PNAS暴露前预防(PrEP)数据分析抗艾滋病病毒免疫应答与感染...

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http://www.bio1000.com/gnjz/immunology/504186.html

美国加州大学旧金山分校一项研究发现，对来自2007年的一项针对艾滋病病毒的暴露前预防(PrEP)试验的免疫应答数据的分析提示了在1型艾滋病病毒抗原特异性免疫应答与暴露在这种病毒中的人们的感染风险有联系。已经有了关于暴露在这种病毒中的未感染者对1型艾滋病病毒的免疫应答的记载，但是这类应答和之后的感染风险之间的联系尚不清楚。Peter Kuebler及其同事比较了两组外周血单核细胞样本出现的针对一组1型艾滋病病毒抗原的免疫应答，其中84份样本是在2007年的一场暴露前预防(PrEP)试验招募的男性的感染前收集的，这些男性在加入这场使用抗艾滋病病毒药物Truvada的试验之后变为血清阳性，480份样本来自在整个试验中保持血清阴性的男性，包括那些服用了药物或者安慰剂的男性。与血清转化的人相比，t细胞对发病机理相关1型艾滋病病毒抗原Gag、Nef、整合酶以及Vif的应答——这是由细胞活素IFN-γ的水平表明的——在保持血清阴性的人体内显著更高。此外，Vif特异性T细胞应答与整合酶特异性T细胞应答每增加到原来的10倍，就与感染风险分别减少64%和48%有关联。发现了分泌IFN-γ的细胞多数是T细胞的CD4+ 或CD8+效应记忆型细胞。这组作者说，需要一项前瞻性研究从而确立抗1型艾滋病病毒保护性免疫的相关性，但是在暴露前预防(PrEP)试验的未感染者中发现抗原特异性、风险相关的免疫应答可能有助于设计预防性疫苗的举措。

原文链接：

Cellular immune correlates analysis of an HIV-1 preexposure prophylaxis trial

原文摘要：

HIV-1–specific T-cell responses in exposed seronegative subjects suggest that a viral breach of the exposure site is more common than current transmission rates would suggest and that host immunity can extinguish subsequent infection foci. The Preexposure Prophylaxis Initiative (iPrEx) chemoprophylaxis trial provided an opportunity to rigorously investigate these responses in a case–control immunology study; 84 preinfection peripheral blood mononuclear cell samples from individuals enrolled in the iPrEx trial who later seroconverted were matched with 480 samples from enrolled subjects who remained seronegative from both the placebo and active treatment arms. T-cell responses to HIV-1 Gag, Protease, Integrase, Reverse Transcriptase, Vif, and Nef antigens were quantified for all subjects in an IFN-γ enzyme-linked immunospot (Elispot) assay. IFN-γ responses varied in magnitude and frequency across subjects. A positive response was more prevalent in those who remained persistently HIV-1–negative for Gag (P = 0.007), Integrase (P < 0.001), Vif (P < 0.001), and Nef (P < 0.001). When correlated with outcomes in the iPrEx trial, Vif- and Integrase-specific T-cell responses were associated with reduced HIV-1 infection risk [hazard ratio (HR) = 0.36, 95% confidence interval (95% CI) = 0.19–0.66 and HR = 0.52, 95% CI = 0.28–0.96, respectively]. Antigen-specific responses were independent of emtricitabine/tenofovir disoproxil fumarate use. IFN-γ secretion in the ELISpot was confirmed using multiparametric flow cytometry and largely attributed to effector memory CD4+ or CD8+ T cells. Our results show that HIV-1–specific T-cell immunity can be detected in exposed but uninfected individuals and that these T-cell responses can differentiate individuals according to infection outcomes.

doi: 10.1073/PNAS.1501443112

marine0425030

多谢分享，前段时间回国办婚礼了。呵呵。。

PNAS啊。。不过结果和概念都不是很新，好就好在他们的样品！