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

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From: The Lancet(Vol. 391, Issue 10120)
Publisher: Elsevier B.V.
Document Type: Article
Length: 627 words

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Summary Background A safe, effective, and rapidly scalable vaccine against Zika virus infection is needed. We developed a purified formalin-inactivated Zika virus vaccine (ZPIV) candidate that showed protection in mice and non-human primates against viraemia after Zika virus challenge. Here we present the preliminary results in human beings. Methods We did three phase 1, placebo-controlled, double-blind trials of ZPIV with aluminium hydroxide adjuvant. In all three studies, healthy adults were randomly assigned by a computer-generated list to receive 5 [mu]g ZPIV or saline placebo, in a ratio of 4:1 at Walter Reed Army Institute of Research, Silver Spring, MD, USA, or of 5:1 at Saint Louis University, Saint Louis, MO, USA, and Beth Israel Deaconess Medical Center, Boston, MA, USA. Vaccinations were given intramuscularly on days 1 and 29. The primary objective was safety and immunogenicity of the ZPIV candidate. We recorded adverse events and Zika virus envelope microneutralisation titres up to day 57. These trials are registered at, numbers NCT02963909, NCT02952833, and NCT02937233. Findings We enrolled 68 participants between Nov 7, 2016, and Jan 25, 2017. One was excluded and 67 participants received two injections of Zika vaccine (n=55) or placebo (n=12). The vaccine caused only mild to moderate adverse events. The most frequent local effects were pain (n=40 [60%]) or tenderness (n=32 [47%]) at the injection site, and the most frequent systemic reactogenic events were fatigue (29 [43%]), headache (26 [39%]), and malaise (15 [22%]). By day 57, 52 (92%) of vaccine recipients had seroconverted (microneutralisation titre [greater than or equal to]1:10), with peak geometric mean titres seen at day 43 and exceeding protective thresholds seen in animal studies. Interpretation The ZPIV candidate was well tolerated and elicited robust neutralising antibody titres in healthy adults. Funding Departments of the Army and Defense and National Institute of Allergy and Infectious Diseases. Author Affiliation: (a) Walter Reed Army Institute of Research, Silver Spring, MD, USA (b) Department of Internal Medicine, Division of Infectious Diseases, Allergy and Immunology, Saint Louis University School of Medicine, Saint Louis, MO, USA (c) Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, MO, USA (d) Saint Louis VA Medical Center, Saint Louis, MO, USA (e) Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA (f) Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA (g) Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA (h) Emmes Corporation, Rockville, MD, USA (i) University of Vermont Medical Center and Larner College of Medicine, Burlington, VT, USA * Correspondence to: Prof Nelson L Michael, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA (footnote)[Dagger] Contributed equally Byline: Kayvon Modjarrad, MD (a,[Dagger]), Leyi Lin, MD (a,[Dagger]), Sarah L George, MD (b,d,[Dagger]), Kathryn E Stephenson, MD (e,f,[Dagger]), Kenneth H Eckels, PhD (a), Rafael A De La Barrera, MS (a), Richard G Jarman, PhD (a), Erica Sondergaard, BS (a), Janice Tennant, MPH (b), Jessica L Ansel, BS (e), Kristin Mills, MD (a), Michael Koren, MD (a), Merlin L Robb, MD (g), Jill Barrett, MPH (h), Jason Thompson, MS (h), Alison E Kosel, PhD (h), Peter Dawson, PhD (h), Andrew Hale, MD (i), C Sabrina Tan, MD (e), Stephen R Walsh, MD (e), Keith E Meyer, BS (b), James Brien, PhD (c), Trevor A Crowell, MD (g), Azra Blazevic, DVM (b), Karla Mosby, BS (b), Rafael A Larocca, PhD (e), Peter Abbink, PhD (e), Michael Boyd, BS (e), Christine A Bricault, PhD (e), Michael S Seaman, BS (e), Anne Basil, BS (g), Melissa Walsh, BS (g), Veronica Tonwe, MPH (g), Prof Daniel F Hoft, MD (b,d), Prof Stephen J Thomas, MD (a), Prof Dan H Barouch, MD [] (e,f,**), Prof Nelson L Michael, MD [] (a)

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Gale Document Number: GALE|A625698806