MUCOSAL IMMUNITY & REPLICATION OF HUMAN CYTOMEGALOVIRUS

在美国，人类巨细胞病毒（HCMV）相关疾病每年造成的医疗费用超过100亿美元。先天性巨细胞病毒感染导致的智力迟钝和听力障碍，以及器官移植排斥反应和MDS相关的巨细胞病毒视网膜炎和结肠炎是可预防的疾病。然而，目前还没有预防HCMV疾病的疫苗，大多数灭活或亚基方法都失败了。Aviron的目标是开发一种安全、活、减毒的HCMV疫苗，用于儿童普遍免疫。在器官移植或HIV感染的免疫抑制之前，对血清阴性的人接种疫苗也可以预防免疫受损宿主严重HCMV疾病的发病率和死亡率。在i期SBIR申请中提出的研究目标是应用最近在粘膜疫苗递送和病毒检测方面的创新进展，以了解人类宿主对急性巨细胞病毒感染和免疫的反应。这些数据将用于确定一组四种专门设计的重组活HCMV候选疫苗，当被递送到鼻腔、口腔粘膜表面时，是否会引起体液和细胞反应，从而可能提供保护，免受HCMV感染的后遗症。拟议的商业应用：一种有效的HCMV减毒活疫苗可以预防与HCMV先天性疾病相关的智力迟钝和听力障碍。目前还没有预防或治疗方案可以减少HCMV先天性疾病，因此，HCMV活疫苗解决了一个未满足的公共卫生问题

Human cytomegalovirus (HCMV) associated disease is responsible for over $10 billion in healthcare costs annually in the US. Mental retardation and hearing impairment caused by congenital CMV infection, and organ transplant rejection and MDS associated CMV retinitis and colitis are preventable diseases. However, no vaccine currently exists for prevention of HCMV disease and most inactivated or subunit approaches have failed. Aviron's objective is to develop a safe, live, attenuated HCMV vaccine for universal childhood immunization. Vaccination of seronegative persons prior to immunosuppression for organ transplantation or HIV infection may also prevent the morbidity and mortality of severe HCMV disease in the immunocompromised host. The goal of the research proposed in the Phase l SBIR application is to apply recent innovative advances in mucoaal vaccine delivery and virus detection to understand the human host's response to acute CMV infection and immunization. These data will be used to determine if a set of four specifically designed, reombinant, live HCMV vaccine candidates when delivered to the naso-, oral mucosal surface elicits humoral and cell-based responses that are likely to provide protection from the sequelae of HCMV infection. PROPOSED COMMERCIAL APPLICATIONS: An effective, live attenuated HCMV vaccine should prevent mental retardation and hearing impairment associated with HCMV congenital disease. There are no preventative or therapeutic regimens available to reduce HCMV congenital disease, therefore, the live HCMV vaccine addresses an unmet public health