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.
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.
Authors: Stephen C De Rosa; Srilatha Edupuganti; Yunda Huang; Xue Han; Marnie Elizaga; Edith Swann; Laura Polakowski; Spyros A Kalams; Michael C Keefer; Janine Maenza; Yiwen Lu; Megan C Wise; Jian Yan; Matthew P Morrow; Amir S Khan; Jean D Boyer; Laurent Humeau; Scott White; Michael Pensiero; Niranjan Y Sardesai; Mark L Bagarazzi; David B Weiner; Guido Ferrari; Georgia D Tomaras; David C Montefiori; Lawrence Corey; M Juliana McElrath Journal: JCI Insight Date: 2020-07-09
Authors: Ami Patel; Emma L Reuschel; Ziyang Xu; Faraz I Zaidi; Kevin Y Kim; Dana P Scott; Janess Mendoza; Stephanie Ramos; Regina Stoltz; Friederike Feldmann; Atsushi Okumura; Kimberly Meade-White; Elaine Haddock; Tina Thomas; Rebecca Rosenke; Jamie Lovaglio; Patrick W Hanley; Greg Saturday; Kar Muthumani; Heinz Feldmann; Laurent M Humeau; Kate E Broderick; David B Weiner Journal: JCI Insight Date: 2021-05-24
Authors: Sophia M Reeder; Emma L Reuschel; Mamadou A Bah; Kun Yun; Nicholas J Tursi; Kevin Y Kim; Jacqueline Chu; Faraz I Zaidi; Ilknur Yilmaz; Robert J Hart; Benjamin Perrin; Ziyang Xu; Laurent Humeau; David B Weiner; Ahmed S I Aly Journal: Vaccines (Basel) Date: 2020-01-10