Baculovirus-derived human immunodeficiency virus type 1 virus-like particles activate dendritic cells and induce ex vivo T-cell responses
Baculovirus-derived human immunodeficiency virus type 1 virus-like particles activate dendritic cells and induce ex vivo T-cell responses
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DOI：
10.1128/jvi.00050-06
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发表时间：
2006-09-01
影响因子：
5.4
通讯作者：
Buonaguro, F. M.
中科院分区：
文献类型：
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作者：
Buonaguro, L.;Tornesello, M. L.;Buonaguro, F. M.
我们最近开发了一种候选人类免疫缺陷病毒1型（HIV-1）疫苗模型，该模型基于HIV-1 Pr 55（gag）病毒样颗粒（HIV-VLP），该颗粒在杆状病毒表达系统中产生，并呈现来自乌干达HIV-1的gp 120分子。进化枝A分离株（HIV-VLPAs）。HIV-VLPA显示通过腹膜内和鼻内给药在BALB/c小鼠中诱导全身和粘膜中和抗体以及细胞毒性T淋巴细胞。在本文中，杆状病毒表达的HIV-VLP对人未成熟单核细胞来源的树突状细胞（MDDC）的影响进行了评估。HIV-VLP有效地诱导MDDC的成熟和活化，并优先通过肌动蛋白依赖性巨胞饮和内吞作用并入MDDC。HIV-VLP激活的MDDC显示Th 1和Th 2特异性细胞因子产生增强，并且HIV-VLP对MDDC的作用不通过Toll样受体2和4（TLR 2和-4）信号传导介导。最后，在离体免疫测定中，负载HIV-VLP的MDDC能够在自体人CD 4（+）T细胞中诱导初次和二次应答。我们关于MDDC与杆状病毒HIV-VLP的相互作用和加工的结果使我们深入了解了体内HIV-VLP（A）诱导的免疫反应的机制。
We have recently developed a candidate human immunodeficiency virus type 1 (HIV-1) vaccine model based on HIV-1 Pr55(gag) virus-like particles (HIV-VLPs), produced in a baculovirus expression system and presenting a gp120 molecule from a Ugandan HIV-1 isolate of clade A (HIV-VLPAs). The HIV-VLPAs show the induction in BALB/c mice of systemic and mucosal neutralizing antibodies as well as cytotoxic T lymphocytes, by intraperitoneal as well as intranasal administration. In the present article, the effects of the baculovirus-expressed HIV-VLPs on human immature monocyte-derived dendritic cells (MDDCs) have been evaluated. The HIV-VLPs efficiently induce maturation and activation of MDDCs and are incorporated into MDDCs preferentially via an actin-dependent macropinocytosis and endocytosis. The HIV-VLP-activated MDDCs show enhanced Th1- and Th2-specific cytokine production, and the effects of HIV-VLPs on MDDCs are not mediated through Toll-like receptors 2 and 4 (TLR2 and -4) signaling. Finally, HIV-VLP-loaded MDDCs are able to induce a primary and secondary response in autologous human CD4(+) T cells in an ex vivo immunization assay. Our results on the interaction and processing of baculovirus HIV-VLPs by MDDCs give an insight into the mechanisms underlying the immune response induced by HIV-VLP(A)s in vivo.