael S Seaman, BS, Anne Basil, BS, Melissa Walsh, BS, Veronica Tonwe, MPH, Prof Daniel F Hoft, MD, Prof Stephen J Thomas, MD, Prof Dan H Barouch, MD, Prof Nelson L Michael, MD  The Lancet  Volume 391, Issue 10120, Pages 563-571 (February 2018) DOI: 10.1016/S0140-6736(17)33106-9 Copyright © 2018 Elsevier Ltd Terms and Conditions

Figure 1 Trial profile Participants were enrolled concurrently at the WRAIR, SLU, and BIDMC study sites. The studies were done independently, but aggregated data are presented. WRAIR=Walter Reed Army Institute of Research. SLU=Saint Louis University. BIDMC=Beth Israel Deaconess Medical Center. ZPIV=purified formalin-inactivated Zika virus vaccine. The Lancet 2018 391, 563-571DOI: (10.1016/S0140-6736(17)33106-9) Copyright © 2018 Elsevier Ltd Terms and Conditions

Figure 2 Frequency of local and systemic adverse events within 7 days of vaccination (A) Local injection-site adverse events. (B) Systemic reactogenic adverse events. We used the National Institute of Allergy and Infectious Diseases Division of Microbiology and Infectious Diseases Adult Toxicity Table to grade severity of adverse events. Multiple adverse events could be reported per participant. The Lancet 2018 391, 563-571DOI: (10.1016/S0140-6736(17)33106-9) Copyright © 2018 Elsevier Ltd Terms and Conditions

Figure 3 Zika virus neutralising antibody responses Titres at days 1, 15, 29, 43, and 57 are shown by randomly assigned group (vaccine or placebo) and site. Data points and error bars are slightly offset from the study visit day on the x-axis for visual clarity. WRAIR=Walter Reed Army Institute of Research. ZPIV=purified formalin-inactivated Zika virus vaccine. SLU=Saint Louis University. BIDMC=Beth Israel Deaconess Medical Center. GMT=geometric mean titre. The Lancet 2018 391, 563-571DOI: (10.1016/S0140-6736(17)33106-9) Copyright © 2018 Elsevier Ltd Terms and Conditions

Figure 4 Zika virus protection in mice by passive human antibody transfer (A) Viral loads (log RNA copies per mL) after adoptive transfer of purified IgG from an unvaccinated individual (sham) or two placebo recipients (placebo) and challenge with 102 plaque-forming units of Zika virus in four groups of five virus-naive female Balb/c mice in de-escalating doses (three doses of 200 μL, or one dose of 200 μL, 40 μL, or 0 μL) in 10 μg/mL solution. (B) Viral loads (log RNA copies per mL) after after adoptive transfer of purified IgG from Zika vaccine recipients at Beth Israel Deaconess Medical Center and challenge with 102 plaque-forming units of Zika virus in ten groups of five virus-naive female Balb/c mice. (C) Correlation of protective efficacy with MN50 titre after antibody transfer and before virus challenge. Each dot represents one participant in the Beth Israel Deaconess Medical Center study. ZIKV=Zika virus. Nab=neutralisation antibodies. MN50=50% microneutralisation titre. The Lancet 2018 391, 563-571DOI: (10.1016/S0140-6736(17)33106-9) Copyright © 2018 Elsevier Ltd Terms and Conditions