Recent Approaches and Strategies in the Generation of Antihuman Cytomegalovirus Vaccines
Recent Approaches and Strategies in the Generation of Antihuman Cytomegalovirus Vaccines
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DOI：
10.1007/978-1-62703-788-4_17
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发表时间：
2014-01-01
期刊：
影响因子：
--
通讯作者：
Britt, William J.
中科院分区：
文献类型：
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作者：
Boppana, Suresh B.;Britt, William J.
在过去的15年里，用于预防与人类巨细胞病毒（HCMV）感染相关疾病的预防性和治疗性疫苗的开发得到了生物医学研究人员和制药公司的相当大的关注，尽管在40多年的文献中已经描述了生产这种疫苗的尝试。先天性HCMV感染和同种异体移植受者感染的自然史研究表明，预防与HCMV感染相关的疾病是可能的，特别是在缺乏先前存在的免疫力而继发更严重疾病的宿主中。提供了对HCMV免疫反应的实质性了解，以及忠实地概括人类感染和免疫方面的几种动物模型，研究人员似乎能够设计和测试候选疫苗。然而，最近关于母体免疫在先天性HCMV感染自然史中的作用的研究，包括认识到先前免疫的妇女被遗传上不同的HCMV毒株再感染发生在血清阳性率高的人群中，已经提出了关于母体人群中保护性免疫性质的几个问题。这一发现与在受孕前对HCMV免疫的妇女的后代中破坏性先天性感染的显著发生率的观察相结合，表明基于对病毒感染的适应性免疫的传统范例的疫苗开发在预防破坏性先天性HCMV感染方面可能价值有限。也许一个更可行的目标将是预防疫苗，以改变同种异体移植受者的HCMV相关疾病。尽管最近对疫苗试验结果的描述被视为寻求HCMV疫苗取得成功的证据，但对这些研究的仔细分析也表明，目前的战略仍需解决主要障碍。
The development of prophylactic and to lesser extent therapeutic vaccines for the prevention of disease associated with human cytomegalovirus (HCMV) infections has received considerable attention from biomedical researchers and pharmaceutical companies over the previous 15 years, even though attempts to produce such vaccines have been described in the literature for over 40 years. Studies of the natural history of congenital HCMV infection and infection in allograft recipients have suggested that prophylaxis of disease associated with HCMV infection could be possible, particularly in hosts at risk for more severe disease secondary to the lack of preexisting immunity. Provided a substantial understanding of immune response to HCMV together with several animal models that faithfully recapitulate aspects of human infection and immunity, investigators seem well positioned to design and test candidate vaccines. Yet more recent studies of the role of a maternal immunity in the natural history of congenital HCMV infection, including the recognition that reinfection of previously immune women by genetically distinct strains of HCMV occur in populations with a high seroprevalence, have raised several questions about the nature of protective immunity in maternal populations. This finding coupled with observations that have documented a significant incidence of damaging congenital infections in offspring of women with immunity to HCMV prior to conception has suggested that vaccine development based on conventional paradigms of adaptive immunity to viral infections may be of limited value in the prevention of damaging congenital HCMV infections. Perhaps a more achievable goal will be prophylactic vaccines to modify HCMV associated disease in allograft transplant recipients. Although recent descriptions of the results from vaccine trials have been heralded as evidence of an emerging success in the quest for a HCMV vaccine, careful analyses of these studies have also revealed that major hurdles remain to be addressed by current strategies.