Abstract

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.

中文翻译：

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登革热病毒 1 型活病毒人类挑战菌株的第 1 阶段开放标签评估

摘要

背景

登革热人类感染模型 (DHIM) 已被用作测试预防和治疗可行性的安全手段。

方法

使用挑战病毒 DENV-1-LVHC 株 45AZ5 对 12 名健康成年志愿者进行了第一阶段研究。剂量递增设计用于确定攻击病毒的安全性和性能特征。受试者进行了广泛的评估，直到 28 天，然后持续到 6 个月。

结果

12 名受试者接受了攻击病毒：6 名 0.5 mL 6.5 × 10 ³ PFU/mL（低剂量组）和 6 名 0.5 mL 6.5 × 10 ⁴ PFU/mL（中剂量组） . 除低剂量组中的 1 名外，所有患者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），病毒血症的平均时间为 6.8 天（范围 3-9 天）。所有受试者的平均峰值为 1.6 × 10 ⁷基因组当量 (GE)/mL（范围为 4.6 × 10 ³至 5 × 10 ⁷ GE/mL）。没有发现严重的不良事件或长期安全信号。

结论

我们得出结论，DENV-1-LVHC 具有良好的耐受性，导致简单的登革热疾病，并且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。