Towards a rational design of an asymptomatic clinical herpes vaccine: the old, the new, and the unknown.
Towards a rational design of an asymptomatic clinical herpes vaccine: the old, the new, and the unknown.
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DOI：
10.1155/2012/187585
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发表时间：
2012
影响因子：
--
通讯作者：
Benmohamed L
中科院分区：
文献类型：
--
作者：
Chentoufi AA;Kritzer E;Yu DM;Nesburn AB;Benmohamed L
控制1型和2型单纯疱疹病毒（HSV-1和HSV-2）大流行的最大希望是开发有效的疫苗。然而，尽管早在20世纪20年代就开始了几次临床试验，但没有任何疫苗被证明足够安全和有效，以保证商业开发。近年来，细胞和分子免疫学的巨大进步刺激了控制疱疹感染和疾病的创造性努力。然而，在采取新的疫苗策略之前，有必要回答两个基本问题：（i）为什么过去的疱疹疫苗失败了？(ii)为什么大多数HSV血清阳性个体（即，无症状个体）是天然“受保护的”，表现出很少或没有复发的临床疾病，而其它HSV血清阳性个体（即，有症状的个体）有频繁的眼部、口面部和/或生殖器疱疹临床发作吗？我们最近发现了几组独立的HSV-1症状性和无症状表位，这些表位被血清阳性症状性个体和无症状个体的CD 4+和CD 8 + T细胞识别。这些无症状表位将为开发新的基于疱疹表位的疫苗策略提供坚实的基础。在这里，我们提供了过去的临床疫苗试验的简要概述，概述了目前的进展，开发新一代的“无症状”的临床疱疹疫苗，并讨论未来的粘膜“无症状”初免-加强疫苗，可以优化局部保护性免疫。
The best hope of controlling the herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) pandemic is the development of an effective vaccine. However, in spite of several clinical trials, starting as early as 1920s, no vaccine has been proven sufficiently safe and efficient to warrant commercial development. In recent years, great strides in cellular and molecular immunology have stimulated creative efforts in controlling herpes infection and disease. However, before moving towards new vaccine strategy, it is necessary to answer two fundamental questions: (i) why past herpes vaccines have failed? (ii) Why the majority of HSV seropositive individuals (i.e., asymptomatic individuals) are naturally “protected” exhibiting few or no recurrent clinical disease, while other HSV seropositive individuals (i.e., symptomatic individuals) have frequent ocular, orofacial, and/or genital herpes clinical episodes? We recently discovered several discrete sets of HSV-1 symptomatic and asymptomatic epitopes recognized by CD4+ and CD8+ T cells from seropositive symptomatic versus asymptomatic individuals. These asymptomatic epitopes will provide a solid foundation for the development of novel herpes epitope-based vaccine strategy. Here we provide a brief overview of past clinical vaccine trials, outline current progress towards developing a new generation “asymptomatic” clinical herpes vaccines, and discuss future mucosal “asymptomatic” prime-boost vaccines that could optimize local protective immunity.
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