Résumé
Background Nonlive vaccine approaches that are simple to deliver and stable at room temperature or 2-8 degrees 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 (R) 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-gamma T-cell responses in over 70% of subjects, providing a new approach for EBOV prevention in diverse populations.
Clinical Trials Registration. NCT02464670.
This is the first direct clinical comparison of intramuscular versus intradermal delivery followed by electroporation. Intradermal delivery of a temperature-stable Ebola vaccine was better tolerated and elicited immune responses that equaled or exceeded responses to intramuscular administration in healthy volunteers.