The Pirbright Institute, Ash Road, Woking GU24 0NF, UK.
Bill & Melinda Gates Foundation, 500 5th Ave. N, Seattle, WA 98109, USA.
Viruses. 2022 Mar 16;14(3):621. doi: 10.3390/v14030621.
Foot-and-mouth disease (FMD) is endemic in large parts of sub-Saharan Africa, Asia and South America, where outbreaks in cloven-hooved livestock threaten food security and have severe economic impacts. Vaccination in endemic regions remains the most effective control strategy. Current FMD vaccines are produced from chemically inactivated foot-and-mouth disease virus (FMDV) grown in suspension cultures of baby hamster kidney 21 cells (BHK-21). Strain diversity means vaccines produced from one subtype may not fully protect against circulating disparate subtypes, necessitating the development of new vaccine strains that "antigenically match". However, some viruses have proven difficult to adapt to cell culture, slowing the manufacturing process, reducing vaccine yield and limiting the availability of effective vaccines, as well as potentiating the selection of undesired antigenic changes. To circumvent the need to cell culture adapt FMDV, we have used a systematic approach to develop recombinant suspension BHK-21 that stably express the key FMDV receptor integrin αvβ6. We show that αvβ6 expression is retained at consistently high levels as a mixed cell population and as a clonal cell line. Following exposure to field strains of FMDV, these recombinant BHK-21 facilitated higher virus yields compared to both parental and control BHK-21, whilst demonstrating comparable growth kinetics. The presented data supports the application of these recombinant αvβ6-expressing BHK-21 in future FMD vaccine production.
口蹄疫(FMD)在撒哈拉以南非洲、亚洲和南美洲的大片地区流行,偶蹄类牲畜的爆发威胁着粮食安全,并造成严重的经济影响。在流行地区接种疫苗仍然是最有效的控制策略。目前的口蹄疫疫苗是由在仓鼠肾 21 细胞(BHK-21)悬浮培养物中生长的化学灭活的口蹄疫病毒(FMDV)制成的。由于株系多样性,由一种亚型生产的疫苗可能无法完全预防循环的不同亚型,因此需要开发“抗原匹配”的新疫苗株。然而,一些病毒难以适应细胞培养,这会减缓制造过程,降低疫苗产量,限制有效疫苗的供应,并增加不期望的抗原变化的选择。为了避免对口蹄疫病毒进行细胞培养适应的需要,我们采用了一种系统的方法来开发稳定表达关键口蹄疫病毒受体整合素αvβ6 的重组悬浮 BHK-21。我们表明,αvβ6 的表达作为混合细胞群体和克隆细胞系保持在始终较高的水平。在暴露于田间口蹄疫病毒株后,与亲本和对照 BHK-21 相比,这些重组 BHK-21 提高了病毒产量,同时表现出相似的生长动力学。所提供的数据支持将这些表达αvβ6 的重组 BHK-21 应用于未来的口蹄疫疫苗生产。