概念测试阶段研究中的HIV-1疫苗诱导免疫力:个案-队列分析
M Juliana McElrath1, Stephen C De Rosa2, Zoe Moodie3
1Vaccine and Infectious Disease Institute and the HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Medicine, The University of Washington, Seattle, WA, USA; Department of Laboratory Medicine, The University of Washington, Seattle, WA, USA.
Lancet (London, England)
|November 18, 2008
概括
该MRKAd5HIV-1 gag/pol/nef疫苗诱导了HIV特定的CD8+T细胞,但没有减少HIV发病率. 未来的艾滋病毒疫苗需要更大的规模或功能多样性的免疫反应.
科学领域:
- 免疫学 免疫学 免疫学
- 疫苗学 疫苗学 疫苗学
- 传染性疾病 传染性疾病
背景情况:
- 步骤研究发现MRKAd5 HIV-1 gag/pol/nef疫苗在降低血病毒血症方面无效,并且与先前存在的腺病毒血清型5 (Ad5) 免疫力男性的HIV-1发病率较高有关.
- 这项研究旨在评估疫苗诱导的免疫力及其在增加感染风险方面的潜在作用.
研究的目的:
- 为了描述由MRKAd5 HIV-1 gag/pol/nef疫苗诱导的HIV特异性T细胞反应.
- 调查先前存在的Ad5免疫,疫苗诱导反应和HIV-1感染风险之间的关联.
主要方法:
- 用干扰素-马ELISPOT和细胞内细胞因子染色试验评估HIV特异性T细胞免疫性.
- 使用流细胞计测量Ad5特异性T细胞和循环激活CD4+T细胞 (Ki-67+/BcL-2(lo)) 表达CCR5.5.
- 使用病例-队列设计来分析疫苗效应和先前存在的Ad5免疫力对感染风险的影响.
主要成果:
- 疫苗MRKAd5在77%的接种者中诱导可检测的干扰素-分泌HIV特异性T细胞,在62%的接种者中识别多个HIV蛋白.
- 在41%的参与者中发现了表达IL-2,IFN-γ或TNF-α的HIV特异性CD4+T细胞,而在73%的参与者中发现了HIV特异性CD8+T细胞.
- 疫苗诱导的免疫反应在艾滋病毒病例和非病例之间没有差异;然而,Ad5特异性T细胞在病例中较低.
结论:
- MRKAd5 HIV-1 gag/pol/nef 疫苗在诱导HIV特异性CD8+ T细胞方面表现出高的免疫性,与此前的研究结果一致.
- 该研究表明,未来的候选艾滋病毒疫苗必须引起比本试验中观察到的更大规模,更广泛或更功能多样性的免疫反应才能有效.
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