Development of a broadly protective modified-live virus vaccine candidate against porcine reproductive and respiratory syndrome virus.
Development of a broadly protective modified-live virus vaccine candidate against porcine reproductive and respiratory syndrome virus.
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DOI：
10.1016/j.vaccine.2017.11.028
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发表时间：
2018-01
期刊：
影响因子：
5.5
通讯作者：
Haiyan Sun;Aspen M. Workman;F. Osorio;D. Steffen;H. Vu
中科院分区：
文献类型：
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作者：
Haiyan Sun;Aspen M. Workman;F. Osorio;D. Steffen;H. Vu
改良活病毒疫苗（MLV）被广泛用于保护猪免受猪繁殖与呼吸综合征病毒（PRRSV）的侵害。然而，目前的MLV疫苗不能提供足够水平的异源保护，这可能是由于在田间传播的PRRSV分离株的大量遗传多样性。为了克服这种遗传变异的挑战，我们最近产生了一种合成的PRRSV毒株，其中含有PRRSV-2的共有基因组序列。我们证明了我们的合成PRRSV毒株赋予前所未有的异源保护水平。然而，第1代的合成PRRSV毒株（下文称为CON-P1）是高毒性的，因此不适合用作猪的疫苗。在本研究中，我们通过在MARC-145细胞（一种非天然宿主细胞系）中连续传代病毒来减毒CON-P1。使用幼猪模型，我们证明了第90代和第122代的合成病毒（分别命名为CON-P90和CON-P122）完全减毒，如血清和组织中病毒载量显著降低以及感染猪中不存在肺部病变所证明的。最重要的是，CON-P90赋予与其亲本菌株CON-P1相似的异源保护水平。综上所述，结果表明，CON-P90是用于配制具有改善的异源保护水平的下一代PRRSV MLV疫苗的优秀候选物。
Modified-live virus (MLV) vaccines are widely used to protect pigs against porcine reproductive and respiratory syndrome virus (PRRSV). However, current MLV vaccines do not confer adequate levels of heterologous protection, presumably due to the substantial genetic diversity of PRRSV isolates circulating in the field. To overcome this genetic variation challenge, we recently generated a synthetic PRRSV strain containing a consensus genomic sequence of PRRSV-2. We demonstrated that our synthetic PRRSV strain confers unprecedented levels of heterologous protection. However, the synthetic PRRSV strain at passage 1 (hereafter designated CON-P1) is highly virulent and therefore, is not suitable to be used as a vaccine in pigs. In the present study, we attenuated CON-P1 by continuously passaging the virus in MARC-145 cells, a non-natural host cell line. Using a young pig model, we demonstrated that the synthetic virus at passages 90 and 122 (designated as CON-P90 and CON-P122, respectively) were fully attenuated, as evidenced by the significantly reduced viral loads in serum and tissues and the absence of lung lesion in the infected pigs. Most importantly, CON-P90 confers similar levels of heterologous protection as its parental strain CON-P1. Taken together, the results indicate that CON-P90 is an excellent candidate for the formulation of next generation of PRRSV MLV vaccines with improved levels of heterologous protection.