Carbohydrate vaccines: developing sweet solutions to sticky situations?

• Published in: Nature reviews. Drug discovery Vol. 9; no. 4; pp. 308 - 324
• Main Authors: Astronomo, Rena D, Burton, Dennis R
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2010; Nature Publishing Group
• Subjects: 631/154/51/1868; 631/45/221; Animals; Biomedical and Life Sciences; Biomedicine; Biotechnology; Cancer Research; Carbohydrates; Carbohydrates - chemistry; Carbohydrates - immunology; Drug Delivery Systems; Drug Design; Epitopes; Glycoconjugates - chemistry; Glycoconjugates - immunology; Glycomics - methods; Health aspects; Hib vaccines; Humans; Medicinal Chemistry; Molecular Medicine; Pharmacology/Toxicology; Physiological aspects; Polysaccharides - metabolism; Properties; review-article; Vaccines; Vaccines - chemistry; Vaccines - immunology; United States
• ISSN: 1474-1776; 1474-1784
• DOI: 10.1038/nrd3012

Key Points Carbohydrate structures decorate the surface of pathogens and malignant cells and could be exploited as potential targets for vaccine design. Indeed, most vaccines against bacterial infections are carbohydrate vaccines. The steady increase in drug resistance has catalysed a renewed interest in carbohydrate vaccine development against a wide range of pathogens (that is, bacteria, fungi, protozoa, helminths and viruses) as well as cancer. Recent advances in glycomics, particularly carbohydrate synthesis, protein conjugation methods, analysis, structural determination and array fabrication, are accelerating progress in the carbohydrate vaccine field. For example, improvements in synthetic methods facilitate the identification and evaluation of potential glycan antigens by providing usable amounts of pure material. A number of challenges are associated with targeting glycan structures in a vaccine context. Generally speaking, the main challenges include the poor immunogenicity of carbohydrates, low affinity of protein–carbohydrate interactions, structural diversity of glycans between species and/or strains and microheterogeneity. A major breakthrough in improving immunogenicity came with the discovery that chemical conjugation of glycans to a suitable protein scaffold can convert carbohydrates from T-cell-independent antigens to T-cell-dependent antigens. Co-administration of adjuvants has also been shown to improve the strength of the immune response against carbohydrate immunogens. Certain pathogen-associated carbohydrate antigens as well as tumour-associated carbohydrate antigens may be poorly immunogenic owing to the expression of similar or identical structures in humans, albeit at a lower density or during early developmental stages. To address this issue, strategies are being developed to better mimic the presentation (for example, clustering) of glycans on target cells or organisms and to introduce conservative chemical modifications to the target antigens to render them more immunogenic. The ability to elicit specific, potent and long-lasting anti-carbohydrate antibody responses that are therapeutic and/or protect against diseases caused by pathogens or tumours is a complex goal dependent on the antigen(s) and the disease. In many cases, the mechanisms of disease and potential of antibody-mediated protection need further clarification to facilitate the development of more effective vaccines or passive immunization approaches. Antibiotic drug resistance has increased interest in developing vaccines against carbohydrate structures on the surface of bacterial pathogens. Astronomo and Burton examine recent progress in the identification, synthesis and evaluation of glycan epitopes found not only on bacteria, but also on protozoa, helminths, viruses, fungi and cancer cells for vaccine design. Recent technological advances in glycobiology and glycochemistry are paving the way for a new era in carbohydrate vaccine design. This is enabling greater efficiency in the identification, synthesis and evaluation of unique glycan epitopes found on a plethora of pathogens and malignant cells. Here, we review the progress being made in addressing challenges posed by targeting the surface carbohydrates of bacteria, protozoa, helminths, viruses, fungi and cancer cells for vaccine purposes.