Glycodendrimers as functional antigens and antitumor vaccines

Abstract

Glycodendrimers have advantageous characteristics of providing potent immunostimulating and adjuvant properties in vaccine preparation due to their molecularly defined multivalent scaffolds together with their abundant architectural variations. Their versatile syntheses allow the production of highly defined conjugates with small antigens. An overview of the use of dendrimers as carriers of carbohydrate antigens including constructs that have built-in adjuvant properties and as stand-alone adjuvants that can be mixed with carbohydrate antigens to provide efficient vaccine formulations is provided. A brief description of the innate and adaptive immune responses toward glycoconjugates is provided to allow better understanding and basic constituent requirements for future design. The necessary distinction between antigens and immunogens (vaccines) is also discussed. To counterbalance the poor immunogenicity and T-cell independent characteristics of carbohydrate antigens, chemists have developed original hybrid molecules aimed at targeting specific pattern-recognition receptors to trigger competent immune cell proliferations and protective antibody production. Although early glycodendrimers were found to lack immunogenicity, these architecturally impressive nanomolecules were shown to bind avidly to various carbohydrate binding proteins, including antibodies. More recently, the hitherto non-immunogenic dendritic components have been successfully used as adjuvants and carriers to direct other molecules to immunocompetent cells. Commendable examples against tumor associated carbohydrate antigens will illustrate the immunochemical strategies engaged in the development of potent and exclusively synthetic carbohydrate-based anticancer vaccines.