Intradermal SynCon® Ebola GP DNA Vaccine Is Temperature Stable and Safely Demonstrates Cellular and Humoral Immunogenicity Advantages in Healthy Volunteers

J Infect Dis. 2019 Jul 2;220(3):400-410. doi: 10.1093/infdis/jiz132.

Abstract

Background: Nonlive vaccine approaches that are simple to deliver and stable at room temperature or 2-8°C could be advantageous in controlling future Ebola virus (EBOV) outbreaks. Using an immunopotent DNA vaccine that generates protection from lethal EBOV challenge in small animals and nonhuman primates, we performed a clinical study to evaluate both intramuscular (IM) and novel intradermal (ID) DNA delivery.

Methods: Two DNA vaccine candidates (INO-4201 and INO-4202) targeting the EBOV glycoprotein (GP) were evaluated for safety, tolerability, and immunogenicity in a phase 1 clinical trial. The candidates were evaluated alone, together, or in combination with plasmid-encoded human cytokine interleukin-12 followed by in vivo electroporation using either the CELLECTRA® IM or ID delivery devices.

Results: The safety profile of all 5 regimens was shown to be benign, with the ID route being better tolerated. Antibodies to EBOV GP were generated by all 5 regimens with the fastest and steepest rise observed in the ID group. Cellular immune responses were generated with every regimen.

Conclusions: ID delivery of INO-4201 was well tolerated and resulted in 100% seroreactivity after 2 doses and elicited interferon-γ T-cell responses in over 70% of subjects, providing a new approach for EBOV prevention in diverse populations. Clinical Trials Registration. NCT02464670.

Keywords: DNA vaccine; Ebola; clinical trial; electroporation; immunogenicity; safety; temperature stable.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / immunology
  • Ebola Vaccines / adverse effects*
  • Ebola Vaccines / immunology*
  • Ebolavirus / immunology
  • Electroporation / methods
  • Female
  • Glycoproteins / immunology
  • Healthy Volunteers
  • Hemorrhagic Fever, Ebola / immunology
  • Humans
  • Immunity, Cellular / immunology*
  • Immunity, Humoral / immunology*
  • Injections, Intradermal / methods
  • Interleukin-12 / immunology
  • Male
  • Middle Aged
  • Temperature
  • Vaccination / methods
  • Vaccines, DNA / adverse effects*
  • Vaccines, DNA / immunology*
  • Young Adult

Substances

  • Antibodies, Viral
  • Ebola Vaccines
  • Glycoproteins
  • Vaccines, DNA
  • Interleukin-12

Associated data

  • ClinicalTrials.gov/NCT02464670