Randomized Trial of a Vaccine Regimen to Prevent Chronic HCV Infection.
Randomized Trial of a Vaccine Regimen to Prevent Chronic HCV Infection.
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DOI：
10.1056/nejmoa2023345
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发表时间：
2021-02-11
期刊：
影响因子：
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通讯作者：
Cox AL
中科院分区：
文献类型：
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作者：
Page K;Melia MT;Veenhuis RT;Winter M;Rousseau KE;Massaccesi G;Osburn WO;Forman M;Thomas E;Thornton K;Wagner K;Vassilev V;Lin L;Lum PJ;Giudice LC;Stein E;Asher A;Chang S;Gorman R;Ghany MG;Liang TJ;Wierzbicki MR;Scarselli E;Nicosia A;Folgori A;Capone S;Cox AL
预防慢性丙型肝炎病毒（HCV）感染的安全有效的疫苗是消除这种疾病的关键组成部分。在这个1-2期随机、双盲、安慰剂对照试验中，我们评估了重组黑猩猩腺病毒3载体引发疫苗接种，然后是重组改良安卡拉牛痘加强;两种疫苗都编码HCV非结构蛋白。根据近期注射吸毒史被认为有HCV感染风险的成年人在第0天和第56天被随机分配（以1：1的比例）接受疫苗或安慰剂。疫苗相关严重不良事件、严重局部或全身不良事件和实验室不良事件是主要安全性终点。主要疗效终点是慢性丙型肝炎病毒感染，定义为持续6个月的病毒血症。共有548名参与者接受了随机分组，每组274人。两组慢性HCV感染的发生率无显著差异。在符合方案人群中，每组有14名参与者发生慢性HCV感染（风险比[疫苗vs安慰剂]，1.53; 95%置信区间[CI]，0.66至3.55;疫苗有效性，-53%; 95% CI，-255至34）。在改良的意向治疗人群中，疫苗组有19名参与者发生慢性HCV感染，安慰剂组有17名（风险比，1.66; 95%CI，0.79 - 3.50;疫苗有效性，-66%; 95%CI，-250-21）。疫苗组和安慰剂组感染后HCVRNA峰值的几何平均值不同（分别为152.51×103 IU/ml和1804.93×103 IU/ml）。在疫苗组78%的参与者中检测到对HCV的T细胞反应。两组中发生严重不良事件的参与者百分比相似。在这项试验中，HCV疫苗方案没有引起严重的不良事件，产生HCV特异性T细胞应答，并降低了HCV RNA的峰值水平，但它不能预防慢性HCV感染。（由国家过敏和传染病研究所资助; ClinicalTrials.gov编号，NCT 01436357。
A safe and effective vaccine to prevent chronic hepatitis C virus (HCV) infection is a critical component of efforts to eliminate the disease. In this phase 1–2 randomized, double-blind, placebo-controlled trial, we evaluated a recombinant chimpanzee adenovirus 3 vector priming vaccination followed by a recombinant modified vaccinia Ankara boost; both vaccines encode HCV nonstructural proteins. Adults who were considered to be at risk for HCV infection on the basis of a history of recent injection drug use were randomly assigned (in a 1:1 ratio) to receive vaccine or placebo on days 0 and 56. Vaccine-related serious adverse events, severe local or systemic adverse events, and laboratory adverse events were the primary safety end points. The primary efficacy end point was chronic HCV infection, defined as persistent viremia for 6 months. A total of 548 participants underwent randomization, with 274 assigned to each group. There was no significant difference in the incidence of chronic HCV infection between the groups. In the per-protocol population, chronic HCV infection developed in 14 participants in each group (hazard ratio [vaccine vs. placebo], 1.53; 95% confidence interval [CI], 0.66 to 3.55; vaccine efficacy, −53%; 95% CI, −255 to 34). In the modified intention-to-treat population, chronic HCV infection developed in 19 participants in the vaccine group and 17 in placebo group (hazard ratio, 1.66; 95% CI, 0.79 to 3.50; vaccine efficacy, −66%; 95% CI, −250 to 21). The geometric mean peak HCV RNA level after infection differed between the vaccine group and the placebo group (152.51×103 IU per milliliter and 1804.93×103 IU per milliliter, respectively). T-cell responses to HCV were detected in 78% of the participants in the vaccine group. The percentages of participants with serious adverse events were similar in the two groups. In this trial, the HCV vaccine regimen did not cause serious adverse events, produced HCV-specific T-cell responses, and lowered the peak HCV RNA level, but it did not prevent chronic HCV infection. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT01436357.)