PHASE II/II TRIAL OF RECOMBINANT CMV GB VACCINE IN POSTPARTUM WOMEN

重组 CMV GB 疫苗在产后妇女中的 II/II 期试验

• 批准号: 6100271
• 负责人: Robert Floyd Pass
• 金额: $ 18.48万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6100271
• 关键词: Herpesviridae disease; Herpesviridae vaccine; active immunization; clinical research; congenital infection; cytomegalovirus; disease /disorder prevention /control; drug screening /evaluation; female; glycoproteins; human subject; human therapy evaluation; mother /infant health care; neutralizing antibody; placebos; postpartum; recombinant virus; serology /serodiagnosis; vertical transmission; virus protein

Project 1 will contribute to the overall goal of the Program by evaluating a strategy for measuring efficacy of a vaccine for prevention of congenital CMV infection. Although congenital cytomegalovirus (CMV) infection is the leading infectious cause of brain disease and the leading cause of sensorineural hearing loss in children, an effective means of preventing maternal and congenital infection is not available. Vaccines have been developed, but none has been evaluated for efficacy to prevent congenital CMV infection. The major obstacle to overcome in developing vaccines to prevent congenital CMV infection is uncertainty over how to conduct an efficacy trial. A trial aimed at preventing congenital CMV infection would require enrollment and immunization of large numbers of seronegative pregnant women prior to pregnancy, following a sufficient number of them through a subsequent pregnancy and screening newborns for congenital CMV infection. Because of the uncertainty over when the subsequent pregnancy will occur, the costly follow-up of vaccines, the need to screen newborns for CMV infection and the lack of knowledge of the rate of maternal and congenital infection in most populations, such a trial is probably too expensive and risky for any vaccine manufacturer to undertake without resolving some of the uncertainties. This proposal will demonstrate an efficient means of evaluating the efficacy of a CMV vaccine, targeting postpartum women from a population with a demonstrated high rate of maternal and congenital CMV infection between pregnancies. Women on postpartum wards of two hospitals in the UAB Medical Center will be screened for antibody to CMV; 400 seronegative women will be enrolled over two years in the vaccine trial. Participants will be randomized to receive Chiron CMV gB vaccine or placebo on a 0,1,6 month schedule and followed for CMV infection for a minimum of three years after enrollment. A serologic assay for antibody to CMV tegument proteins pp50, pp65 and pp150 will be used to screen vaccines for CMV infection. Four previous work in this population, over 65% of participants are expected to complete a pregnancy during the course of the study; all newborns will be screened for congenital CMV infection. This study will define the safety and immunogenicity of this CMV gB vaccine in postpartum women. In addition, it will allow assessment of the durability of the vaccine induced immune response (antibody to gB, neutralizing antibody and CD4 proliferation), and the relationship between level of immune response and efficacy for prevention of maternal infection. It will also define congenital infection rate in the study population, providing the data needed to calculate sample size for a trial that will test efficacy of a vaccine for prevention of congenital CMV infection. This trial will provide samples for detailed comparison of vaccine induced immunity with immunity from naturally acquired infection, and detailed analysis of the impact of vaccine induced immunity on the virologic and immunologic response to infection that are the focus of Project 2.

项目1将通过评估， 一种衡量疫苗预防疟疾效力的策略 先天性CMV感染虽然先天性巨细胞病毒（CMV） 感染是脑部疾病的主要传染原因， 儿童感音神经性听力损失的原因，一个有效的手段， 没有预防产妇和先天性感染的措施。疫苗 已经开发出来，但没有一个被评估为有效地防止 先天性CMV感染发展中要克服的主要障碍 疫苗，以防止先天性巨细胞病毒感染是不确定的， 进行疗效试验。一项旨在预防先天性CMV的试验 感染将需要大量的登记和免疫， 血清反应阴性的孕妇在怀孕前，经过充分的 其中一些人通过随后的怀孕和新生儿筛查， 先天性CMV感染由于不确定何时 随后的怀孕将发生，昂贵的后续疫苗， 需要筛查新生儿是否有巨细胞病毒感染以及缺乏对巨细胞病毒感染的了解 大多数人口中的孕产妇和先天性感染率， 试验可能过于昂贵和风险，任何疫苗制造商， 不解决一些不确定性。这项建议会 证明评估CMV疗效的有效方法 疫苗，针对产后妇女从人口证明 怀孕期间母体和先天性巨细胞病毒感染率高。 在UAB医疗中心的两家医院的产后病房的妇女将 筛查CMV抗体;将招募400名血清阴性女性 两年多的疫苗试验。受试者将被随机分配至 按0、1、6个月时间表接受Chiron CMV gB疫苗或安慰剂， 在入组后随访CMV感染至少三年。 抗CMV被膜蛋白pp50、pp65和pp65抗体的血清学检测 pp150将用于筛选CMV感染的疫苗。前四 在这一人群中工作，预计超过65%的参与者将完成 研究期间妊娠;将对所有新生儿进行筛查 先天性巨细胞病毒感染这项研究将确定安全性和 该CMV gB疫苗在产后妇女中的免疫原性。此外还 将允许评估疫苗诱导免疫的持久性 应答（抗gB抗体、中和抗体和CD4增殖）， 以及免疫应答水平与对以下疾病的疗效之间的关系： 预防产妇感染。它也将定义先天性感染 研究人群中的比率，提供计算所需的数据 试验的样本量，该试验将测试疫苗对 预防先天性CMV感染。这次试验将提供样本 详细比较疫苗诱导的免疫力与 自然获得性感染，并详细分析其影响， 疫苗诱导的免疫对病毒学和免疫学应答的影响 感染是项目2的重点。