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用于疫苗开发的新型佐剂和递送载体:前行之路。

Novel adjuvants & delivery vehicles for vaccines development: a road ahead.

作者信息

Mohan Teena, Verma Priyanka, Rao D Nageswara

机构信息

Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.

出版信息

Indian J Med Res. 2013 Nov;138(5):779-95.

Abstract

The pure recombinant and synthetic antigens used in modern day vaccines are generally less immunogenic than older style live/attenuated and killed whole organism vaccines. One can improve the quality of vaccine production by incorporating immunomodulators or adjuvants with modified delivery vehicles viz. liposomes, immune stimulating complexes (ISCOMs), micro/nanospheres apart from alum, being used as gold standard. Adjuvants are used to augment the effect of a vaccine by stimulating the immune system to respond to the vaccine, more vigorously, and thus providing increased immunity to a particular disease. Adjuvants accomplish this task by mimicking specific sets of evolutionary conserved molecules which include lipopolysaccharides (LPS), components of bacterial cell wall, endocytosed nucleic acids such as dsRNA, ssDNA and unmethylated CpG dinucleotide containing DNA. This review provides information on various vaccine adjuvants and delivery vehicles being developed to date. From literature, it seems that the humoral immune responses have been observed for most adjuvants and delivery platforms while viral-vector, ISCOMs and Montanides have shown cytotoxic T-cell response in the clinical trials. MF59 and MPL® have elicited Th1 responses, and virus-like particles (VLPs), non-degradable nanoparticle and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clinical success reported for intranasal delivery of viral-vectors and proteosomes and oral delivery of VLP vaccines.

摘要

现代疫苗中使用的纯重组抗原和合成抗原,其免疫原性通常低于老式的活/减毒全病原体疫苗和灭活全病原体疫苗。通过将免疫调节剂或佐剂与改良的递送载体(即脂质体、免疫刺激复合物(ISCOM)、微/纳米球)相结合,可以提高疫苗生产的质量,除了明矾之外,明矾被用作金标准。佐剂用于通过刺激免疫系统对疫苗做出更强烈的反应来增强疫苗的效果,从而提高对特定疾病的免疫力。佐剂通过模拟特定的一组进化保守分子来完成这项任务,这些分子包括脂多糖(LPS)、细菌细胞壁成分、内吞的核酸,如双链RNA、单链DNA和含有未甲基化CpG二核苷酸的DNA。这篇综述提供了迄今为止正在研发的各种疫苗佐剂和递送载体的信息。从文献来看,大多数佐剂和递送平台都观察到了体液免疫反应,而病毒载体、ISCOM和Montanide在临床试验中显示出细胞毒性T细胞反应。MF59和MPL®引发了Th1反应,病毒样颗粒(VLP)、不可降解的纳米颗粒和脂质体也产生了细胞免疫。这些疫苗成分也已针对替代给药途径进行了评估,病毒载体和蛋白酶体的鼻内给药以及VLP疫苗的口服给药均有临床成功的报道。

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