Prophlyactic Vaccine for Human Cytomegalovirus

人巨细胞病毒（HCMV）是一组疱疹病毒的典型例子，它在所有地理位置和社会经济群体中普遍存在，并感染发达国家50%的成年人。HCMV感染对某些高危人群很重要。主要关注领域如下：（1）怀孕期间未出生婴儿受感染的风险，（2）儿童工作者受感染的风险，以及（3）免疫功能低下者（例如器官移植患者和艾滋病毒感染者）受感染的风险。流行病学研究表明，80%-90%获得先天性HCMV感染的发育中的未出生婴儿在生命的最初几年内表现出不同的病理后遗症模式，可能包括听力损失、视力障碍和智力迟钝。越来越多的观点认为，HCMV载量的减少将对先天性HCMV感染相关的后遗症产生显著影响。事实上，疫苗接种提供了实现HCMV载量减少的最实用的方式。为了开发这样的疫苗，需要测试基于激活保护性细胞和体液应答的病毒抗原的制剂以评估其免疫原性。目前尚无针对HCMV的疫苗。在本申请中，我们试图开发一种预防性疫苗，并在免疫活性转基因小鼠模型中以及在免疫抑制条件下（CD 4 T细胞缺陷）测试其功效。总体策略是使用这种预防性疫苗来刺激针对多种HCMV抗原的细胞（CD 8+和CD 4 + T细胞）和体液应答。该疫苗将基于新的嵌合多表位技术，并利用最近被批准用于人类的新的复制缺陷型腺病毒表达系统。

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.