Immunogenicity of virus-like particles containing modified human immunodeficiency virus envelope proteins.
Immunogenicity of virus-like particles containing modified human immunodeficiency virus envelope proteins.
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含有修饰的人类免疫缺陷病毒包膜蛋白的病毒样颗粒的免疫原性。
DOI：
10.1016/j.vaccine.2007.01.107
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发表时间：
2007
期刊：
影响因子：
5.5
通讯作者：
Kang,Sang-Moo
中科院分区：
文献类型：
--
作者：
Quan,Fu-Shi;Sailaja,Gangadhara;Skountzou,Ioanna;Huang,Chunzi;Vzorov,Andrei;Compans,RichardW;Kang,Sang-Moo
据报道，HIV包膜蛋白（Env）的广泛糖基化和可变环可屏蔽一些中和表位。在这里，我们研究了病毒样颗粒（VLP）中存在的突变HIV Env的免疫原性。我们用猴人类免疫缺陷病毒（SHIV）VLP免疫小鼠，VLP含有糖基化减少的突变HIV Env（3G），可变环缺失突变（dV 1V 2）或两种类型突变的组合（3G-dV 2 -1G），并评估免疫应答。当与野生型SHIV VLP免疫的小鼠相比时，来自接受具有修饰的HIV Env（3G或dV 1V 2）的VLP的小鼠的免疫血清显示针对同源HIV 89.6病毒以及异源病毒的更高中和活性。来自免疫小鼠的淋巴细胞产生HIV Env特异性细胞因子，其中3G-dV 2 -1G突变体产生高水平的细胞因子。有趣的是，发现树突状细胞和B细胞都与VLP相互作用，表明VLP是有效的免疫原。因此，本研究表明，含有修饰的HIV Env的VLP有可能被开发为能够诱导包括中和活性在内的细胞和体液免疫应答的候选疫苗。
Extensive glycosylation and variable loops of the HIV envelope protein (Env) are reported to shield some neutralizing epitopes. Here, we investigated the immunogenicity of mutated HIV Envs presented in virus-like particles (VLPs). We immunized mice with simian human immunodeficiency virus (SHIV) VLPs containing mutant HIV Env with reduced glycosylation (3G), variable loop-deleted mutations (dV1V2), or combinations of both types of mutations (3G-dV2-1G), and evaluated immune responses. Immune sera from mice that received VLPs with modified HIV Envs (3G or dV1V2) showed higher neutralizing activities against the homologous HIV 89.6 virus as well as heterologous viruses when compared with wild type SHIV VLP-immunized mice. Lymphocytes from immunized mice produced HIV Env-specific cytokines, with the 3G-dV2-1G mutant producing high levels of cytokines. Interestingly, both dendritic cells and B cells were found to interact with VLPs suggesting that VLPs are effective immunogens. Therefore, this study suggests that VLPs containing modified HIV Env have the potential to be developed as candidate vaccines capable of inducing cellular and humoral immune responses including neutralizing activities.