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使用pH敏感且具有粘膜粘附性的硫醇化邻苯二甲酸醋酸纤维素微粒进行口蹄疫病毒疫苗的口服免疫

Oral Immunization of FMDV Vaccine Using pH-Sensitive and Mucoadhesive Thiolated Cellulose Acetate Phthalate Microparticles.

作者信息

Lee Ho-Bin, Yoon So-Yeon, Singh Bijay, Oh Seo-Ho, Cui Lianhua, Yan Changguo, Kang Sang-Kee, Choi Yun-Jaie, Cho Chong-Su

机构信息

1Department of Agricultural Biotechnology, Seoul National University, 1 Gwanak-ro, Gwanak-gu Seoul, 08826 Republic of Korea.

2Research Institute for Agriculture and Life Science, Seoul National University, 1 Gwanak-ro, Gwanak-gu Seoul, 08826 Republic of Korea.

出版信息

Tissue Eng Regen Med. 2017 Oct 17;15(1):1-11. doi: 10.1007/s13770-017-0082-x. eCollection 2018 Feb.

Abstract

Several barriers such as gastric pH, enzymatic degradation and rapid transit should be overcome to orally deliver antigens for taking up by epithelial microfold cells in Peyer's patches of small intestine. To solve the above mentioned problems, we designed pH-sensitive and mucoadhesive polymeric microparticles (MPs) prepared by double emulsion technique using cellulose acetate phthalate (CAP) to enhance immune response of foot-and-mouth disease (FMD) virus (FMDV) subunit vaccine. Thiolation of CAP improved mucoadhesive property of CAP to prolong the MPs transit time through the gastrointestinal tract. Thiolated CAP (T-CAP) also slowed down antigen release in acidic pH of stomach but released more antigens in neutral pH of small intestine due to the pH-sensitivity of the T-CAP. Oral immunization of a chimerical multi-epitope recombinant protein as the FMD subunit vaccine via T-CAP MPs effectively delivered the vaccine to Peyer's patches eliciting mucosal IgA response. It will make a step forward into a promising oral subunit vaccine development in livestock industry.

摘要

为了使抗原能够通过口服递送至小肠派尔集合淋巴结中的上皮微褶细胞,需要克服诸如胃内pH值、酶降解和快速转运等多种障碍。为了解决上述问题,我们设计了pH敏感且具有粘膜粘附性的聚合物微粒(MPs),其通过双乳液技术使用邻苯二甲酸醋酸纤维素(CAP)制备而成,用于增强口蹄疫(FMD)病毒(FMDV)亚单位疫苗的免疫反应。CAP的硫醇化改善了CAP的粘膜粘附性能,从而延长了MPs在胃肠道中的转运时间。硫醇化的CAP(T-CAP)在胃的酸性pH值环境中也减缓了抗原释放,但由于T-CAP的pH敏感性,在小肠的中性pH值环境中释放了更多抗原。通过T-CAP MPs口服免疫一种作为FMD亚单位疫苗的嵌合多表位重组蛋白,有效地将疫苗递送至派尔集合淋巴结,引发粘膜IgA反应。这将朝着家畜业中一种有前景的口服亚单位疫苗开发迈出一步。

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