Prophlyactic Vaccine for Human Cytomegalovirus

人巨细胞病毒(HCMV)是一组疱疹病毒的典型例子，它广泛存在于所有地理位置和社会经济群体中，在发达国家有50%的成年人感染。人巨细胞病毒感染对某些高危人群很重要。主要关注的领域是：(1)怀孕期间未出生婴儿感染的风险，(2)与儿童一起工作的人感染的风险，以及(3)免疫功能受损的人(例如器官移植患者和艾滋病毒感染者)感染的风险。流行病学研究表明，80%-90%的先天性巨细胞病毒感染的发育中的未出生婴儿在出生后的头几年会表现出一种不同的病理后遗症，可能包括听力损失、视力障碍和智力低下。越来越多的人认为，减少HCMV载量将对先天性HCMV感染的后遗症产生显著影响。事实上，接种疫苗提供了实现这种减少巨细胞病毒载量的最实用的方式。为了开发这样一种疫苗，需要测试基于病毒抗原的配方，以激活保护性细胞和体液反应，以评估其免疫原性。目前还没有针对巨细胞病毒的这种疫苗。在这项应用中，我们试图开发一种预防性疫苗，并在具有免疫活性的转基因小鼠模型上以及在免疫抑制(CD4T细胞缺陷)的条件下测试其有效性。总体策略是使用这种预防性疫苗来刺激细胞(CD8+和CD4+T细胞)和体液对多种HCMV抗原的反应。该疫苗将基于新的嵌合多表位技术，并利用一种新的复制缺陷腺病毒表达系统，该系统最近已被批准用于人类。

Human cytomegalovirus (HCMV) is a classic example of a group of herpes viruses, which is found universally throughout all geographic locations and socioeconomic groups, and infects 50% of adults in developed countries. HCMV infection is important to certain high-risk groups. Major areas of concern are: (1) the risk of infection to unborn baby during pregnancy, (2) the risk of infection to people who work with children, and (3) the risk of infection to immunocompromised persons (e.g. organ transplant patients and HIV-infected individuals). Epidemiological studies have shown that 80%-90% of developing unborn babies who acquire congenital HCMV infection displays a variable pattern of pathological sequelae within the first few years of life that may include hearing loss, vision impairment and mental retardation. There is an increasing argument that a reduction in HCMV load will have a significant effect on the sequelae associated with congenital HCMV infection. Indeed, vaccination provides the most practical modality of achieving such a reduction in HCMV load. To develop such a vaccine, formulation based on viral antigens that activate both protective cellular and humoral responses needs to be tested to assess its immunogenicity. No such vaccine is presently available for HCMV. In this application we have sought to develop a prophylactic vaccine and to test its efficacy in a immunocompetent transgenic mouse model and as well under conditions of immunosuppression (CD4 T cell deficient). The overall strategy is to use this prophylactic vaccine to stimulate the cellular (CD8+ and CD4+ T cells) and humoral responses against multiple HCMV antigens. This vaccine will be based on the novel chimeric polyepitope technology and exploits a novel replication deficient adenovirus expression system which has recently been approved for human use.