SAFETY AND IMMUNOGENICITY OF OKA/MERCK VARICELLA VIRUS VACCINE IN CHILDREN W/HIV

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。虽然通常被视为“常规”儿童疾病，水痘-带状疱疹病毒是美国儿童疫苗可预防死亡的主要原因（1）。即使是健康的儿童，水痘也会引起严重的并发症，包括继发性细菌感染、肺炎、中枢神经系统和眼部疾病。在HIV感染的儿童中，水痘-带状疱疹病毒可能比健康儿童更容易引起严重的并发症（2，3，4）。洛杉矶儿童医院临床免疫学和变态反应科的经验是，尽管进行了密集的预防工作，但在我们大多数HIV感染患者中仍可能发生野生型VZV的暴露和感染。水痘-带状疱疹免疫球蛋白（VZIG）的被动预防是次优的，因为在患者的一生中，每次暴露都必须重复给药，并且并不总是能够及时通知暴露。我们项目中三名患者的近期经验进一步证明，持续使用IVIG治疗对该患者人群没有保护作用（5）。 Varivax-自1995年以来已在美国获得许可，目前推荐用于所有健康儿童。该疫苗已在免疫系统正常的儿童中进行了广泛研究，并在对照临床试验中显示出在预防或改善疾病方面非常有效（6，7，8，9，10）。无免疫抑制证据的无症状或轻度症状的HIV感染儿童（CDC N1或A1类）的免疫接种数据有限，表明疫苗是安全的，免疫原性和有效的（11）。然而，它目前还没有被批准用于HIV阳性的儿童，他们的T细胞低于正常水平，或者正在接受每月IVIG输注。因此，我们建议在不符合CDC N1或A1级标准的HIV感染儿童中研究Varivax的安全性和免疫原性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Although commonly viewed as "routine" childhood illness, varicella-zoster virus is the leading cause of vaccine preventable deaths in children in United States (1). Even in healthy children, chicken pox can cause serious complications including secondary bacterial infections, pneumonia, and central nervous system and ocular diseases. In HIV-infected children, varicella-zoster virus may cause serious complications more often than in healthy children (2, 3, 4). It has been the experience in the Division of Clinical Immunology and Allergy at Childrens Hospital Los Angeles that despite intense preventive efforts, exposure to and infection with wild-type VZV is likely to occur in a majority of our HIV-infected patients. Passive prophylaxis with varicella-zoster immunoglobulins (VZIG) are suboptimal because administration must be repeated for each exposure in patient's lifetime and timely notification of exposure is not always possible. Recent experience with three patients in our program further demonstrated that ongoing treatment with IVIG is not protective in this patient population (5). Varivax- has been licensed in United States since 1995 and is currently recommended for all healthy children. The vaccine has been extensively studied in children with normal immune system and has shown to be highly effective in preventing or modifying disease in controlled, clinical trials (6, 7, 8, 9, 10). Limited data on immunization of asymptomatic or mildly symptomatic HIV-infected children without evidence of immune suppression (CDC class N1 or A1) indicated that the vaccine is safe, immunogenic, and effective (11). However, it is currently not approved for use in HIV positive children who have lower than normal T-cells or who are receiving monthly IVIG infusions. Thus, we propose to study the safety and immunogenicity of Varivax- in HIV-infected children who do not meet the criteria for CDC class N1 or A1.