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Characterization of the Biodistribution of a Silica Vesicle Nanovaccine Carrying a Rhipicephalus (Boophilus) microplus Protective Antigen With in vivo Live Animal Imaging
Frontiers in Bioengineering and Biotechnology ( IF 4.3 ) Pub Date : 2021-01-18 , DOI: 10.3389/fbioe.2020.606652
Karishma T. Mody , Bing Zhang , Xun Li , Nicholas L. Fletcher , Dewan T. Akhter , Sandy Jarrett , Jun Zhang , Chengzhong Yu , Kristofer J. Thurecht , Timothy J. Mahony , Neena Mitter

Development of veterinary subunit vaccines comes with a spectrum of challenges, such as the choice of adjuvant, antigen delivery vehicle, and optimization of dosing strategy. Over the years, our laboratory has largely focused on investigating silica vesicles (SVs) for developing effective veterinary vaccines for multiple targets. Rhipicephalus microplus (cattle tick) are known to have a high impact on cattle health and the livestock industry in the tropical and subtropical regions. Development of vaccine using Bm86 antigen against R. microplus has emerged as an attractive alternative to control ticks. In this study, we have investigated the biodistribution of SV in a live animal model, as well as further explored the SV ability for vaccine development. Rhodamine-labeled SV-140-C18 (Rho-SV-140-C18) vesicles were used to adsorb the Cy5-labeled R. microplus Bm86 antigen (Cy5-Bm86) to enable detection and characterization of the biodistribution of SV as well as antigen in vivo in a small animal model for up to 28 days using optical fluorescence imaging. We tracked the in vivo biodistribution of SVs and Bm86 antigen at different timepoints (days 3, 8, 13, and 28) in BALB/c mice. The biodistribution analysis by live imaging as well as by measuring the fluorescent intensity of harvested organs over the duration of the experiment (28 days) showed greater accumulation of SVs at the site of injection. The Bm86 antigen biodistribution was traced in lymph nodes, kidney, and liver, contributing to our understanding how this delivery platform successfully elicits antibody responses in the groups administered antigen in combination with SV. Selected tissues (skin, lymph nodes, spleen, kidney, liver, and lungs) were examined for any cellular abnormalities by histological analysis. No adverse effect or any other abnormalities were observed in the tissues.

中文翻译:

通过体内活体动物成像表征携带 Rhipicephalus (Boophilus) microplus 保护性抗原的二氧化硅囊泡纳米疫苗的生物分布

兽用亚单位疫苗的开发面临一系列挑战,例如佐剂的选择、抗原递送载体和剂量策略的优化。多年来,我们的实验室主要专注于研究二氧化硅囊泡 (SV),以开发针对多个目标的有效兽用疫苗。Rhipicephalus microplus(牛蜱)已知对热带和亚热带地区的牛健康和畜牧业有很大影响。使用 Bm86 抗原开发针对 R. microplus 的疫苗已成为控制蜱的有吸引力的替代方案。在这项研究中,我们研究了 SV 在活体动物模型中的生物分布,并进一步探索了 SV 开发疫苗的能力。罗丹明标记的 SV-140-C18 (Rho-SV-140-C18) 囊泡用于吸附 Cy5 标记的 R。microplus Bm86 抗原 (Cy5-Bm86) 能够使用光学荧光成像在小动物模型中检测和表征 SV 的生物分布以及体内抗原长达 28 天。我们在 BALB/c 小鼠的不同时间点(第 3、8、13 和 28 天)跟踪了 SV 和 Bm86 抗原的体内生物分布。通过实时成像以及在实验期间(28 天)测量收获器官的荧光强度进行的生物分布分析表明,注射部位的 SV 积累更多。在淋巴结、肾脏和肝脏中追踪了​​ Bm86 抗原的生物分布,有助于我们了解该递送平台如何在与 SV 组合施用抗原的组中成功引发抗体反应。选定的组织(皮肤、淋巴结、脾脏、肾脏、肝脏、和肺)通过组织学分析检查任何细胞异常。在组织中没有观察到副作用或任何其他异常。
更新日期:2021-01-18
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