Enhancement of immune response to an antigen delivered by vaccinia virus by displaying the antigen on the surface of intracellular mature virion.
Enhancement of immune response to an antigen delivered by vaccinia virus by displaying the antigen on the surface of intracellular mature virion.
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DOI：
10.1016/j.vaccine.2011.05.088
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发表时间：
2011-07-26
期刊：
影响因子：
5.5
通讯作者：
Xiang, Yan
中科院分区：
文献类型：
--
作者：
Embry, Addie;Meng, Xiangzhi;Cantwell, Angelene;Dube, Peter H.;Xiang, Yan
牛痘病毒（VACV）是天花疫苗，也是传染病和癌症广泛使用的疫苗载体。通过活疫苗接种获得的大多数抗体应答于病毒粒子结构蛋白，包括细胞内成熟病毒粒子（MV）上的许多完整膜蛋白。在这里，我们发现，通过将抗原作为MV的整体膜蛋白掺入VACV，抗体对外源抗原的反应大大增强。我们构建了表达鼠疫杆菌保护抗原LcrV的重组VACV，该抗原未经修饰或与信号肽或与VACV D8蛋白跨膜结构域（LcrV- tm）融合。电镜显示，LcrV-TM在MV表面显示。重要的是，表达LcrV- tm的VACV在小鼠体内引发的抗LcrV抗体滴度明显高于表达其他形式LcrV的病毒。只有用表达lcrv - tm的VACV免疫的小鼠才能免受致命的鼠疫杆菌和VACV WR的攻击。通过与D8跨膜结构域融合的抗原工程可以广泛应用于增强对由VACV载体传递的抗原的免疫应答。这里描述的重组病毒也可以作为开发针对天花和鼠疫的疫苗的基础。
Vaccinia virus (VACV) is the vaccine for smallpox and a widely-used vaccine vector for infectious diseases and cancers. The majority of the antibodies elicited by live VACV vaccination respond to virion structural proteins, including many integral membrane proteins on the intracellular mature virion (MV). Here, we showed that antibody response to an exogenous antigen delivered by VACV was greatly enhanced by incorporating the antigen as an integral membrane protein of MV. We constructed recombinant VACV expressing a Y. pestis protective antigen, LcrV, unmodified or fused with either a signal peptide or with the transmembrane domain of VACV D8 protein (LcrV-TM). Electron microscopy showed that LcrV-TM was displayed on the surface of MV. Importantly, VACV expressing LcrV-TM elicited a significantly higher titer of anti-LcrV antibody in mice than viruses expressing other forms of LcrV. Only mice immunized with LcrV-TM-expressing VACV were protected from lethal Y. pestis and VACV WR challenges. Antigen engineering through fusion with D8 transmembrane domain may be broadly applicable for enhancing the immune response to antigens delivered by a VACV vector. The recombinant virus described here could also serve as the basis for developing a vaccine against both smallpox and plague.
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