van Diepen Michiel, Chapman Rosamund, Douglass Nicola, Whittle Leah, Chineka Nicole, Galant Shireen, Cotchobos Christian, Suzuki Akiko, Williamson Anna-Lise
Department of Pathology, Division of Medical Virology, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa.
Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town 7925, South Africa.
Vaccines (Basel). 2021 Oct 4;9(10):1131. doi: 10.3390/vaccines9101131.
Attenuated vaccine strains of lumpy skin disease virus (LSDV) have become increasingly popular as recombinant vaccine vectors, to target both LSDV, as well as other pathogens, including human infectious agents. Historically, these vaccine strains and recombinants were generated in primary (lamb) testis (LT) cells, Madin-Darby bovine kidney (MDBK) cells or in eggs. Growth in eggs is a laborious process, the use of primary cells has the potential to introduce pathogens and MDBK cells are known to harbor bovine viral diarrhea virus (BVDV). In this study, data is presented to show the growth of an attenuated LSDV strain in baby hamster kidney (BHK-21) cells. Subsequently, a recombinant LSDV vaccine was generated in BHK-21 cells. Partial growth was also observed in rabbit kidney cells (RK13), but only when the vaccinia virus host range gene K1L was expressed. Despite the limited growth, the expression of K1L was enough to serve as a positive selection marker for the generation of recombinant LSDV vaccines in RK13 cells. The simplification of generating (recombinant) LSDV vaccines shown here should increase the interest for this platform for future livestock vaccine development and, with BHK-21 cells approved for current good manufacturing practice, this can be expanded to human vaccines as well.
结节性皮肤病病毒(LSDV)的减毒疫苗株作为重组疫苗载体越来越受欢迎,可用于针对LSDV以及其他病原体,包括人类感染因子。从历史上看,这些疫苗株和重组体是在原代(羔羊)睾丸(LT)细胞、马-达二氏牛肾(MDBK)细胞或鸡蛋中产生的。在鸡蛋中培养是一个费力的过程,使用原代细胞有可能引入病原体,并且已知MDBK细胞携带牛病毒性腹泻病毒(BVDV)。在本研究中,展示了数据以表明一种减毒LSDV株在幼仓鼠肾(BHK-21)细胞中的生长情况。随后,在BHK-21细胞中产生了一种重组LSDV疫苗。在兔肾细胞(RK13)中也观察到了部分生长,但仅在痘苗病毒宿主范围基因K1L表达时。尽管生长有限,但K1L的表达足以作为在RK13细胞中产生重组LSDV疫苗的阳性选择标记。此处展示的(重组)LSDV疫苗生产的简化应会增加该平台在未来家畜疫苗开发方面的吸引力,并且鉴于BHK-21细胞已获现行良好生产规范批准,这也可扩展至人类疫苗。