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应对恶性SIV感染的疫苗
发布日期:2013/10/8      浏览:2314

关键词: 疫苗 恶性SIV感染 免疫

有关用于“人免疫缺陷病毒”(HIV)和“猿免疫缺陷病毒”(SIV)的潜在疫苗的研究工作迄今为止基本上都没有什么成果。这项研究取得了一些进展,因为它利用了最近的一项发现:在感染后的前几个小时到几天时间里,这些病原体似乎对免疫控制或药理清除是脆弱的。用表达SIV病毒的恒河猴巨细胞病毒载体接种的恒河猴,在经过阴道和静脉途径染毒后,对高致病性SIVmac239病毒形成了耐久性抵抗力。一些接种的动物将病毒复制控制了1-3年时间,没有明显证据表明有残留病毒,这提出了一个可能性:由疫苗诱导的免疫反应事实上可能已经消除了最初的感染。

推荐英文摘要

Nature  doi:10.1038/nature12519

Immune clearance of highly pathogenic SIV infection

Scott G. Hansen,  Michael Piatak Jr,  Abigail B. Ventura,  Colette M. Hughes,  Roxanne M. Gilbride,  Julia C. Ford,  Kelli Oswald,  Rebecca Shoemaker,  Yuan Li,  Matthew S. Lewis, Awbrey N. Gilliam,  Guangwu Xu,  Nathan Whizin,  Benjamin J. Burwitz,  Shannon L. Planer, John M. Turner,  Alfred W. Legasse,  Michael K. Axthelm,  Jay A. Nelson,  Klaus Früh,  Jonah B. Sacha,  Jacob D. Estes,  Brandon F. Keele,  Paul T. Edlefsen,  Jeffrey D. Lifson  & Louis J. Picker

Established infections with the human and simian immunodeficiency viruses (HIV and SIV, respectively) are thought to be permanent with even the most effective immune responses and antiretroviral therapies only able to control, but not clear, these infections1, 2, 3, 4. Whether the residual virus that maintains these infections is vulnerable to clearance is a question of central importance to the future management of millions of HIV-infected individuals. We recently reported that approximately 50% of rhesus macaques (RM; Macaca mulatta) vaccinated with SIV protein-expressing rhesus cytomegalovirus (RhCMV/SIV) vectors manifest durable, aviraemic control of infection with the highly pathogenic strain SIVmac239 (ref. 5). Here we show that regardless of the route of challenge, RhCMV/SIV vector-elicited immune responses control SIVmac239 after demonstrable lymphatic and haematogenous viral dissemination, and that replication-competent SIV persists in several sites for weeks to months. Over time, however, protected RM lost signs of SIV infection, showing a consistent lack of measurable plasma- or tissue-associated virus using ultrasensitive assays, and a loss of T-cell reactivity to SIV determinants not in the vaccine. Extensive ultrasensitive quantitative PCR and quantitative PCR with reverse transcription analyses of tissues from RhCMV/SIV vector-protected RM necropsied 69–172?weeks after challenge did not detect SIV RNA or DNA sequences above background levels, and replication-competent SIV was not detected in these RM by extensive co-culture analysis of tissues or by adoptive transfer of 60 million haematolymphoid cells to naive RM. These data provide compelling evidence for progressive clearance of a pathogenic lentiviral infection, and suggest that some lentiviral reservoirs may be susceptible to the continuous effector memory T-cell-mediated immune surveillance elicited and maintained by cytomegalovirus vectors.

 
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