一种纯化灭活寨卡病毒候选疫苗三项试验的初步总体安全性和免疫原性结果：1期随机、双盲、安慰剂对照临床试验。
Preliminary aggregate safety and immunogenicity results from three trials of a purified inactivated Zika virus vaccine candidate: phase 1, randomised, double-blind, placebo-controlled clinical trials.
作者信息
Modjarrad Kayvon, Lin Leyi, George Sarah L, Stephenson Kathryn E, Eckels Kenneth H, De La Barrera Rafael A, Jarman Richard G, Sondergaard Erica, Tennant Janice, Ansel Jessica L, Mills Kristin, Koren Michael, Robb Merlin L, Barrett Jill, Thompson Jason, Kosel Alison E, Dawson Peter, Hale Andrew, Tan C Sabrina, Walsh Stephen R, Meyer Keith E, Brien James, Crowell Trevor A, Blazevic Azra, Mosby Karla, Larocca Rafael A, Abbink Peter, Boyd Michael, Bricault Christine A, Seaman Michael S, Basil Anne, Walsh Melissa, Tonwe Veronica, Hoft Daniel F, Thomas Stephen J, Barouch Dan H, Michael Nelson L
机构信息
Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Department of Internal Medicine, Division of Infectious Diseases, Allergy and Immunology, Saint Louis University School of Medicine, Saint Louis, MO, USA; Saint Louis VA Medical Center, Saint Louis, MO, USA.
出版信息
Lancet. 2018 Feb 10;391(10120):563-571. doi: 10.1016/S0140-6736(17)33106-9. Epub 2017 Dec 5.
BACKGROUND
A safe, effective, and rapidly scalable vaccine against Zika virus infection is needed. We developed a purified formalin-inactivated Zika virus vaccine (ZPIV) candidate that showed protection in mice and non-human primates against viraemia after Zika virus challenge. Here we present the preliminary results in human beings.
METHODS
We did three phase 1, placebo-controlled, double-blind trials of ZPIV with aluminium hydroxide adjuvant. In all three studies, healthy adults were randomly assigned by a computer-generated list to receive 5 μg ZPIV or saline placebo, in a ratio of 4:1 at Walter Reed Army Institute of Research, Silver Spring, MD, USA, or of 5:1 at Saint Louis University, Saint Louis, MO, USA, and Beth Israel Deaconess Medical Center, Boston, MA, USA. Vaccinations were given intramuscularly on days 1 and 29. The primary objective was safety and immunogenicity of the ZPIV candidate. We recorded adverse events and Zika virus envelope microneutralisation titres up to day 57. These trials are registered at ClinicalTrials.gov, numbers NCT02963909, NCT02952833, and NCT02937233.
FINDINGS
We enrolled 68 participants between Nov 7, 2016, and Jan 25, 2017. One was excluded and 67 participants received two injections of Zika vaccine (n=55) or placebo (n=12). The vaccine caused only mild to moderate adverse events. The most frequent local effects were pain (n=40 [60%]) or tenderness (n=32 [47%]) at the injection site, and the most frequent systemic reactogenic events were fatigue (29 [43%]), headache (26 [39%]), and malaise (15 [22%]). By day 57, 52 (92%) of vaccine recipients had seroconverted (microneutralisation titre ≥1:10), with peak geometric mean titres seen at day 43 and exceeding protective thresholds seen in animal studies.
INTERPRETATION
The ZPIV candidate was well tolerated and elicited robust neutralising antibody titres in healthy adults.
FUNDING
Departments of the Army and Defense and National Institute of Allergy and Infectious Diseases.
背景
需要一种安全、有效且能快速扩大规模的寨卡病毒感染疫苗。我们研发了一种纯化的福尔马林灭活寨卡病毒疫苗候选物（ZPIV），该候选物在小鼠和非人灵长类动物中经寨卡病毒攻击后显示出对病毒血症的保护作用。在此，我们展示其在人体中的初步结果。
方法
我们对含氢氧化铝佐剂的ZPIV进行了三项1期、安慰剂对照、双盲试验。在所有三项研究中，健康成年人通过计算机生成的列表随机分配，在美国马里兰州银泉市沃尔特里德陆军研究所按4:1的比例接受5μg ZPIV或生理盐水安慰剂，或在美国密苏里州圣路易斯市的圣路易斯大学以及美国马萨诸塞州波士顿市的贝斯以色列女执事医疗中心按5:1的比例接受。分别于第1天和第29天进行肌肉注射。主要目标是评估ZPIV候选物的安全性和免疫原性。我们记录了直至第57天的不良事件和寨卡病毒包膜中和抗体滴度。这些试验已在ClinicalTrials.gov注册，注册号分别为NCT02963909、NCT02952833和NCT02937233。
结果
我们在2016年11月7日至2017年1月25日期间招募了68名参与者。一名被排除，67名参与者接受了两剂寨卡疫苗（n = 55）或安慰剂（n = 12）。该疫苗仅引起轻度至中度不良事件。最常见的局部反应是注射部位疼痛（n = 40 [60%]）或压痛（n = 32 [47%]），最常见的全身反应性事件是疲劳（29 [43%]）、头痛（26 [39%]）和不适（15 [22%]）。到第57天，52名（92%）疫苗接种者发生了血清转化（中和抗体滴度≥1:10），在第43天观察到几何平均滴度峰值，且超过了动物研究中所见的保护阈值。
解读
ZPIV候选物耐受性良好，在健康成年人中引发了强大的中和抗体滴度。
资助
美国陆军和国防部以及国家过敏和传染病研究所。
Zotero 插件