PHASE IB TRIAL OF CYTOMEGALOVIRUS GLYCOPROTEIN B VACCINE

巨细胞病毒糖蛋白 B 疫苗 IB 期试验

• 批准号: 6579263
• 负责人: Paul D Griffiths
• 金额: $ 18.9万
• 依托单位: UNIVERSITY COLLEGE LONDON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-15 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6579263
• 关键词: Herpesviridae vaccine; active immunization; antibody titering; clinical research; clinical trial phase I; cytomegalovirus; dosage; glycoproteins; human subject; human therapy evaluation; longitudinal human study; neutralizing antibody; patient oriented research; transplantation immunology; virus load; virus protein

DESCRIPTION (provided by applicant): Cytomegalovirus (CMV) is an important opportunistic pathogen in transplant recipients, AIDS patients and pregnant women. Glycoprotein B (gB) is a protein found on the surface of CMV which contains the major neutralizing epitopes for this virus. A gB vaccine preparation has been shown to induce levels of neutralizing antibody comparable to those found in naturally infected individuals, but it is not known if such antibodies can protect against CMV infection. Transplant patients represent a unique population because they are challenged with CMV present in the donated organ or reactivated endogenously. We have followed substantial numbers of transplant patients in natural history studies to show that: 1) the quantity of CMV DNA detected by polymerase chain reaction, "CMV load" is the major determinant of CMV disease; 2) preexisting natural immunity can moderate the rate of increase of viral load; 3) CMV disease can be prevented by giving pre-emptive therapy before the viral load reaches high values. We now propose a 3-year study to immunize patients awaiting transplantation with CMV gB vaccine and determine if the antibodies induced can moderate the rate of increase of viral load seen post-transplantation. A total of 140 patients will receive CMV gB vaccination according to a placebo-controlled schedule giving single doses (20 mu/g as studied in normals), double doses and booster doses. Vaccine recipients will be followed to determine the durability of gB-vaccine-induced neutralizing antibody titers. Those patients (estimate 105) who proceed to transplant will be followed with serial measures of CMV load. The rate of increase in viral load will be compared for those who receive vaccine versus those allocated placebo. If a vaccine schedule can be identified which controls viral load, this will be recommended for a phase II placebo-controlled trial of clinical efficacy.

描述（由申请人提供）：巨细胞病毒（CMV）是移植受者、艾滋病患者和孕妇的重要机会致病菌。糖蛋白B（gB）是在CMV表面上发现的蛋白质，其含有该病毒的主要中和表位。已显示gB疫苗制剂诱导的中和抗体水平与自然感染个体中发现的中和抗体水平相当，但尚不清楚此类抗体是否可以保护免受CMV感染。移植患者代表了一个独特的人群，因为他们受到捐赠器官中存在的CMV的挑战或内源性重新激活。我们在自然史研究中对大量移植患者进行了随访，结果表明：1）聚合酶链反应检测到的CMV DNA量，“CMV载量”是CMV疾病的主要决定因素; 2）预先存在的自然免疫可以减缓病毒载量的增加速度; 3）在病毒载量达到高值之前给予先发制人的治疗可以预防CMV疾病。 我们现在提出了一项为期3年的研究，免疫等待移植的患者与CMV gB疫苗，并确定是否诱导的抗体可以缓和移植后看到的病毒载量的增加率。 总共140名患者将根据安慰剂对照的时间表接受CMV gB疫苗接种，给予单次剂量（20 mu/g，如在正常人中研究的）、双次剂量和加强剂量。将对疫苗接种者进行随访，以确定gB疫苗诱导的中和抗体滴度的持久性。那些进行移植的患者（估计105例）将接受CMV负荷的系列测量。将比较接受疫苗的患者与分配安慰剂的患者的病毒载量增加率。如果可以确定控制病毒载量的疫苗接种时间表，则将推荐用于临床疗效的II期安慰剂对照试验。