University of Pennsylvania, Philadelphia.
Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania.
J Infect Dis. 2019 Jul 2;220(3):400-410. doi: 10.1093/infdis/jiz132.
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.
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.
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.
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.
简单易用且在室温或 2-8°C 下稳定的非活疫苗方法在控制未来埃博拉病毒（EBOV）爆发方面可能具有优势。我们使用一种免疫原性强的 DNA 疫苗，该疫苗可在小动物和非人类灵长类动物中提供针对致命 EBOV 挑战的保护，进行了一项临床研究以评估肌肉内（IM）和新型皮内（ID）DNA 递送来评估两种针对 EBOV 糖蛋白（GP）的 DNA 疫苗候选物（INO-4201 和 INO-4202）的安全性、耐受性和免疫原性。
在一项 I 期临床试验中，评估了候选物 INO-4201 和 INO-4202 单独使用、联合使用或与编码人细胞因子白细胞介素 12 的质粒联合使用，然后使用 CELLECTRA®IM 或 ID 输送装置进行体内电穿孔，评估其安全性、耐受性和免疫原性。
所有 5 种方案的安全性特征均表现为良性，ID 途径的耐受性更好。所有 5 种方案均产生了针对 EBOV GP 的抗体，ID 组的抗体产生速度最快、幅度最大。每种方案均产生了细胞免疫反应。
INO-4201 的 ID 给药具有良好的耐受性，在 2 剂后可达到 100%的血清反应性，并在超过 70%的受试者中引起干扰素-γ T 细胞反应，为不同人群预防 EBOV 提供了一种新方法。临床试验注册。NCT02464670。
