Carbohydrate vaccines

Overview

Emerging field of glycoimmunology: vaccines using carbohydrates!

The field of carbohydrate vaccines is becoming more relevant and more useful with the development of new glycomic technology. Now there are better ways for glycan analysis, synthesis, structure determination, and array formation.

Vaccines should be examined in terms of their pathogen source (e.g. bacterial, fungal, cancer)

Importance:

• Way to combat increasing antibiotic resistance

Background

Four sources need to be considered for a carbohydrate vaccine: 1) antigen source, 2) carrier, 3) conjugation method, 4) adjuvant (Astronomo).

Current issues in their development: 1) poor immunogenicity, 2) heterogeneity, 3) antigenic mimicry of self glycans, and 4) identification and access to protective epitopes.

Viruses often take advantage of surface carbohydrates (glycans) for binding epitopes.

T-cell immune responses are activated by carbohydrate antigens (Astronomo), while the CD4+ helper T cells are activated by proteins.Carbohydrate-specific antibodies usually have lower affinity than protein-specific antibodies. Most likely this is because carbohydrates have less conformational flexibility when present in its complex form.

The glycan antigens themselves (surface carbohydrates) are very diverse which gives rise to their complexity and specificity.

Advantages:

• Pathogenic cell surfaces usually have distinct and characteristic carbohydrate proteins which can be targeted (Hecht)
• The fast mutation rates in pathogens does not directly affect the carbohydrates on the cell surface (Hecht)

Disadvantages:

• Often difficult to isolate carbohydrates (Hecht)
• Not immunogenic for children under two, the elderly, and immunocompromised individuals. (Vliegenthart)

Definitions

Standard definition of vaccines: "provide protection by inducing humoral and/or cellular immunity to disease-causing pathogens." (Astronomo)

Lectin - sugar binding protein

Glycan - polysaccharide or oligosaccharide

Papers on the topic

Currently these are mostly review papers, we will need to start looking at primary articles.

Astronomo, Rena D., & Burton, Dennis R. Carbohydrate vaccines: developing sweet solutions to sticky situations? (2010). Nature 9, 308-324. http://www.nature.com/nrd/journal/v9/n4/full/nrd3012.html

Frank, Martin., & Schlossing, Siegfried. Bioinformatics and molecular modeling in glycobiology. (2010). Cell. Mol. Life Sci. 67, 2749-2772. http://www.ncbi.nlm.nih.gov/pubmed/20364395 (about carbohydrates in general, might need it as reference)

Hecht, Marie-Lyn., Stallforth, Pierre., Silva, Daniel Varon., Adibekian, Alexander.,& Seeberger, Peter H. Recent advances in carbohydrate-based vaccines.(2009). Current Opinion In Chemical Biology 13, 354-359. http://www.ncbi.nlm.nih.gov/pubmed/19560394

Huang, YL., & Wu, CY. Carbohydrate-based vaccines: challenges and opportunities. (2010). Expert Rev. Vaccines 11, 1257-1274. http://www.ncbi.nlm.nih.gov/pubmed/21087106 (abstract)

Lucas, AH., Apicella, MA., & Taylor, CE. Carbohydrate moieties as vaccine candidates. (2005). Clin. Infect. Dis. 41(5), 705-7012. http://www.ncbi.nlm.nih.gov/pubmed/16080094

Vliegenthart, Johannes F. G. Carbohydrate based vaccines. (2006). FEBS Letters 580, 2945-2950. http://www.ncbi.nlm.nih.gov/pubmed/16630616