Plum Island Animal Disease Center, U.S. Department of Homeland Security Science and Technology Directorate, New York, NY 11944, USA.
Plum Island Animal Disease Center, Leidos, New York, NY 11944, USA.
Viruses. 2022 May 7;14(5):989. doi: 10.3390/v14050989.
RNA viruses, such as foot-and-mouth disease virus (FMDV), have error-prone replication resulting in the continuous emergence of new viral strains capable of evading current vaccine coverage. Vaccine formulations must be regularly updated, which is both costly and technically challenging for many vaccine platforms. In this report, we describe a plasmid-based virus-like particle (VLP) production platform utilizing transiently transfected mammalian cell cultures that combines both the rapid response adaptability of nucleic-acid-based vaccines with the ability to produce intact capsid epitopes required for immunity. Formulated vaccines which employed this platform conferred complete protection from clinical foot-and-mouth disease in both swine and cattle. This novel platform can be quickly adapted to new viral strains and serotypes through targeted exchanges of only the FMDV capsid polypeptide nucleic acid sequences, from which processed structural capsid proteins are derived. This platform obviates the need for high biocontainment manufacturing facilities to produce inactivated whole-virus vaccines from infected mammalian cell cultures, which requires upstream expansion and downstream concentration of large quantities of live virulent viruses.
RNA 病毒，如口蹄疫病毒 (FMDV)，其复制过程易错，导致新的病毒株不断出现，能够逃避当前疫苗的覆盖范围。疫苗配方必须定期更新，这对于许多疫苗平台来说既昂贵又具有技术挑战性。在本报告中，我们描述了一种基于质粒的病毒样颗粒 (VLP) 生产平台，利用瞬时转染的哺乳动物细胞培养物，将核酸疫苗的快速响应适应性与产生完整衣壳表位的能力相结合，这些表位是免疫所必需的。采用该平台配制的疫苗可在猪和牛中完全预防临床口蹄疫。通过仅交换 FMDV 衣壳多肽核酸序列，该新型平台可以快速适应新的病毒株和血清型，这些序列衍生出加工后的结构衣壳蛋白。该平台无需使用高生物安全设施，即可从受感染的哺乳动物细胞培养物中生产灭活全病毒疫苗，这需要上游大量活毒病毒的扩增和下游大量活毒病毒的浓缩。
