What are the limits of adjuvanticity?

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 technologi es to vaccine development is leading to the production of purer (e.g. recom binant) antigens which, however, tend to have a poorer immunogenicity as co mpared to vaccines of the previous generation. The search for new vaccine a djuvants involves issues related to their potential limits. Since the intro duction of aluminium salts as vaccine adjuvants more than 70 years ago, onl y one adjuvant has been licensed for human use. The development of some of these new vaccine adjuvants has been hampered by their inacceptable reactog enicity. In addition, some adjuvants work strongly with some antigens but n ot with others, thus, limiting their potentially widespread use. The need t o deliver vaccines via alternative routes of administration (e.g. the mucos al routes) in order to enhance their efficacy and compliance has set new re quirements in basic and applied research to evaluate their efficacy and saf ety. Cholera toxin (CT) and labile enterotoxin (LT) mutants given along wit h intranasal or oral vaccines are strong candidates as mucosal adjuvants. T heir potential reactogenicity is still matter of discussions, although avai lable 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. Finall y, adjuvanticity is more often evaluated in terms of antigen-specific antib ody titers induced after parenteral immunization. It is known that, in many instances, antigen-specific antibody titers do not correlate with protecti on. In addition, very little is known on parameters of cell-mediated immuni ty which could be considered as surrogates of protection. Tailoring of new adjuvants for the development of vaccines with improved immunogenicity/effi cacy and reduced reactogenicity will represent one of the major challenges of the ongoing vaccine-oriented research. (C) 2001 Elsevier Science Ltd. Al l rights reserved.