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PCSK9 Hapten Multicopy Displayed onto Carrier Protein Nanoparticle: An Antiatherosclerosis Vaccine
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2019-07-29 00:00:00 , DOI: 10.1021/acsbiomaterials.9b00434 Shasha You 1 , Xiaoyu Guo 1 , Xiaomei Xue 1 , Yongyong Li 2 , Haiqing Dong 2 , Haiying Ji 1 , Ting Hong 1 , Yazhong Wei 1 , Xueyin Shi 1 , Bin He 1
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2019-07-29 00:00:00 , DOI: 10.1021/acsbiomaterials.9b00434 Shasha You 1 , Xiaoyu Guo 1 , Xiaomei Xue 1 , Yongyong Li 2 , Haiqing Dong 2 , Haiying Ji 1 , Ting Hong 1 , Yazhong Wei 1 , Xueyin Shi 1 , Bin He 1
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In recent years, various vaccination strategies have shed new light on the treatment of atherosclerosis. Proprotein convertase subtilisin/Kexin type 9 (PCSK9) is a hot target in the development of antiatherosclerosis vaccine. However, the efficacy of conventional PCSK9 is largely limited by poor immunogenicity and low hapten density. Therefore, we hypothesized whether a nanostructure synthesized by self-assembled carrier protein accompanied by multicopy hapten display could improve the efficacy of vaccine. In this study, bovine serum albumin (BSA) was self-assembled into sub-100 nm nanoparticles via an intermolecular disulfide network as the inner core. Then, sequences of PCSK9 were conjugated onto the surface of nanoparticles by “click” chemistry to consequently form an orderly structured of nanovaccine with repetitive hapten display. Compared with conventional PCSK9 peptide vaccine, our immunization study demonstrated that the PCSK9 multicopy display nanovaccine (PMCDN) was able to induce higher titers of PCSK9 antibody and more efficient lymph node drainage and improve endocytosis by antigen presenting cells.
中文翻译：
PCSK9半抗原多拷贝显示在载体蛋白纳米颗粒上：抗动脉粥样硬化疫苗
近年来，各种疫苗接种策略为动脉粥样硬化的治疗提供了新的思路。前蛋白转化酶枯草杆菌蛋白酶/ Kexin 9型（PCSK9）是抗动脉粥样硬化疫苗开发的热门目标。但是，常规PCSK9的功效在很大程度上受到免疫原性差和半抗原密度低的限制。因此，我们假设由自组装载体蛋白与多拷贝半抗原展示相结合合成的纳米结构是否可以提高疫苗的功效。在这项研究中，牛血清白蛋白（BSA）通过分子间二硫键网络作为内核自组装成100 nm以下的纳米颗粒。然后，通过“点击”化学将PCSK9序列缀合到纳米颗粒的表面上，从而形成具有重复的半抗原展示的有序结构的纳米疫苗。
更新日期：2019-07-29
中文翻译：
PCSK9半抗原多拷贝显示在载体蛋白纳米颗粒上：抗动脉粥样硬化疫苗
近年来，各种疫苗接种策略为动脉粥样硬化的治疗提供了新的思路。前蛋白转化酶枯草杆菌蛋白酶/ Kexin 9型（PCSK9）是抗动脉粥样硬化疫苗开发的热门目标。但是，常规PCSK9的功效在很大程度上受到免疫原性差和半抗原密度低的限制。因此，我们假设由自组装载体蛋白与多拷贝半抗原展示相结合合成的纳米结构是否可以提高疫苗的功效。在这项研究中，牛血清白蛋白（BSA）通过分子间二硫键网络作为内核自组装成100 nm以下的纳米颗粒。然后，通过“点击”化学将PCSK9序列缀合到纳米颗粒的表面上，从而形成具有重复的半抗原展示的有序结构的纳米疫苗。
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