Petrovsky Nikolai
Flinders Medical Centre, Flinders University, Bedford Park SA 4052, Australia.
Vaccine. 2006 Apr 12;24 Suppl 2(Suppl 2):S2-26-9. doi: 10.1016/j.vaccine.2005.01.107.
Pure soluble, recombinant and synthetic antigens, despite their better tolerability, are unfortunately often much less immunogenic than live or killed whole organism vaccines. Thus, the move towards the development of safer subunit vaccines has created a major need for more potent adjuvants. In particular, there is an urgent need for adjuvants capable of boosting cellular (Th1) immunity but without unacceptable toxicity. The adjuvant activity of aluminium compounds (aluminium phosphate or hydroxide) was first described by Glenny and colleagues in 1926. Surprisingly, despite the description of over one hundred adjuvants in the scientific literature, alum remains the only adjuvant approved for human use in the USA. Unfortunately, alum has no effect on cellular immunity and is faced with increasing concerns regarding potential for cumulative aluminium toxicity. Why then has alum not been replaced in human vaccines? Despite the enormous number of candidates, potency has invariably been associated with increased toxicity, and this more than anything else has precluded their use, particularly in prophylactic vaccines where safety issues are paramount. Hence, there is a major unmet need for a safe efficacious adjuvant capable of boosting cellular plus humoral immunity. The extensive data on inulin-based adjuvants indicate that these are excellent candidates to replace alum as the adjuvant of choice for many vaccines. Particular advantages offered by inulin-based adjuvants is that they induce cellular in addition to humoral immunity and offer excellent safety, tolerability, ease of manufacture and formulation. Thus, adjuvants based on inulin have enormous potential for use in vaccines against both pathogens and cancer.
纯可溶性、重组和合成抗原，尽管其耐受性较好，但不幸的是，它们的免疫原性往往比活的或灭活的全生物体疫苗低得多。因此，向更安全的亚单位疫苗发展的趋势产生了对更强效佐剂的重大需求。特别是，迫切需要能够增强细胞（Th1）免疫但又无不可接受毒性的佐剂。铝化合物（磷酸铝或氢氧化铝）的佐剂活性最早于1926年由格伦尼及其同事描述。令人惊讶的是，尽管科学文献中描述了一百多种佐剂，但明矾仍然是美国唯一被批准用于人类的佐剂。不幸的是，明矾对细胞免疫没有作用，并且人们对其潜在的累积铝毒性越来越担忧。那么为什么明矾在人类疫苗中没有被取代呢？尽管有大量的候选物，但效力总是与毒性增加相关，而这比其他任何因素都更阻碍了它们的使用，特别是在安全问题至关重要的预防性疫苗中。因此，迫切需要一种能够增强细胞免疫和体液免疫的安全有效的佐剂。关于基于菊粉的佐剂的大量数据表明，它们是取代明矾作为许多疫苗首选佐剂的优秀候选物。基于菊粉的佐剂具有的特别优势在于，它们除了能诱导体液免疫外，还能诱导细胞免疫，并且具有出色的安全性、耐受性、易于制造和配方。因此，基于菊粉的佐剂在针对病原体和癌症的疫苗中具有巨大的应用潜力。
