Artificially designed recombinant protein composed of multiple epitopes of foot-and-mouth disease virus as a vaccine candidate.
Artificially designed recombinant protein composed of multiple epitopes of foot-and-mouth disease virus as a vaccine candidate.
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DOI：
10.1186/s12934-017-0648-2
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发表时间：
2017-02-22
影响因子：
6.4
通讯作者：
Choi YJ
中科院分区：
文献类型：
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作者：
Lee HB;Piao DC;Lee JY;Choi JY;Bok JD;Cho CS;Kang SK;Choi YJ
由于口蹄疫灭活疫苗是由口蹄疫活病毒（FMDV）培养而成，因此其安全性受到关注。为了克服这个问题，重组蛋白已被研究作为替代疫苗。我们设计了一种嵌合的多表位重组蛋白（5 BT），其由来自不同FMDV变体的5个B细胞表位（VP 1的136-162残基）和1个T细胞表位（3A的21-35残基）的串联重复序列组成。为了增加5 BT的溶解度和稳定性，将其与BmpB（Brachyspira hyocytteriae（B5 BT）的膜蛋白B）缀合。我们的研究结果表明，5 BT是容易被降解的宿主蛋白酶，并产生了相当大比例的包涵体。通过与BmpB缀合，5 BT的稳定性和溶解性大大增加。用5 BT和B5 BT免疫的小鼠血清中观察到FMDV特异性抗体，与灭活FMD疫苗相当。来自5 BT和B5 BT组的血清在肽特异性ELISA中也显示出高的表位特异性抗体滴度，表明所有五个表位都暴露于用于抗体反应的B细胞受体。因此，本研究所设计的多表位重组蛋白有可能作为口蹄疫病毒流行变异株的替代疫苗。
Concerns regarding the safety of inactivated foot-and-mouth disease (FMD) vaccine have been raised since it is produced from cultured live FMD virus (FMDV). To overcome this issue, recombinant protein has been studied as an alternative vaccine. We designed a chimerical multi-epitope recombinant protein (5BT), which is comprised of tandem repeats of five B cell epitopes (residue of VP1 136–162) derived from different FMDV variants and one T-cell epitope (residue of 3A 21–35). To increase solubility and stability of 5BT, it was conjugated with BmpB, the membrane protein B of Brachyspira hyodysenteriae (B5BT). Our results indicated that 5BT was susceptible to degradation by host protease and produced with substantial fraction of inclusion body. The stability and solubility of 5BT was greatly increased by conjugating to BmpB. FMDV specific antibodies were observed in the serum of mice immunized with 5BT and B5BT comparable to inactivated FMD vaccine. Sera from 5BT and B5BT groups also exhibited high epitope-specific antibody titers in peptide specific ELISA, indicating that all five epitopes are exposed to the B cell receptor for the antibody reaction. Thus the multi-epitope recombinant protein designed in this study may be a potential candidate as an alternative vaccine against FMDV epidemic variants.