Phase 1 Randomized Study of a Tetravalent Dengue Purified Inactivated Vaccine in Healthy Adults in the United States.
Phase 1 Randomized Study of a Tetravalent Dengue Purified Inactivated Vaccine in Healthy Adults in the United States.
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DOI：
10.4269/ajtmh.16-0634
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发表时间：
2017-06
期刊：
影响因子：
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通讯作者：
Thomas SJ
中科院分区：
文献类型：
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作者：
Schmidt AC;Lin L;Martinez LJ;Ruck RC;Eckels KH;Collard A;De La Barrera R;Paolino KM;Toussaint JF;Lepine E;Innis BL;Jarman RG;Thomas SJ
在美国大陆进行的一项首次人体、安慰剂对照、随机、双盲、I期试验中，评价了研究用四价登革热纯化灭活疫苗（DPIV）的4种制剂（1或4 μg氢氧化铝（明矾）或1 μg佐剂系统（AS 01 E或AS 03 B））的安全性和免疫原性。将两剂疫苗或安慰剂肌内注射给100名18-39岁的健康成人，间隔4周，以1：1：1：1：1的比例随机接受四种DPIV制剂之一或生理盐水安慰剂。在远离初次接种的9名参与者的亚组中评价了对第三剂的反应。使用50%微量中和试验评估体液免疫原性。所有DPIV制剂均耐受良好。在第二剂疫苗接种后12个月内，未观察到疫苗相关的严重不良事件。在所有DPIV组中，几何平均抗体滴度在第56天达到峰值，在第二次疫苗接种后6个月内下降，然后稳定。在评估加强的九名受试者中，观察到强烈的回忆反应。这些结果支持继续进行这种登革热候选疫苗的临床开发（clinicaltrials.gov：NCT 01666652）。
The safety and immunogenicity of four formulations of an investigational tetravalent dengue purified inactivated vaccine (DPIV), formulated at 1 or 4 μg with aluminum hydroxide (alum) or at 1 μg with an adjuvant system (AS01E or AS03B), were evaluated in a first-time-in-human, placebo-controlled, randomized, observer-blind, phase 1 trial in the continental United States. Two doses of vaccine or placebo were administered intramuscularly 4 weeks apart to 100 healthy adults 18–39 years of age, randomized 1:1:1:1:1 to receive one of four DPIV formulations or saline placebo. The response to a third dose was evaluated in a subset of nine participants remote from primary vaccination. Humoral immunogenicity was assessed using a 50% microneutralization assay. All DPIV formulations were well tolerated. No vaccine-related serious adverse events were observed through 12 months after the second vaccine dose. In all DPIV groups, geometric mean antibody titers peaked at Day 56, waned through 6 months after the second vaccine dose, and then stabilized. In the nine subjects where boosting was evaluated, a strong anamnestic response was observed. These results support continuation of the clinical development of this dengue vaccine candidate (clinicaltrials.gov: NCT01666652).