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

Pablo Tebas, Kimberly A. Kraynyak, Ami Patel, Joel N. Maslow, Matthew P. Morrow, Albert J. Sylvester, Dawson Knoblock, Elisabeth Gillespie, Dinah Amante, Trina Racine, Trevor McMullan, Moonsup Jeong, Christine C. Roberts, Young K. Park, Jean Boyer, Kate E. Broderick, Gary P. Kobinger, Mark Bagarazzi, David B. Weiner, Niranjan Y. SardesaiScott M. White

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

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-γT-cell responses in over 70% of subjects, providing a new approach for EBOV prevention in diverse populations. Clinical Trials Registration. NCT02464670.

Original languageEnglish (US)
Article numberjiz132
Pages (from-to)400-410
Number of pages11
JournalJournal of Infectious Diseases
Volume220
Issue number3
DOIs
StatePublished - Jul 2 2019
Externally publishedYes

Keywords

  • clinical trial
  • DNA vaccine
  • Ebola
  • electroporation
  • immunogenicity
  • safety
  • temperature stable

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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