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: 6345937
• 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: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6345937
• 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将通过评估为实现方案的总体目标作出贡献 一种衡量疫苗预防效果的策略 先天性巨细胞病毒感染。虽然先天性巨细胞病毒(CMV) 感染是脑部疾病的主要感染原因，也是 儿童感音神经性耳聋的原因及有效治疗方法 无法预防母婴和先天感染。疫苗 已经被开发出来，但没有一种被评估为预防 先天性巨细胞病毒感染。发展中需要克服的主要障碍 预防先天性巨细胞病毒感染的疫苗还不确定如何 进行疗效试验。一项旨在预防先天性巨细胞病毒的试验 感染将需要登记和接种大量 妊娠前血清阴性的孕妇，在充分的 他们中的许多人通过随后的怀孕和新生儿筛查 先天性巨细胞病毒感染。因为不确定什么时候 随后的怀孕将会发生，昂贵的疫苗后续接种， 需要对新生儿进行CMV感染筛查，以及对CMV感染缺乏了解 大多数人群的母体和先天感染率，如 对于任何疫苗制造商来说，试验可能都太昂贵和太冒险 在没有解决一些不确定因素的情况下进行。这项提议将 展示一种评估巨细胞病毒疗效的有效方法 疫苗，针对产后妇女，来自已证实的 孕期母体和先天性巨细胞病毒感染率高。 UAB医疗中心两家医院产后病房的妇女将 接受巨细胞病毒抗体筛查；将有400名血清阴性妇女参加 在两年多的疫苗试验中。参与者将被随机分配到 按0、1、6个月的计划接种中国巨细胞病毒GB疫苗或安慰剂，并 在注册后至少三年内接受CMV感染。 CMV被膜蛋白pp50、pp65和pp2抗体的血清学检测 Pp150将用于筛选巨细胞病毒感染的疫苗。之前的四个 在这一人群中，超过65%的参与者预计将完成 在研究过程中怀孕；所有新生儿都将接受筛查 治疗先天性巨细胞病毒感染。这项研究将定义安全和 巨细胞病毒GB疫苗在产后妇女中的免疫原性。此外，它还 将允许评估疫苗诱导免疫的持久性 应答(GB抗体、中和抗体和CD4增殖)， 免疫应答水平与治疗效果的关系 预防孕产妇感染。它还将定义先天性感染 在研究人群中的比率，提供计算所需的数据 将测试疫苗效力的试验的样本量 预防先天性巨细胞病毒感染。本试验将提供样本 有关疫苗诱导免疫与疫苗免疫的详细比较 并详细分析了自然获得性感染的影响 疫苗诱导的病毒学免疫和免疫应答 感染是项目2的重点。