839. ZIKA-001: Safety and Immunogenicity of an Engineered DNA Vaccine Against ZIKA virus infection
Session: Poster Abstract Session: Zika Virus
Thursday, October 5, 2017
Room: Poster Hall CD
Posters
  • IDSA poster (1).pdf (3.0 MB)
  • Background:

    While Zika virus (ZIKV) infection is typically self-limited, congenital birth defects and Guillain-Barré syndrome are well-described. There are no therapies or vaccines against ZIKV infection.

    Methods:

    ZIKA-001 is a phase I, open label, clinical trial designed to evaluate the safety, side effect profile, and immunogenicity of a synthetic, DNA vaccine (GLS-5700) targeting the pre-membrane+envelope proteins (prME) of the virus. Two groups of 20 participants received GLS-5700 at one of two dose levels: 1 mg or 2 mg DNA/dose at 0, 4, and 12 weeks. Vaccine was administered as 0.1 or 0.2 ml (1 or 2 mg) intradermal (ID) injection followed by electroporation (EP) with the CELLECTRA®-3P device

    Results:

    The median age of the 40 participants was 38 (IQR 30-54) years; 60% were female 30% Latino and 78% white. No SAEs have been reported to date. Local minor AEs were injection site pain, redness, swelling and itching that occurred in half of the participants. Systemic adverse events were rare and included headache, myalgias, upper respiratory infections, fatigue/malaise and nausea.

    Four weeks after the first dose 25% vs 60% of the participants in the 1 mg and 2 mg dose seroconverted. By week 6, 2 weeks after the second dose,  the response was 65 and 84% respectively and 2 weeks after the third dose all participants in both dosing groups developed antibodies. At the end of the vaccination period over 60% of vaccinated person neutralized Zika virus in a vero cell assay and greater than 80% on neuronal cell targets. The protective efficacy of the antibodies generated by the vaccine was evaluated in the lethal IFNAR−/− mouse model. After the intraperitoneal administration of 0.1 ml of either baseline, week 14 serum or PBS the animals were challenged with 106 PFUs of ZIKV PR209 isolate. Whereas animals administered PBS (control) or baseline serum succumbed after a median of 5 days, those pretreated with week 14 serum from study participants survived suggesting that the humoral response generated by the vaccine is protective in this model.

    Conclusion:

    Our trial shows for the first time in humans the safety and immunogenicity of an engineered DNA encoding consensus viral protein against ZIKV. Future studies will evaluate the effectiveness of the vaccine.

     

    Pablo Tebas, MD, FIDSA1, Christine C. Roberts, PhD2, Kar Muthumani, PhD3, Emma Reuschel, PhD3, Scott White, PhD4, Amir S. Khan, PhD4, Trina Racine, PhD5, Hyeree Choi, BS3, Faraz Zaidi, BS3, Jean Boyer, PhD4, Sagar Kudchodkar, PhD3, Young K Park, JD2, Sylvie Trottier, MD, PhD6, Celine Remigio, DPT, RN2, Diane Krieger, MD7, Gary P. Kobinger, PhD8, David Weiner, PhD3 and Joel Maslow, MD, PhD2, (1)Univ. of Penn./Div of Infect Dis, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, (2)GeneOne Life Sciences, Philadelphia, PA, (3)Wistar Institute, Philadelphia, PA, (4)Inovio, Philadelphia, PA, (5)Public Health Agency of Canada, Quebec City, QC, Canada, (6)Centre Hospitalier Universitaire de Quebec, Quebec City, QC, Canada, (7)Miami Research Associates, Miami, FL, (8)University of Laval, Quebec City, QC, Canada

    Disclosures:

    P. Tebas, None

    C. C. Roberts, GeneOne: Member , Salary

    K. Muthumani, None

    E. Reuschel, None

    S. White, GeneOne: Member , Salary

    A. S. Khan, Inovio: Employee and Shareholder , Salary and Stock

    T. Racine, None

    H. Choi, None

    F. Zaidi, None

    J. Boyer, Inovio: Employee and Shareholder , Salary and Stock

    S. Kudchodkar, None

    Y. K. Park, GeneOne: Board Member , CEO and Employee , Salary and Stock

    S. Trottier, Canadian Institutes of Health Research: Investigator , Research grant

    C. Remigio, GeneOne: Employee and Shareholder , Salary and Stock

    D. Krieger, None

    G. P. Kobinger, GeneOne: Grant Investigator and Scientific Advisor , Grant recipient and Research support

    D. Weiner, GeneOne: Grant Investigator and Scientific Advisor , Grant recipient , Licensing agreement or royalty and Stock

    J. Maslow, GeneOne: Employee , Salary and Stock

    See more of: Zika Virus
    See more of: Poster Abstract Session
    Previous Abstract | Next Abstract >>

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 4th with the exception of research findings presented at the IDWeek press conferences.