一种登革热病毒 1 型活病毒人体挑战株的 1 期、开放性评估。
A Phase 1, Open-Label Assessment of a Dengue Virus-1 Live Virus Human Challenge Strain.
机构信息
Institute for Global Health and Translational Science, Department of Microbiology and Immunology, and Department of Public Health and Preventive Medicine, State University of New York, Upstate Medical University, Syracuse, New York, USA.
Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
出版信息
J Infect Dis. 2021 Feb 3;223(2):258-267. doi: 10.1093/infdis/jiaa351.
BACKGROUND
Dengue human infection models (DHIM) have been used as a safe means to test the viability of prophylaxis and therapeutics.
METHODS
A phase 1 study of 12 healthy adult volunteers using a challenge virus, DENV-1-LVHC strain 45AZ5, was performed. A dose escalating design was used to determine the safety and performance profile of the challenge virus. Subjects were evaluated extensively until 28 days and then out to 6 months.
RESULTS
Twelve subjects received the challenge virus: 6 with 0.5 mL of 6.5 × 103 plaque-forming units (PFU)/mL (low-dose group) and 6 with 0.5 mL of 6.5 × 104 PFU/mL (mid-dose group). All except 1 in the low-dose group developed detectable viremia. For all subjects the mean incubation period was 5.9 days (range 5-9 days) and mean time of viremia was 6.8 days (range 3-9 days). Mean peak for all subjects was 1.6 × 107 genome equivalents (GE)/mL (range 4.6 × 103 to 5 × 107 GE/mL). There were no serious adverse events or long-term safety signals noted.
CONCLUSIONS
We conclude that DENV-1-LVHC was well-tolerated, resulted in an uncomplicated dengue illness, and may be a suitable DHIM for therapeutic and prophylactic product testing.
CLINICAL TRIALS REGISTRATION
NCT02372175.
背景
登革热人体感染模型（DHIM）已被用作测试预防和治疗药物可行性的安全手段。
方法
对 12 名健康成年志愿者使用挑战病毒 DENV-1-LVHC 株 45AZ5 进行了一项 1 期研究。采用剂量递增设计来确定挑战病毒的安全性和性能特征。对受试者进行了广泛的评估，直到第 28 天，然后持续到 6 个月。
结果
12 名受试者接受了挑战病毒：6 名接受 0.5 mL 6.5×103 噬菌斑形成单位（PFU）/mL（低剂量组），6 名接受 0.5 mL 6.5×104 PFU/mL（中剂量组）。低剂量组除 1 人外，其余人均出现可检测到的病毒血症。所有受试者的平均潜伏期为 5.9 天（范围 5-9 天），病毒血症平均时间为 6.8 天（范围 3-9 天）。所有受试者的平均峰值为 1.6×107 基因组当量（GE）/mL（范围 4.6×103 至 5×107 GE/mL）。未观察到严重不良事件或长期安全信号。
结论
我们得出结论，DENV-1-LVHC 耐受性良好，导致单纯性登革热疾病，可能是用于治疗和预防产品测试的合适 DHIM。
临床试验注册
NCT02372175。
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