Mody Karishma T, Zhang Bing, Li Xun, Fletcher Nicholas L, Akhter Dewan T, Jarrett Sandy, Zhang Jun, Yu Chengzhong, Thurecht Kristofer J, Mahony Timothy J, Mitter Neena
Queensland Alliance for Agriculture and Food Innovation, The University of Queensland, Brisbane, QLD, Australia.
Animal Science, Queensland Department of Agriculture and Fisheries, St Lucia, QLD, Australia.
Front Bioeng Biotechnol. 2021 Jan 18;8:606652. doi: 10.3389/fbioe.2020.606652. eCollection 2020.
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. (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 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-C (Rho-SV-140-C) vesicles were used to adsorb the Cy5-labeled Bm86 antigen (Cy5-Bm86) to enable detection and characterization of the biodistribution of SV as well as antigen in a small animal model for up to 28 days using optical fluorescence imaging. We tracked the 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.
兽用亚单位疫苗的研发面临一系列挑战,例如佐剂的选择、抗原递送载体以及给药策略的优化。多年来,我们实验室主要致力于研究二氧化硅囊泡(SVs),以开发针对多种靶点的有效兽用疫苗。(牛蜱)已知对热带和亚热带地区的牛健康及畜牧业有重大影响。利用抗Bm86抗原开发疫苗已成为控制蜱虫的一种有吸引力的替代方法。在本研究中,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用于疫苗开发的能力。用罗丹明标记的SV - 140 - C(Rho - SV - 140 - C)囊泡吸附Cy5标记的Bm86抗原(Cy5 - Bm86),以便使用光学荧光成像在小动物模型中检测和表征SV以及抗原长达28天的生物分布。我们在不同时间点(第3天、第8天、第13天和第28天)追踪了BALB/c小鼠体内SVs和Bm86抗原的生物分布。通过活体成像以及在实验持续时间(28天)内测量收获器官的荧光强度进行的生物分布分析表明,SVs在注射部位有更多积累。在淋巴结、肾脏和肝脏中追踪到了Bm86抗原的生物分布,这有助于我们了解该递送平台如何在与SV联合给予抗原的组中成功引发抗体反应。通过组织学分析检查了选定的组织(皮肤、淋巴结、脾脏、肾脏、肝脏和肺)是否存在任何细胞异常。在这些组织中未观察到不良反应或任何其他异常。