Prevention of Cytomegalovirus Infection

描述（由申请人提供）：胎儿巨细胞病毒（CMV）感染导致每年大约8000名出生的婴儿智力迟钝和/或失聪。这些影响主要是由于怀孕期间母体原发性巨细胞病毒感染。我们和其他人发现，25%至80%的儿童在日托中心感染巨细胞病毒，并在3至41个月（平均18个月）之间脱落病毒。2岁以下受感染儿童的血清阴性母亲中，至少有一半在一年内从子女那里获得巨细胞病毒，而其他血清阴性妇女的年感染率< 5%。有可能控制这种感染的巨细胞病毒疫苗可供评估。预防怀孕期间孕产妇原发性感染的有效国家疫苗接种战略应包括儿童免疫接种。在成人中，我们发现自然血清阳性可以防止再感染。为了确定中和抗体是否影响幼儿巨细胞病毒感染的自然史，我们将在一项扩大的安慰剂对照双盲I-II期安全性和免疫原性试验中评估纯化蛋白疫苗CMV gB/MF59。由于本研究中的婴儿将被纳入日托中心，并且原发性巨细胞病毒感染率很高，因此我们将检验以下假设：接种过疫苗的两岁以下儿童可免受感染，或病毒排泄时间较短，其中一种或另一种与高水平的中和抗体有关。我们将比较在日托中心登记并接种CMV gB/MF59疫苗的两岁以下婴儿的感染率或病毒排泄持续时间与接受安慰剂的匹配血清阴性婴儿的感染率和病毒排泄持续时间。我们还将确定感染或病毒脱落的持续时间是否与婴儿的免疫反应或年龄有关。待测免疫应答参数包括IgG、IgG对CMV gB、中和滴度、免疫印迹表征的IgG应答、CD4+应答细胞频率、粘膜免疫。这项研究的结果将确定是否有可能预防巨细胞病毒感染。

DESCRIPTION (provided by applicant): Infection of the fetus with cytomegalovirus (CMV) results in approximately 8,000 infants born each year who will be mentally retarded and/or deaf. These effects are mainly due to primary maternal CMV infection during pregnancy. We and others have found that between 25% and 80% of children acquire CMV infections in daycare and shed the virus for between 3 and 41 months (mean of 18 months). At least half of seronegative mothers with infected children under age 2 years acquire CMV from their children within one year compared to an annual rate of < 5% among other seronegative women. CMV vaccines with the potential to control this infection are available for evaluation. An effective national vaccination strategy to prevent primary maternal infection during pregnancy should include childhood immunization. In adults we found that natural seropositivity protects against reinfections. To determine neutralizing antibodies are effect the natural history of CMV infection in toddlers, we will evaluate a purified protein vaccine, CMV gB/MF59, in an expanded placebo controlled double blinded phase I-II safety and immunogenicity trial. Because the infants in this study will be enrolled in daycare and will have a high rate of primary CMV infections we will be testing the hypothesis that immunized children less than two years of age are protected against infection or have a reduced duration of viral excretion and one or the other of these will be associated with high levels of neutralizing antibodies. We will compare the infection rate or the duration of viral excretion of infants under two years of age enrolled in daycare and immunized with CMV gB/MF59 vaccine to the infection rate and duration of viral excretion of matched seronegative infants receiving a placebo. We will also determine if infection or the duration of viral shedding are associated with an infant's immune response or age. The parameters of the immune response to be measured will include IgG, IgG to CMV gB, neutralizing titers, IgG responses characterized by immunoblotting, CD4+ responder cell frequencies, and mucosal immunity. The results of this study will establish if prevention of CMV infections is possible.