Del Giudice G, Podda A, Rappuoli R
IRIS Research Center, Chiron SpA, Via Fiorentina 1, 53100, Siena, Italy.
Vaccine. 2001 Oct 15;20 Suppl 1:S38-41. doi: 10.1016/s0264-410x(01)00288-2.
Vaccines developed traditionally following empirical approaches have often limited problems of immunogenicity, probably due to the low level of purity of the active component(s) they contain. The application of new technologies to vaccine development is leading to the production of purer (e.g. recombinant) antigens which, however, tend to have a poorer immunogenicity as compared to vaccines of the previous generation. The search for new vaccine adjuvants involves issues related to their potential limits. Since the introduction of aluminium salts as vaccine adjuvants more than 70 years ago, only one adjuvant has been licensed for human use. The development of some of these new vaccine adjuvants has been hampered by their inacceptable reactogenicity. In addition, some adjuvants work strongly with some antigens but not with others, thus, limiting their potentially widespread use. The need to deliver vaccines via alternative routes of administration (e.g. the mucosal routes) in order to enhance their efficacy and compliance has set new requirements in basic and applied research to evaluate their efficacy and safety. Cholera toxin (CT) and labile enterotoxin (LT) mutants given along with intranasal or oral vaccines are strong candidates as mucosal adjuvants. Their potential reactogenicity is still matter of discussions, although available data support the notion that the effects due to their binding to the cells and those due to the enzymatic activity can be kept separated. Finally, adjuvanticity is more often evaluated in terms of antigen-specific antibody titers induced after parenteral immunization. It is known that, in many instances, antigen-specific antibody titers do not correlate with protection. In addition, very little is known on parameters of cell-mediated immunity which could be considered as surrogates of protection. Tailoring of new adjuvants for the development of vaccines with improved immunogenicity/efficacy and reduced reactogenicity will represent one of the major challenges of the ongoing vaccine-oriented research.
传统上按照经验方法研发的疫苗，其免疫原性问题往往有限，这可能是因为它们所含活性成分的纯度较低。将新技术应用于疫苗研发正促使生产出纯度更高的（如重组）抗原，然而，与上一代疫苗相比，这些抗原的免疫原性往往较差。寻找新型疫苗佐剂涉及到与其潜在局限性相关的问题。自70多年前引入铝盐作为疫苗佐剂以来，仅有一种佐剂被批准用于人类。其中一些新型疫苗佐剂的研发受到其不可接受的反应原性的阻碍。此外，一些佐剂与某些抗原强烈作用，但与其他抗原则不然，因此限制了它们可能的广泛应用。为提高疫苗效力和顺应性而需要通过替代给药途径（如黏膜途径）接种疫苗，这对基础研究和应用研究提出了新要求，以评估其效力和安全性。与鼻内或口服疫苗一起使用的霍乱毒素（CT）和不耐热肠毒素（LT）突变体是强有力的黏膜佐剂候选物。尽管现有数据支持这样的观点，即它们与细胞结合产生的效应和酶活性产生的效应可以分开，但它们潜在的反应原性仍是讨论的话题。最后，佐剂活性更多地是根据经肠道外免疫后诱导的抗原特异性抗体滴度来评估。众所周知，在许多情况下，抗原特异性抗体滴度与保护作用并不相关。此外，对于可被视为保护替代指标的细胞介导免疫参数，人们了解甚少。定制新型佐剂以研发具有更高免疫原性/效力和更低反应原性的疫苗，将是当前疫苗导向研究的主要挑战之一。
