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负载脂多糖亚基抗原的藻酸盐微粒用于肺炎克雷伯菌的黏膜疫苗接种

Alginate microparticles loaded with lipopolysaccharide subunit antigen for mucosal vaccination against Klebsiella pneumoniae.

作者信息

Jain R R, Mehta M R, Bannalikar A R, Menon M D

机构信息

Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai 400098, Maharashtra, India.

Department of Veterinary Microbiology, Bombay Veterinary College, Parel (E), Mumbai 400012, India.

出版信息

Biologicals. 2015 May;43(3):195-201. doi: 10.1016/j.biologicals.2015.02.001. Epub 2015 Feb 28.

DOI:10.1016/j.biologicals.2015.02.001
PMID:25737397
Abstract

Klebsiella pneumoniae (K. pneumoniae) is one of the commonest causes of nosocomial infections in human beings. Since K. pneumoniae infections are air borne type, controlling it by mucosal vaccination through nasal and pulmonary route could be a promising approach in order to simulate the natural infection. New vaccines such as subunit vaccines are safer than traditional vaccines, but they are less immunogenic. Therefore to enhance their immunogenicity, there is a need to develop potent and safe adjuvants and delivery systems. It has been established that micro-particles are one of the most potent adjuvants available for mucosal delivery of vaccines and they do so by improving uptake of encapsulated antigen by antigen presenting cells (APCs). Lipopolysaccharide (LPS), the antigenic fraction was extracted from K. pneumoniae by hot phenol extraction method. LPS loaded sodium alginate microparticles were prepared by emulsion ionic gelation method. Microparticles with particle size less than 5 μm were obtained. Loading efficiency of the LPS loaded microparticles ranged from 76 to 82 %. Comparative in vivo immunogenicity studies were carried for free LPS and encapsulated LPS, administered via intramuscular, intratracheal and intranasal routes in Swiss albino mice. The study revealed that LPS encapsulated microparticles exhibit greater efficacy when administered by intra-tracheal route as compared to free LPS vaccine.

摘要

肺炎克雷伯菌是人类医院感染最常见的病因之一。由于肺炎克雷伯菌感染是空气传播型,通过鼻腔和肺部途径进行黏膜疫苗接种来控制感染可能是一种有前景的方法,以模拟自然感染。诸如亚单位疫苗等新型疫苗比传统疫苗更安全,但免疫原性较低。因此,为了增强其免疫原性,需要开发高效且安全的佐剂和递送系统。已经确定,微粒是可用于疫苗黏膜递送的最有效的佐剂之一,它们通过改善抗原呈递细胞(APC)对包封抗原的摄取来实现这一点。通过热酚提取法从肺炎克雷伯菌中提取抗原性成分脂多糖(LPS)。采用乳液离子凝胶法制备了负载LPS的海藻酸钠微粒。获得了粒径小于5μm的微粒。负载LPS的微粒的负载效率在76%至82%之间。在瑞士白化小鼠中,对通过肌肉内、气管内和鼻内途径给药的游离LPS和包封LPS进行了体内免疫原性比较研究。研究表明,与游离LPS疫苗相比,经气管内途径给药时,LPS包封的微粒表现出更高的效力。

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