Recombinant Adenoviruses Displaying Matrix 2 Ectodomain Epitopes on Their Fiber Proteins as Universal Influenza Vaccines
Recombinant Adenoviruses Displaying Matrix 2 Ectodomain Epitopes on Their Fiber Proteins as Universal Influenza Vaccines
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在其纤维蛋白上展示基质 2 胞外域表位 (M2e) 的重组腺病毒作为通用流感疫苗
DOI：
10.1128/jvi.02462-16
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发表时间：
2017-04-01
影响因子：
5.4
通讯作者：
Zhou, Dongming
中科院分区：
文献类型：
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作者：
Tang, Xinying;Yang, Yong;Zhou, Dongming
流感是一种人畜共患疾病，对公共卫生和全球经济构成严重威胁。再次出现的流感大流行突出了对通用流感疫苗的需求。我们开发了一种新的病毒平台，使用基质2蛋白（M2 e）的胞外结构域IV，AdC 68-F3 M2 e，通过将三个保守的M2 e表位引入黑猩猩腺病毒（AdV）纤维蛋白的HI环。M2 e表位在AdV病毒粒子表面上充分表达，而不影响纤维三聚化。此外，一种重组腺病毒AdC 68 F3 M2 e（H1-H5-H7）在两次连续接种后在BALB/c小鼠中诱导了稳健的M2 e特异性抗体应答，并赋予针对同源和异源流感病毒（IV）攻击的有效保护。我们发现，在纤维中使用具有串联M2 e表位的AdV是预防流感的潜在策略。流感流行和大流行严重威胁公共卫生。近年来，通用流感疫苗越来越引起人们的兴趣。在这里，我们描述了一种新的策略，将三重M2 E表位到黑猩猩腺病毒68的纤维蛋白。我们通过一步等温组装优化了外源基因插入AdC 68结构蛋白的过程，并证明了这种225 bp的HI环插入可以很好地耐受。此外，两个剂量的无絮凝剂的纤维修饰的AdC 68可以在小鼠中赋予针对同源和异源流感病毒感染的足够保护。我们的研究结果表明，AdC 68-F3 M2 e可以作为一种新的通用流感疫苗。
Influenza is a zoonotic disease that poses severe threats to public health and the global economy. Reemerging influenza pandemics highlight the demand for universal influenza vaccines. We developed a novel virus platform using extracellular domain IV of the matrix 2 protein (M2e), AdC68-F3M2e, by introducing three conserved M2e epitopes into the HI loop of the chimpanzee adenovirus (AdV) fiber protein. The M2e epitopes were expressed sufficiently on the AdV virion surface without affecting fiber trimerization. Additionally, one recombinant adenovirus, AdC68F3M2e(H1-H5-H7), induced robust M2e-specific antibody responses in BALB/c mice after two sequential vaccinations and conferred efficient protection against homologous and heterologous influenza virus (IV) challenges. We found that the use of AdV with tandem M2e epitopes in fiber is a potential strategy for influenza prevention. IMPORTANCE Influenza epidemics and pandemics severely threaten public health. Universal influenza vaccines have increasingly attracted interest in recent years. Here, we describe a new strategy that incorporates triple M2e epitopes into the fiber protein of chimpanzee adenovirus 68. We optimized the process of inserting foreign genes into the AdC68 structural protein by one-step isothermal assembly and demonstrated that this 225-bp HI loop insertion could be well tolerated. Furthermore, two doses of adjuvant-free fiber-modified AdC68 could confer sufficient protection against homologous and heterologous influenza virus infections in mice. Our results show that AdC68-F3M2e could be pursued as a novel universal influenza vaccine.