通过无针注射递送的汉坦病毒和普马拉病毒DNA疫苗的1期临床试验。

Phase 1 clinical trial of Hantaan and Puumala virus DNA vaccines delivered by needle-free injection.

作者信息

Hooper Jay W, Kwilas Steven A, Josleyn Matthew, Norris Sarah, Hutter Jack N, Hamer Melinda, Livezey Jeffrey, Paolino Kristopher, Twomey Patrick, Koren Michael, Keiser Paul, Moon James E, Nwaeze Ugo, Koontz Jason, Ledesma-Feliciano Carmen, Landry Nathalie, Wellington Trevor

机构信息

Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, 21702, USA.

Clinical Trials Center, Walter Reed Army Institute of Research, Silver Spring, MD, 20910, USA.

出版信息

NPJ Vaccines. 2024 Nov 17;9(1):221. doi: 10.1038/s41541-024-00998-7.

Hantaan virus (HTNV) and Puumala virus (PUUV) are pathogenic zoonoses found in Asia and Europe, respectively. We conducted a randomized Phase 1 clinical trial of individual HTNV and PUUV DNA vaccines targeting the envelope glycoproteins (GnGc), as well as a combined HTNV/PUUV DNA vaccine delivered at varying doses using the PharmaJet Stratis® needle-free injection system (NCT02776761). Cohort 1 and 2 vaccines consisted of 2 mg/vaccination of HTNV or PUUV plasmid, respectively. Cohort 3 vaccine consisted of 2 mg/vaccination of 1:1 mixture of HTNV and PUUV vaccines. Vaccinations were administered on Days 0, 28, 56, and 168. The vaccines were safe and well tolerated. Neutralizing antibody responses were elicited in 7/7 (100%) subjects who received the HTNV DNA (Cohort 1) and 6/6 (100%) subjects who received the PUUV DNA (Cohort 2) vaccines alone. The combination vaccine resulted in 4/9 (44%) seroconversion against both viruses. After the first two vaccinations, the seroconversion rates for the HTNV and PUUV vaccines were >80%.

汉坦病毒（HTNV）和普马拉病毒（PUUV）分别是在亚洲和欧洲发现的致病性人畜共患病原体。我们针对包膜糖蛋白（GnGc）开展了一项关于单个HTNV和PUUV DNA疫苗以及使用PharmaJet Stratis®无针注射系统以不同剂量递送的联合HTNV/PUUV DNA疫苗的1期随机临床试验（NCT02776761）。第1组和第2组疫苗分别由每次接种2mg的HTNV或PUUV质粒组成。第3组疫苗由每次接种2mg的HTNV和PUUV疫苗1:1混合物组成。在第0、28、56和168天进行接种。这些疫苗安全且耐受性良好。单独接受HTNV DNA疫苗（第1组）的7/7（100%）受试者和接受PUUV DNA疫苗（第2组）的6/6（100%）受试者产生了中和抗体反应。联合疫苗导致4/9（44%）的受试者对两种病毒均发生血清转化。在前两次接种后，HTNV和PUUV疫苗的血清转化率均>80%。