Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine.
Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine.
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DOI：
10.1038/nature10003
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发表时间：
2011-05-26
期刊：
影响因子：
64.8
通讯作者：
Picker, Louis J.
中科院分区：
文献类型：
--
作者：
Hansen, Scott G.;Ford, Julia C.;Lewis, Matthew S.;Ventura, Abigail B.;Hughes, Colette M.;Coyne-Johnson, Lia;Whizin, Nathan;Oswald, Kelli;Shoemaker, Rebecca;Swanson, Tonya;Legasse, Alfred W.;Chiuchiolo, Maria J.;Parks, Christopher L.;Axthelm, Michael K.;Nelson, Jay A.;Jarvis, Michael A.;Piatak, Michael, Jr.;Lifson, Jeffrey D.;Picker, Louis J.
引起艾滋病的慢病毒HIV和SIV有效地逃避宿主免疫，并且一旦建立，这些病毒的感染很少被免疫机制控制。然而，在粘膜暴露后的最初几天，在病毒传播和大量复制之前，感染的最初建立可能更容易受到免疫控制。在这里，我们报告说，SIV疫苗，包括恒河猴巨细胞病毒（RhCMV）载体建立无限期持久，高频率，SIV特异性效应记忆T细胞（TEM）的反应，在恒河猴（RM）的SIV复制的潜在网站和严格控制高致病性SIVmac 239感染后早期粘膜挑战。24个RM中的13个接受单独的RhCMV载体或RhCMV载体随后腺病毒5（Ad 5）载体（与0/9 DNA/Ad 5疫苗接种的RM相比）显示SIV早期完全控制在12/13例RM中，我们观察到长期（≥1年）保护作用，其特征为：1）偶尔出现血浆病毒血症，最终消退; 2）血液和淋巴结单核细胞中主要不可检测的细胞相关病毒载量; 3）效应位点CD 4+记忆T细胞无耗竭; 4）SIVenv特异性抗体（Ab）无诱导或加强;和5）诱导然后丧失对不包括在RhCMV载体中的SIV蛋白（vif）的T细胞应答。保护作用与疫苗接种阶段SIV特异性CD 8 + T细胞反应峰值的大小相关，并且在没有记忆性T细胞反应的情况下发生。值得注意的是，长期RhCMV载体相关的SIV对照对CD 8+或CD 4+淋巴细胞耗竭不敏感，尸检时，细胞相关的SIV仅偶尔在超灵敏测定的检测限下可测量，观察结果表明最终病毒清除的可能性。因此，持续性载体如CMV及其相关的TEM应答可能对有效的HIV/AIDS疫苗有重要贡献。
The AIDS-causing lentiviruses HIV and SIV effectively evade host immunity, and once established, infections with these viruses are only rarely controlled by immunologic mechanisms. However, the initial establishment of infection in the first few days after mucosal exposure, prior to viral dissemination and massive replication, may be more vulnerable to immune control. Here, we report that SIV vaccines that include rhesus cytomegalovirus (RhCMV) vectors establish indefinitely persistent, high frequency, SIV-specific effector-memory T cell (TEM) responses at potential sites of SIV replication in rhesus macaques (RM) and stringently control highly pathogenic SIVmac239 infection early after mucosal challenge. Thirteen of 24 RM receiving either RhCMV vectors alone or RhCMV vectors followed by adenovirus 5 (Ad5) vectors (vs. 0 of 9 DNA/Ad5-vaccinated RM) manifested early complete control of SIV (undetectable plasma virus), and in 12/13 of these RM, we observed long-term (≥1 year) protection characterized by: 1) occasional blips of plasma viremia that ultimately waned; 2) predominantly undetectable cell-associated viral load in blood and lymph node mononuclear cells; 3) no depletion of effector site CD4+ memory T cells; 4) no induction or boosting of SIVenv-specific antibodies (Abs); and 5) induction and then loss of T cell responses to an SIV protein (vif) not included in the RhCMV vectors. Protection correlated with the magnitude of the peak SIV-specific CD8+ T cell responses in the vaccine phase, and occurred without anamnestic T cell responses. Remarkably, long-term RhCMV vector-associated SIV control was insensitive to either CD8+ or CD4+ lymphocyte depletion, and at necropsy, cell-associated SIV was only occasionally measurable at the limit of detection with ultrasensitive assays, observations suggesting the possibility of eventual viral clearance. Thus, persistent vectors such as CMV and their associated TEM responses might significantly contribute to an efficacious HIV/AIDS vaccine.
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影响因子：
5.4
作者：
North, Thomas W.;Higgins, Joanne;Luciw, Paul A.
通讯作者：
Luciw, Paul A.
DOI：
10.1073/pnas.95.15.8869
发表时间：
1998-07-21
影响因子：
11.1
作者：
Chun, TW;Engel, D;Fauci, AS
通讯作者：
Fauci, AS
DOI：
10.1073/pnas.0902628106
发表时间：
2009-09-15
影响因子：
11.1
作者：
Rosati, Margherita;Bergamaschi, Cristina;Pavlakis, George N.
通讯作者：
Pavlakis, George N.
影响因子：
64.5
作者：
ROSENFELD, MA;YOSHIMURA, K;CRYSTAL, RG
通讯作者：
CRYSTAL, RG
DOI：
10.1084/jem.20090356
发表时间：
2009-07-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Okoye A;Park H;Rohankhedkar M;Coyne-Johnson L;Lum R;Walker JM;Planer SL;Legasse AW;Sylwester AW;Piatak M Jr;Lifson JD;Sodora DL;Villinger F;Axthelm MK;Schmitz JE;Picker LJ
通讯作者：
Picker LJ