Inulin‐derived adjuvants efficiently promote both Th1 and Th2 immune responses
Inulin‐derived adjuvants efficiently promote both Th1 and Th2 immune responses
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DOI：
10.1111/j.1440-1711.2004.01290.x
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发表时间：
2004-12
影响因子：
4
通讯作者：
Diego G. Silva;P. Cooper;N. Petrovsky
中科院分区：
文献类型：
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作者：
Diego G. Silva;P. Cooper;N. Petrovsky
最近对新的和改进的疫苗佐剂的兴趣重新抬头。这种兴趣是由于需要新的疫苗来对抗有问题的病原体，如SARS和艾滋病毒，并对抗潜在的生物恐怖袭击。疫苗开发中的主要瓶颈是纯化的亚单位或重组蛋白的低免疫原性，从而产生对具有高效力的安全人佐剂的需要。寻找理想佐剂的一个主要问题是促进细胞介导（Th 1）免疫的佐剂（例如弗氏完全佐剂）通常具有不可接受的局部或全身毒性，这使得它们无法用于人类疫苗。需要一种能够刺激细胞介导和体液免疫的安全无毒佐剂。菊粉衍生的佐剂主要通过其激活替代补体途径的能力来刺激先天免疫系统，已证明其具有诱导细胞和体液免疫的能力。由于其优异的耐受性、长保质期、低成本和易于制造，它们在广泛的预防性和治疗性疫苗中具有巨大的应用潜力。基于在广泛物种中成功的动物研究，人体试验即将开始，以验证菊糖佐剂在预防B型肝炎、疟疾和其他病原体的疫苗中的使用。如果这些试验成功，那么菊粉衍生的佐剂有一天可能会取代明矾作为大多数人类预防性疫苗的首选佐剂。
There has been a recent resurgence of interest into new and improved vaccine adjuvants. This interest has been stimulated by the need for new vaccines to combat problematic pathogens such as SARS and HIV, and to counter potential bioterrorist attacks. A major bottleneck in vaccine development is the low immunogenicity of purified subunit or recombinant proteins, creating the need for safe human adjuvants with high potency. A major problem in the search for the ideal adjuvant is that adjuvants that promote cell‐mediated (Th1) immunity (e.g. Freund's complete adjuvant) generally have unacceptable local or systemic toxicity that precludes their use in human vaccines. There is a need for a safe, non‐toxic adjuvant that is able to stimulate both cell‐mediated and humoral immunity. Inulin‐derived adjuvants that principally stimulate the innate immune system through their ability to activate the alternative complement pathway have proven ability to induce both cellular and humoral immunity. With their excellent tolerability, long shelf‐life, low cost and easy manufacture, they offer great potential for use in a broad range of prophylactic and therapeutic vaccines. Based on successful animal studies in a broad range of species, human trials are about to get underway to validate the use of inulin‐based adjuvants in prophylactic vaccines against hepatitis B, malaria and other pathogens. If such trials are successful, then it is possible that inulin‐derived adjuvants will one day replace alum as the adjuvant of choice in most human prophylactic vaccines.