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Thermostabilization of viruses via complex coacervation

机译：通过复杂的凝聚来热稳定病毒

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Widespread vaccine coverage for viral diseases could save the lives of millions of people each year. For viral vaccines to be effective, they must be transported and stored in a narrow temperature range of 2-8°C. If temperatures are not maintained, the vaccine may lose its potency and would no longer be effective in fighting disease; this is called the cold storage problem. Finding a way to thermally stabilize a virus and end the need to transport and store vaccines at refrigeration temperatures will increase access to life-saving vaccines. We explore the use of polymer-rich complex coacervates to stabilize viruses. We have developed a method of encapsulating virus particles in liquid complex coacervates that relies on the electrostatic interaction of viruses with polypeptides. In particular, we tested the incorporation of two model viruses; a non-enveloped porcine parvovirus (PPV) and an enveloped bovine viral diarrhea virus (BVDV) into coacervates formed from poly(lysine) and poly(glutamate). We identified optimal conditions (i.e., the relative amount of the two polypeptides) for virus encapsulation, and trends in this composition matched differences in the isoelectric point of the two viruses. Furthermore, we were able to achieve a ～10~3-10~4-fold concentration of virus into the coacervate phase, such that the level of virus remaining in the bulk solution approached our limit of detection. Lastly, we demonstrated a significant enhancement of the stability of non-enveloped PPV during an accelerated aging study at 60°C over the course of a week. Our results suggest the potential for using coacervation to aid in the purification and formulation of both enveloped and non-enveloped viruses, and that coacervate-based formulations could help limit the need for cold storage throughout the transportation and storage of vaccines based on non-enveloped viruses.
机译：病毒疾病的广泛疫苗覆盖可能每年可以挽救数百万人的生活。对于有效的病毒疫苗，必须将它们输送并储存在2-8℃的窄温度范围内。如果不维持温度，疫苗可能会失去其效力，并且不再有效地对抗疾病;这被称为冷库问题。寻找一种方法来热稳定病毒，结束需要在制冷温度下运输和储存疫苗的需要将增加对救生疫苗的进入。我们探讨了使用富含聚合物的复合物凝聚法以稳定病毒。我们开发了一种封装在液体复合凝聚中的病毒颗粒的方法，其依赖于多肽病毒的静电相互作用。特别是，我们测试了两种模型病毒的掺入;一种非包裹的猪细胞病毒（PPV）和包裹的牛病毒腹泻病毒（BVDV）成凝聚物，由聚（赖氨酸）和聚（谷氨酸）形成。我们鉴定了病毒封装的最佳条件（即，两种多肽的相对量），并且该组合物的趋势匹配两种病毒的等电点的差异。此外，我们能够达到〜10〜3-10〜4倍的病毒进入凝聚阶段，使得散装溶液中残留的病毒水平接近我们的检测极限。最后，我们证明在每周60℃的加速老化研究期间，在加速老化研究期间对非包裹的PPV的稳定性提高了显着提高。我们的研究结果表明，使用凝聚方法可以帮助纯化和配制包膜和非包膜病毒，以及基于凝聚层的制剂可以帮助限制在整个运输和储存疫苗整个疫苗的情况下的需要病毒。

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  • 来源
    《Biomaterials Science》 |2020年第24期|共11页
  • 作者

    Xue Mi; Whitney C. Blocher McTigue; Pratik U. Joshi; Mallory K. Bunker; Caryn L. Heldt; Sarah L. Perry;

  • 作者单位

    Department of Chemical Engineering Michigan Technological University USA;

    Department of Chemical Engineering University of Massachusetts Amherst USA;

    Department of Chemical Engineering Michigan Technological University USA;

    Department of Chemical Engineering Michigan Technological University USA;

    Department of Chemical Engineering Michigan Technological University USA;

    Department of Chemical Engineering University of Massachusetts Amherst USA;

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  • 正文语种 eng
  • 中图分类 计量学;
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