疫苗方案预防慢性 HCV 感染的随机试验。
Randomized Trial of a Vaccine Regimen to Prevent Chronic HCV Infection.
机构信息
From the University of New Mexico, Albuquerque (K.P., E.T., K.T., K.W.); Johns Hopkins University, Baltimore (M.T.M., R.T.V., M.W., K.E.R., G.M., W.O.O., M.F., A.L.C.), the Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (S. Chang, R.G.), and the Emmes Company (M.R.W.), Rockville, and the Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda (M.G.G., T.J.L.) - all in Maryland; GSK Vaccines, Rixensart, Belgium (V.V., L.L.); the University of California, San Francisco, San Francisco (P.J.L., L.C.G., E. Stein, A.A.); the Centers for Disease Control and Prevention, Office of Policy, Planning, and Partnerships, Atlanta (A.A.); and ReiThera, Rome (E. Scarselli, A.F., S. Capone), and CEINGE, Naples (A.N.) - both in Italy.
出版信息
N Engl J Med. 2021 Feb 11;384(6):541-549. doi: 10.1056/NEJMoa2023345.
BACKGROUND
A safe and effective vaccine to prevent chronic hepatitis C virus (HCV) infection is a critical component of efforts to eliminate the disease.
METHODS
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.
RESULTS
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 (152.51×10 IU per milliliter and 1804.93×10 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.
CONCLUSIONS
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.).
背景
预防慢性丙型肝炎病毒（HCV）感染的安全有效的疫苗是消除该疾病的重要组成部分。
方法
在这项 1 期至 2 期、随机、双盲、安慰剂对照试验中，我们评估了一种重组黑猩猩腺病毒 3 载体引发疫苗接种，随后进行重组改良安卡拉痘苗加强；这两种疫苗都编码 HCV 非结构蛋白。根据近期注射吸毒史，被认为有感染 HCV 风险的成年人被随机分配（1:1 比例），在第 0 天和第 56 天接受疫苗或安慰剂。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为主要安全性终点。主要疗效终点是慢性 HCV 感染，定义为持续 6 个月的病毒血症。
结果
共有 548 名参与者接受了随机分组，每组 274 人。两组间慢性 HCV 感染的发生率无显著差异。在符合方案人群中，每组各有 14 名参与者发生慢性 HCV 感染（疫苗组与安慰剂组的风险比[疫苗与安慰剂]，1.53；95%置信区间[CI]，0.66 至 3.55；疫苗效力，-53%；95%CI，-255 至 34）。在改良意向治疗人群中，疫苗组有 19 名参与者和安慰剂组有 17 名参与者发生慢性 HCV 感染（风险比，1.66；95%CI，0.79 至 3.50；疫苗效力，-66%；95%CI，-250 至 21）。感染后 HCV RNA 水平的几何平均峰值在疫苗组和安慰剂组之间存在差异（分别为 152.51×10 IU/毫升和 1804.93×10 IU/毫升）。疫苗组 78%的参与者检测到 HCV 特异性 T 细胞反应。两组间严重不良事件的发生率相似。
结论
在这项试验中，HCV 疫苗方案未导致严重不良事件，产生了 HCV 特异性 T 细胞反应，并降低了 HCV RNA 水平的峰值，但未能预防慢性 HCV 感染。（由国家过敏和传染病研究所资助；临床试验.gov 编号，NCT01436357）。
Zotero 插件