Antigens carbohydrate-based vaccines

In addition, carbohydrate conjugates can be utilized to develop carbohydrate-based vaccines for treatment of diseases in which carbohydrate toxins or antigens, respectively, are involved. Thus, fully synthetic glycoconjugates might be developed into vaccines for malaria, and other parasites such as different bacteria, tuberculosis, tropical diseases, leishmaniasis and the Influenzae virus. 

Cancer. The development of carbohydrate-based vaccines designed to activate T-cells targeting of cancer cells has been pursued for some time. The goal of a cancer vaccine is to make the host immune system responsive to antigens characteristic of cancer cells. Several carbohydrate-based therapeutics that have now reached clinical trials seek to estab-... 

Gold NPs have been used as multivalent and multifunctional platforms for tumor-associated carbohydrate antigens in combination with suitable immunogenic carriers to develop carbohydrate-based vaccines. The pioneering group of Penades was the first to identify gold NPs as potential scaffolds for vaccine preparation [84]. 

Allen JR, Harris CR, Danishefsky SJ. Pursuit of optimal carbohydrate-based anticancer vaccines preparation of a multiantigenic unimolecular glycopeptide containing the Tn, MBrl, and Lewisy antigens. J Am Chem Soc 2001 123 1890-1897. 

T. Buskas, S. Ingale, and G.-J. Boons, Towards a fully synthetic carbohydrate-based anticancer vaccine Synthesis and immunological evaluation of a lipidated glycopeptide containing the tumor-associated Tn antigen, Angew. Chem. Int. Ed., 44 (2005) 5985-5988. 

Our rationale was that if SARS-CoV expressed antigenic carbohydrate structures, then immunizing animals using the whole virus-based vaccines would have elicited specific antibodies for these structures. In addition, if SARS-CoV displayed a carbohydrate structure that mimics host cellular glycans, then vaccinated animals may develop antibodies with autoimmune reactivity to their corresponding cellular glycans. 

The lipid-core peptide (LCP) system (Toth et al. 1993 Moyle et al. 2003) (Fig. 11.3) is a delivery system which conjugates synthetic lipoamino acids (a-amino acids with long alkyl side chains) through a polylysine MAP system (or a carbohydrate) (McGeary et al. 2001, 2002) to multiple copies of one or several different peptide antigens. The LCP system induces similar immune responses when LCP-based vaccines are co-administered with conventional adjuvants and represents a promising system for mucosal vaccine development. 

Beside the ABO blood group system a number of additional carbohydrate-based antigenic determinants are known (O Table 2), which are, however, not only recognized by antibodies. Some of them are more highly expressed on tumor cells and therefore can be described as tumor-associated antigens [115]. Synthetic tumor-associated antigens such as Lewis y or Globo H have been used in the development of antitumor vaccines [116,117]. 

In addition to exposed peptide motifs, the generation of aberrantly sialylated carbohydrate moieties provides yet another means of differentiating between cells expressing normal or cancer-associated mucins in vivo (see O Sect. 4). Chemical synthesis allows a potentially unlimited number of vaccine formulations to be constmcted incorporating one, or a combination of antigenic mucin-based carbohydrate structures. 

The pharmaceutical impact of carbohydrate-based therapeutics can also be seen in the agents now under evaluation in pre-clini-cal and clinical development. For example, synthetic carbohydrate chains, modeled on tumor cell antigens but modified to stimulate an immune response, are being used to develop novel cancer vaccines. 

Cells express unique carbohydrate structures upon carcinogenic transformation. Therefore, carbohydrate-based antigens offer the potential for a targeted immuno-therapeutic approach to the treatment of certain forms of cancer. Although carbohydrate cancer vaccines have been shown to be safe and to mediate con lement-dependent and/or antibody-dependent cell-mediated cytotoxicity, only a limited number of carbohydrate structures have been evaluated in preclinical and clinical settings. ... 

Scheme 17 KLH-based vaccine exposing five tumour-associated carbohydrate antigens linked to an unnatural peptide.

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