Prophlyactic Vaccine for Human Cytomegalovirus

人巨细胞病毒（HCMV）是一组疱疹病毒的典型例子，它普遍存在于所有地理位置和社会经济群体中，感染了发达国家50%的成年人。HCMV感染对某些高危人群很重要。令人关切的主要领域有：(1)怀孕期间未出生婴儿的感染风险；(2)从事儿童工作人员的感染风险；(3)免疫功能低下者（如器官移植患者和艾滋病毒感染者）的感染风险。流行病学研究表明，80%-90%获得先天性HCMV感染的未出生婴儿在生命的最初几年内表现出不同类型的病理性后遗症，其中可能包括听力丧失、视力损害和智力迟钝。越来越多的人认为，减少HCMV载量将对先天性HCMV感染相关的后遗症产生重大影响。事实上，疫苗接种提供了实现这种减少HCMV载量的最实用的方式。为了开发这样一种疫苗，需要对基于激活保护性细胞和体液反应的病毒抗原的配方进行测试，以评估其免疫原性。目前还没有针对HCMV的此类疫苗。在这一应用中，我们试图开发一种预防性疫苗，并在具有免疫能力的转基因小鼠模型和免疫抑制（CD4 T细胞缺陷）条件下测试其有效性。总体策略是使用这种预防性疫苗刺激针对多种HCMV抗原的细胞（CD8+和CD4+ T细胞）和体液反应。该疫苗将基于新的嵌合多聚体技术，并利用最近被批准用于人类的一种新的复制缺陷腺病毒表达系统。

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.