Peek Laura J, Middaugh C Russell, Berkland Cory
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66047 USA.
Adv Drug Deliv Rev. 2008 May 22;60(8):915-28. doi: 10.1016/j.addr.2007.05.017. Epub 2008 Feb 7.
With very few adjuvants currently being used in marketed human vaccines, a critical need exists for novel immunopotentiators and delivery vehicles capable of eliciting humoral, cellular and mucosal immunity. Such crucial vaccine components could facilitate the development of novel vaccines for viral and parasitic infections, such as hepatitis, HIV, malaria, cancer, etc. In this review, we discuss clinical trial results for various vaccine adjuvants and delivery vehicles being developed that are approximately nanoscale (<1000 nm) in size. Humoral immune responses have been observed for most adjuvants and delivery platforms while only viral vectors, ISCOMs and Montanide ISA 51 and 720 have shown cytotoxic T cell responses in the clinic. MF59 and MPL have elicited Th1 responses, and virus-like particles, non-degradable nanoparticles and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clinical successes reported for intranasal delivery of viral vectors and proteosomes and oral delivery of a VLP vaccine.
目前在市售人用疫苗中使用的佐剂极少,因此迫切需要能够引发体液免疫、细胞免疫和黏膜免疫的新型免疫增强剂和递送载体。这类关键的疫苗成分有助于开发针对病毒和寄生虫感染(如肝炎、HIV、疟疾、癌症等)的新型疫苗。在本综述中,我们讨论了正在研发的各种尺寸约为纳米级(<1000 nm)的疫苗佐剂和递送载体的临床试验结果。大多数佐剂和递送平台都观察到了体液免疫反应,而在临床上只有病毒载体、免疫刺激复合物以及Montanide ISA 51和720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、不可降解纳米颗粒和脂质体也产生了细胞免疫。这类疫苗成分还针对其他给药途径进行了评估,鼻内递送病毒载体和蛋白酶体以及口服VLP疫苗均报告了临床成功案例。