Hewitt Cory R, Wixon Nicholas J, Gallegos Arthur, Zhou You, Huber Victor C, Killian M Scott
Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA.
Microscopy Core Research Facility, Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
Vaccines (Basel). 2025 Jan 16;13(1):79. doi: 10.3390/vaccines13010079.
: Zika virus (ZIKV) infection is associated with life-threatening diseases in humans. To date, there are no available FDA-approved therapies or vaccines for the specific treatment or prevention of ZIKV infection. Variation in the ZIKV envelope protein (Env), along with its complex quaternary structure, presents challenges to synthetic approaches for developing an effective vaccine and broadly neutralizing antibodies (bnAbs). We hypothesized that beta-cyclodextrin (BCD) could be used to uniquely inactivate infectious ZIKV without disruption of Env. : ZIKV was propagated in Vero cells and admixed with BCD. The BCD-treated ZIKV was evaluated for infectivity using immunofluorescence and quantitative RT-PCR (qRT-PCR) assays, for immunoreactivity in Western blots, structural integrity by electron microscopy, and immunogenicity in mice. : Here, we show that 200 mM BCD-treated ZIKV is non-infectious in cell culture, remains immunoreactive with an Env-specific antibody, retains its virion shape and size, and elicits the production of immunogen-specific antibodies in immunized mice. : These results indicate that BCD can be used to safely inactivate ZIKV, and they provide insights for vaccine and antibody development.
寨卡病毒（ZIKV）感染与人类危及生命的疾病相关。迄今为止，尚无美国食品药品监督管理局（FDA）批准的用于特异性治疗或预防ZIKV感染的疗法或疫苗。ZIKV包膜蛋白（Env）的变异及其复杂的四级结构，给开发有效疫苗和广谱中和抗体（bnAbs）的合成方法带来了挑战。我们推测β-环糊精（BCD）可用于特异性灭活感染性ZIKV，而不破坏Env。ZIKV在Vero细胞中繁殖，并与BCD混合。使用免疫荧光和定量逆转录聚合酶链反应（qRT-PCR）测定法评估经BCD处理的ZIKV的感染性，通过蛋白质印迹法评估其免疫反应性，通过电子显微镜评估其结构完整性，并在小鼠中评估其免疫原性。在此，我们表明200 mM BCD处理的ZIKV在细胞培养中无感染性，与Env特异性抗体保持免疫反应性，保留其病毒体形状和大小，并在免疫小鼠中引发免疫原特异性抗体的产生。这些结果表明BCD可用于安全地灭活ZIKV，并为疫苗和抗体开发提供了思路。
