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: 6656401
• 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: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6656401
• 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将通过评估来实现该计划的整体目标 测量疫苗预防疫苗功效的策略 先天性CMV感染。虽然先天性巨细胞病毒（CMV） 感染是脑部疾病和领先的主要感染原因 儿童感官听力损失的原因，有效的手段 没有预防母体和先天性感染。疫苗 已经开发了 先天性CMV感染。开发的主要障碍 预防先天性CMV感染的疫苗是如何确定的 进行功效试验。旨在防止先天性CMV的试验 感染将需要大量注册和免疫 怀孕前的血浆孕妇，之后 通过随后的怀孕和筛查新生儿的数量 先天性CMV感染。因为何时 随后的怀孕将发生，疫苗的昂贵随访， 需要筛查新生儿以换取CMV感染，并且缺乏了解 在大多数人群中，孕产妇和先天性感染率，例如 对于任何疫苗制造商而言，试验可能太昂贵且风险 在不解决某些不确定性的情况下进行。该提议将 展示一种评估CMV功效的有效手段 疫苗，针对来自人口的产后妇女的疫苗 怀孕之间的高孕产妇和先天性CMV感染率很高。 UAB医疗中心两家医院的产后病房的妇女将 筛选抗CMV的抗体；将注册400名静态女性 在疫苗试验中超过两年。参与者将被随机 以0,1,6个月的时间表接收Chiron CMV GB疫苗或安慰剂 随后在入学后至少三年内CMV感染。 CMV Tegument蛋白PP50，PP65和 PP150将用于筛选CMV感染的疫苗。四个以前 在这个人群中的工作，预计超过65％的参与者将完成 在研究过程中怀孕；所有新生儿将被筛选 用于先天性CMV感染。这项研究将定义安全性和 产后女性中CMV GB疫苗的免疫原性。另外，它 将允许评估疫苗诱导免疫的耐用性 反应（对GB的抗体，中和抗体和CD4增殖）， 以及免疫反应水平与功效之间的关系 预防母体感染。它也将定义先天性感染 研究人群的比率，提供计算所需的数据 试验的样本量将测试疫苗的功效 预防先天性CMV感染。该试验将提供样品 详细比较疫苗诱导的免疫力，免疫力 自然获得的感染，以及对 疫苗对病毒学和免疫学反应的免疫力对 感染是项目2的重点。