高致病性SIV感染的免疫清除
Scott G Hansen1, Michael Piatak, Abigail B Ventura
1Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon 97006, USA.
Nature
|September 13, 2013
概括
已经确定的像艾滋病毒这样的隐形病毒感染是永久性的. 然而,用细胞巨乳病毒载体接种疫苗的 rhesus macaques 逐渐清除了猿类免疫缺陷病毒 (SIV) 感染,这表明病毒根除的可能性.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 基因治疗 基因治疗
背景情况:
- 已确定的lentiviral感染,包括人类免疫缺陷病毒 (HIV) 和猿类免疫缺陷病毒 (SIV),被认为是永久的.
- 目前的抗逆转录病毒疗法和免疫反应可以控制但不能消除这些感染.
- 了解残留病毒是否易受清除对于管理数百万感染艾滋病毒的人来说至关重要.
研究的目的:
- 调查已确定的猿类免疫缺陷病毒 (SIV) 感染的清除潜力.
- 为了确定由 rhesus cytomegalovirus (RhCMV/SIV) 载体引起的免疫反应是否可以导致SIV的逐步消除.
- 评估RhCMV/SIV疫苗在控制和潜在清除病原性lentiviral感染的长期疗效.
主要方法:
- rhesus macaques (RM) 用表达SIV蛋白质的 rhesus cytomegalovirus (RhCMV/SIV) 载体接种了疫苗.
- 接种疫苗的RM受到了致病性SIVmac239菌株的挑战.
- 超敏感测试,包括定量PCR (qPCR) 和反转录的qPCR (qRT-PCR),用于检测血和组织中的病毒RNA和DNA.
- 进行了共同培养分析和血液淋巴细胞的采用转移,以检测具有复制能力的SIV.
主要成果:
- 大约50%的接种疫苗的RM患者表现出对SIVmac239感染的持久,非血流性控制.
- 尽管最初有病毒传播,但受保护的RM最终会随着时间的推移失去所有SIV感染迹象.
- 超敏感测定检测到没有SIVRNA或DNA在受保护的RM的组织中,即使在挑战数月后.
- 通过广泛的共同培养和收养转移研究,在受保护的RM中无法检测到具有复制能力的SIV.
结论:
- 这项研究提供了令人信服的证据,证明了RM病原性lentiviral感染的逐渐清除.
- 持续的效应器记忆T细胞介导的免疫监测,由细胞巨乳病毒载体引起和维护,可能使得lentiviral储存器易受清除.
- 这些发现表明一种潜在的新策略,用于管理甚至根除像艾滋病毒这样的lentiviral感染.
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