CMV Subunit Vaccine in Young Women at Risk

描述（由申请方提供）：本临床试验将采用II期、随机、安慰剂对照、双盲临床试验，检测巨细胞病毒（CMV）糖蛋白B（gB）疫苗（Aventis Pasteur）与MF 59佐剂（Chiron Vaccines）预防母体CMV感染的有效性。在4家医院的产后病房对健康年轻妇女进行巨细胞病毒抗体筛查。邀请血清反应阴性者参加临床试验。参与者入组并免疫接种（3剂疫苗，0、1和6个月时间表）。参与者在第三剂疫苗接种后三年内每三个月进行一次随访，以筛查CMV感染，收集免疫原性研究样本，识别妊娠和分娩，并收集安全性信息。临床试验参与者出生的所有婴儿在出生时通过病毒培养检测先天性CMV感染。截至2003年8月31日，12 000多名妇女接受了巨细胞病毒抗体筛查，252名受试者参加了筛查。到目前为止，已经发生了28例CMV感染，每年的感染率为6.6%。66名试验参与者中有78例妊娠，54例活产婴儿中有2例先天性CMV感染（3.7%）。这一审判迄今取得的重要成就包括：招募了约三分之二的计划样本，开发了一种新颖，准确和廉价的终点方法（CMV感染）检测用于CMV疫苗临床试验，招募了一个研究人群，其CMV感染率使我们能够积累有史以来研究的最大一组患有原发性CMV感染的健康无症状年轻女性，免疫学和病毒学检测的建立使用将使我们能够从该试验中了解大量关于疫苗是否有效预防母体感染的信息。 具体目标将测试CMV gB/MF 59疫苗预防母体感染的能力，评估试验参与者后代的先天性CMV感染率，确定母体CMV感染是否与流产相关，表征原发性CMV感染的病毒学和免疫学特征，评估CMV疫苗临床试验中终点鉴定的新方法，定义研究疫苗的长期免疫原性（CMV gB抗体、中和抗体和细胞介导的免疫应答），并比较CMV gB/MF 59接种者与安慰剂接种者的不良事件发生率以及局部和全身反应。根据迄今为止的入组情况和试验参与者的CMV感染率，我们预计研究人群中将有60至90例CMV感染和约200例妊娠。有了计划的入组和这些事件发生率，临床试验将达到测试预防母体感染的有效性所需的把握度，并将提供免疫接种是否影响先天性CMV感染率的初步估计。

DESCRIPTION (provided by applicant): This clinical trial will test the efficacy of cytomegalovirus (CMV) glycoprotein B (gB) vaccine (Aventis Pasteur) with MF59 adjuvant (Chiron Vaccines) to prevent maternal CMV infection, using a phase II, randomized, placebo controlled, double-blind clinical trial. Healthy young women are screened for antibody to CMV on the post-partum wards of 4 hospitals. Those who are seronegative are invited to participate in the clinical trial. Participants are enrolled and immunized (3 doses of vaccine, 0, 1 and 6 month schedule). Participants have follow-up visits every three months for three years after the third dose of vaccine in order to screen them for CMV infection, collect samples for immunogenicity studies, identify pregnancies and births, and collect safety information. All infants born to clinical trial participants are tested for congenital CMV infection by virus culture at birth. As of August 31, 2003, over 12,000 women had been screened for antibody to CMV, and 252 subjects enrolled. Twenty-eight CMV infections have occurred so far, a rate of 6.6% per year. There were 78 pregnancies among 66 trial participants, and 2 congenital CMV infections among 54 live births (3.7%). Important accomplishments in this trial to date include: enrolled around two-thirds of planned sample, developed a novel, accurate and inexpensive means of endpoint (CMV infection) detection for CMV vaccine clinical trials, recruited a study population with a CMV infection rate that allows us to accumulate the largest group of healthy asymptomatic young women with primary CMV infection ever studied, established use of immunologic and virologic assays that will allow us to learn a great deal from this trial whether or not vaccine is effective in preventing maternal infections. Specific aims will test the ability of CMV gB/MF59 vaccine to prevent maternal infection, evaluate the rate of congenital CMV infection in offspring of trial participants, determine whether maternal CMV infection is associated with miscarriage, characterize the virologic and immunologic features of primary CMV infections, evaluate novel approaches to end-point identification in CMV vaccine clinical trials, define long-term immunogenicity of study vaccine (antibody to CMV gB, neutralizing antibody and cell mediated immune response) and compare rates of adverse events as well as local and systemic reactions in CMV gB/MF59 recipients to placebo recipients. Based on enrollment to date and the rate of CMV infection in trial participants, we expect to have 60 to 90 CMV infections in the study population and approximately 200 pregnancies. With planned enrollment and these event rates, the clinical trial will achieve the power needed to test efficacy for prevention of maternal infection and will provide a preliminary estimate of whether immunization affects rates of congenital CMV infection.