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: 6493576
• 负责人: Robert Floyd Pass
• 金额: $ 15.71万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6493576
• 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 将通过评估来促进该计划的总体目标 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原因，也是导致脑部疾病的主要原因 引起儿童感音神经性听力损失的有效方法 无法预防孕产妇和先天性感染。疫苗 已经开发出来，但尚未评估预防效果 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尚不确定 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接种 血清阴性孕妇在怀孕前经过充分的检查 其中一些人通过随后的怀孕和新生儿筛查 先天性巨细胞病毒感染。由于何时发布的不确定性 随后会发生怀孕，疫苗后续费用昂贵， 需要对新生儿进行巨细胞病毒感染筛查，但缺乏相关知识 大多数人群的孕产妇和先天性感染率，例如 对于任何疫苗制造商来说，试验可能都太昂贵且风险太大 在不解决某些不确定性的情况下进行。该提案将 展示评估 CMV 功效的有效方法 疫苗，针对患有已证实的人群的产后妇女 妊娠期间母体和先天性 CMV 感染率较高。 UAB 医疗中心两家医院产后病房的妇女将 筛选针对CMV的抗体；将招募 400 名血清阴性女性 疫苗试验已持续两年多。参与者将被随机分配到 按 0、1、6 个月的时间表接受 Chiron CMV gB 疫苗或安慰剂，并且 入组后至少三年随访 CMV 感染情况。 CMV 被膜蛋白 pp50、pp65 和 pp50、pp65 抗体的血清学检测 pp150将用于筛选CMV感染疫苗。前四 在此人群中，超过 65% 的参与者预计会完成 研究期间怀孕；所有新生儿都将接受筛查 用于先天性巨细胞病毒感染。这项研究将定义安全性和 这种 CMV gB 疫苗对产后妇女的免疫原性。此外，它 将允许评估疫苗诱导免疫的持久性 反应（gB 抗体、中和抗体和 CD4 增殖）， 以及免疫反应水平与疗效之间的关系 预防孕产妇感染。它还将定义先天性感染 研究人群中的比率，提供计算所需的数据 测试疫苗功效的试验的样本量 预防先天性巨细胞病毒感染。本次试用将提供样品 详细比较疫苗诱导的免疫与来自免疫的免疫 自然获得性感染，并详细分析其影响 疫苗诱导免疫对病毒学和免疫学反应的影响 感染是项目 2 的重点。