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含壳聚糖的蛋白酶体α1型亚基:传统佐剂的一种有前景的替代品。

Proteasome Subunit Alpha Type 1 with Chitosan: A Promising Alternative to Traditional Adjuvant.

作者信息

Yu Zhengqing, Ding Wenxi, Aleem Muhammad Tahir, Su Junzhi, Liu Junlong, Luo Jianxun, Yan Ruofeng, Xu Lixin, Song Xiaokai, Li Xiangrui

机构信息

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210000, China.

State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China.

出版信息

Pharmaceutics. 2021 May 19;13(5):752. doi: 10.3390/pharmaceutics13050752.

Abstract

As an important zoonotic protozoan, () has spread around the world, leading to infections in one-third of the population. There is still no effective vaccine or medicine against , and recombinant antigens entrapped within nanospheres have benefits over traditional vaccines. In the present study, we first expressed and purified proteasome subunit alpha type 1 (TgPSA1), then encapsulated the recombinant TgPSA1 (rTgPSA1) in chitosan nanospheres (CS nanospheres, rTgPSA1/CS nanospheres) and incomplete Freund's adjuvant (IFA, rTgPSA1/IFA emulsion). Antigens entrapped in CS nanospheres reached an encapsulation efficiency of 67.39%, and rTgPSA1/CS nanospheres showed a more stable release profile compared to rTgPSA1/IFA emulsion in vitro. In vivo, Th1-biased cellular and humoral immune responses were induced in mice and chickens immunized with rTgPSA1/CS nanospheres and rTgPSA1/IFA emulsion, accompanied by promoted production of antibodies, IFN-γ, IL-4, and IL-17, and modulated production of IL-10. Immunization with rTgPSA1/CS nanospheres and rTgPSA1/IFA emulsion conferred significant protection, with prolonged survival time in mice and significantly decreased parasite burden in chickens. Furthermore, our results also indicate that rTgPSA1/CS nanospheres could be used as a substitute for rTgPSA1/IFA emulsion, with the optimal administration route being intramuscular in mass vaccination. Collectively, the results of this study indicate that rTgPSA1/CS nanospheres represent a promising vaccine to protect animals against acute toxoplasmosis.

摘要

作为一种重要的人畜共患原生动物,()已在全球传播,导致三分之一的人口感染。目前仍没有针对()的有效疫苗或药物,而包裹在纳米球内的重组抗原有优于传统疫苗的优势。在本研究中,我们首先表达并纯化了蛋白酶体亚基α1型(TgPSA1),然后将重组TgPSA1(rTgPSA1)包裹在壳聚糖纳米球(CS纳米球,rTgPSA1/CS纳米球)和不完全弗氏佐剂(IFA,rTgPSA1/IFA乳剂)中。包裹在CS纳米球中的抗原包封率达到67.39%,与rTgPSA1/IFA乳剂相比,rTgPSA1/CS纳米球在体外显示出更稳定的释放曲线。在体内,用rTgPSA1/CS纳米球和rTgPSA1/IFA乳剂免疫的小鼠和鸡诱导了以Th1为主的细胞和体液免疫反应,伴随着抗体、IFN-γ、IL-4和IL-17的产生增加,以及IL-10的产生受到调节。用rTgPSA1/CS纳米球和rTgPSA1/IFA乳剂免疫可提供显著的保护,使小鼠存活时间延长,鸡体内的寄生虫负荷显著降低。此外,我们的结果还表明,rTgPSA1/CS纳米球可作为rTgPSA1/IFA乳剂的替代品,在大规模疫苗接种中最佳给药途径为肌肉注射。总体而言,本研究结果表明,rTgPSA1/CS纳米球是一种有前景的疫苗,可保护动物免受急性弓形虫病感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5c3/8161231/b0409465263f/pharmaceutics-13-00752-g001.jpg

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