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

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.

In Vivo Delivery of Nucleic Acid-Encoded Monoclonal Antibodies

“…By far the most advanced of these are the adaptive electroporation systems, where a consistency of in vivo DNA delivery and efficiency has been reported [44], representing potential utility for pDNA-mAb delivery, at least preclinically. In the clinic, vaccine delivery via facilitated electroporation has generated impressive data in people [45][46][47]. The delivery technology is discussed in Sect.…”

Synthetic DNA Vaccines Adjuvanted with pIL-33 Drive Liver-Localized T Cells and Provide Protection from Plasmodium Challenge in a Mouse Model

“…The use of the molecular adjuvant pIL-33 increases the immune response to vaccine and protects 100% of animals from blood-stage disease after sporozoite challenge, where non-adjuvanted vaccine protects 70%-88% of animals from blood-stage disease. Potential contributors to this increased protection in the adjuvanted groups are the increase in antigen responsive liver associated T cells, or perhaps a dose-sparing effect of the adjuvant as previously reported for plasmid IL-12 [62,63], resulting in the IL-33 groups showing enhanced cytokine polyfunctionality. Additional dosing and other adjuvant studies remain important.…”

DNA vaccines: prime time is now

“…However, the ID delivery route was dose sparing and promoted more rapid seroconversion (100% seroreactivity) after 2 immunizations. The simplicity, consistency, and tolerability of the ID format appears to exhibit important advantages for vaccine development against emerging and re-emerging pathogens [16 ], and could have a supportive role for the current VSV-ZEBOV vaccine.…”