来自美国俄勒冈健康与科学大学的研究人员解答了一个持续数十年的秘密:为什么毒性稍加减弱的猴免疫缺陷病毒(SIV)能够阻止具有完全毒性的病毒毒株对猴子的感染,但是这种方法用于人身上则风险性比较高,以及为什么毒性严重受损或完全失活的SIV病毒作为疫苗一点效果都没有。

-2012年11月《自然-医学》

中文翻译


【题目】淋巴结T细胞反应预报SIV减毒活疫苗的效率

【译文】猴免疫缺陷病毒(SIV)减毒活疫苗(LAV)保持着在HIV和AIDS非人灵长类模型中所有疫苗的最强效率,但它们强烈的保护作用基础尚不清楚。本研究表明LAV介导的抵抗静脉内野生型SIVmac239攻击的程度与淋巴结中SIV特异性的、效应因子分化的T细胞功能和强度显著相关,但与血液中这样的T细胞反应以及细胞、体液或固有免疫参数并不相关。我们发现保护性T细胞反应的维持与淋巴结中持续的LAV复制相关,这主要发生在滤泡辅助T细胞中。因此,效应性LAV维持了淋巴组织为基础的、效应因子分化的、SIV特异性的T细胞,这些T细胞会阻断并抑制早期野生型SIV扩增,如果出现的频率充足,还可以完全控制并清除感染,为安全的持续性载体的发展提供了一种理论,这种载体可以诱导并维持这样的反应。

英文原稿


[Title]: Lymph node T cell responses predict the efficacy of live attenuated SIV vaccines

 [Authors]:Yoshinori Fukazawa,1, 2, 8 Haesun Park,1, 2, 8 Mark J Cameron,3 Francois Lefebvre,3 Richard Lum,1, 2 Noel Coombes,1, 2 Eisa Mahyari,1, 2 Shoko I Hagen,1, 2 Michael K Axthelm,1, 2 Adrian McDermott,5 Guido Ferrari,6 David C Montefiori,6 Paul T Edlefsen,7 Michael Piatak Jr,4 Jeffrey D Lifson,4 Rafick P Sékaly3 & Louis J Picker1, 2 et al.

[Abstract]Live attenuated simian immunodeficiency virus (SIV) vaccines (LAVs) remain the most efficacious of all vaccines in nonhuman primate models of HIV and AIDS, yet the basis of their robust protection remains poorly understood. Here we show that the degree of LAV-mediated protection against intravenous wild-type SIVmac239 challenge strongly correlates with the magnitude and function of SIV-specific, effector-differentiated T cells in the lymph node but not with the responses of such T cells in the blood or with other cellular, humoral and innate immune parameters. We found that maintenance of protective T cell responses is associated with persistent LAV replication in the lymph node, which occurs almost exclusively in follicular helper T cells. Thus, effective LAVs maintain lymphoid tissue-based, effector-differentiated, SIV-specific T cells that intercept and suppress early wild-type SIV amplification and, if present in sufficient frequencies, can completely control and perhaps clear infection, an observation that provides a rationale for the development of safe, persistent vectors that can elicit and maintain such responses.

原文地址

http://www.nature.com/nm/journal/v18/n11/abs/nm.2934.html

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