Studies of vaccines derived from carbohydrate antigens have seen great progress. Synthetic carbohydrate-based vaccines, including polysaccharides, neoglycoproteins, and neoglycolipids, have been explored or used to prevent and treat bacterial and viral infections, cancer, and other diseases. This book discusses these developments with a focus on glycoimmunology including the design, synthesis, evaluation, and applications of various carbohydrate-based vaccines. It approaches vaccine design from a chemistry and molecular focus, different from past work but in-tune with current advances, providing a single, convenient source of state-of-the-art information from leading authorities in the field.

• Preface. Contributors. Chapter 1: Glycobiology and Immunology (Udayanath Aich and Kevin J. Yarema). 1. Introduction. 2. Glycobiology. 2.1 Glycosylation - Is it Worth the Cost. 2.2 Glycan Biosynthesis - A Dauntingly Complex Process. 2.3 Glycoproteins. 2.4 Lipid-based Glycans. 2.5 Polysaccharides: Glycosaminoglycans (GAGs) and Bacterial Capsular Components. 3. The Immune System. 3.1 Introductory Comments. 3.2 Overview of the Immune System. 3.3 Glycoimmunobiology. 3.4 The Interplay between Glycosylation and Sugars is a Two Way Street. 4. Carbohydrate Antigens. 4.1 Carbohydrate Antigens in Man. 4.2 Carbohydrates and Pathogens. 4.3 Carbohydrate-based Vaccines. 4.4 Concluding Comments: Building on Success. Acknowledgement. References Cited. Chapter 2: Preparation of Glycoconjugate Vaccines (Wei Zou and Harold J. Jennings). 1. Introduction. 2. Capsular Polysaccharide-Protein Conjugates. 2.1 Haemophilus influenzae type b. 2.2 Streptococcus pneumoniae. 2.3 Neisseria meningitidis. 2.4 Salmonella typhi Vi. 2.5 Group B streptococcus. 2.6 Staphylococcus aureus type 5 and 8. 3. Lipopolysaccharide (LPS) and Lipooligosaccharide (LOS) conjugates. 3.1 Escherichia coli O157. 3.2 Vibrio cholerae O1 and O139. 3.3 Shigella dysenteriae type 1, sonnei and flexneri 2a. 3.4 Neisseria meningitidis and Non-typeable Haemophilus influenzae. 4. Total synthetic glycoconjugate vaccines. References Cited. Chapter 3: Adjuvants for Protein- and Carbohydrate-Based Vaccines (Bruno Guy). 1. Introduction. 2. Initiation and stimulation of adaptive responses. 3. Old adjuvants and formulations. 3.1. Aluminium. 3.2. Emulsions. 3.3. Saponins, QS21, ISCOMS. 3.4. Liposomes, microparticles. 3.5. Antigen/formulation targeting. 3.6. Induction of CD8 CTLs with soluble antigens. 4. Renaissance of innate immunity. 4.1. TLRs, agonists and roles. 4.2. Non-TLRs innate receptors. 4.3. Other receptors involved in antigen capture and recognition. 5. From basic research to practical applications: identification of new adjuvants. 5.1. TLR synthetic agonists. 5.2. Combination of PRR agonists. 6. Adjuvants for carbohydrate-based vaccines. 6.1. Td and Ti B cell responses. 6.2. Adjuvants for free polysaccharides (Ti antigens). 6.3. Adjuvants for glycoconjugate vaccines (T-dependent antigens). 7. Combinations of adjuvants: preclinical and clinical developments. 8. Immunomodulation of existing responses: adjuvants for therapeutic vaccines. 9. Take another route. 9.1. Adjuvants for mucosal immunization. 9.2. Epidermal or intradermal routes. 10. Practical aspects of adjuvant development. 10.1. Regulatory aspects. 10.2. Safety versus efficacy: risk/benefit ratio. 11. Preclinical models used in adjuvant development. 11.1. Animal models. 11.2. In vitro models. 12. Conclusions and perspectives. Acknowledgement. References Cited. Chapter 4: Carbohydrate-Based Antibacterial Vaccines (Robert A. Pon and Harold J. Jennings). 1. Introduction. 2. Polysaccharide and glycoconjugate immunobiology. 3. Deficiencies in the human immune response to polysaccharides. 4. Glycoconjugate vaccines. 5. Haemophilus influenzae. 5.1 Hib polysaccharides. 5.2 Hib conjugate vaccines. 6. Neisseria meningitidis. 6.1 Meningococcal polysaccharide vaccines. 6.2 Meningococcal conjugate vaccines. 7. Streptococcus pneumoniae. 7.1 Impact on invasive pneumococcal disease. 7.2 Impact on acute otitis media. 8. Group B Streptococcus. 9. Salmonella typhi. 10. Conjugate vaccines- Future concerns. 11. Summary. References Cited. Chapter 5: Carbohydrate-Based Antiviral Vaccines (Benjamin M. Swarts and Zhongwu Guo). 1. Introduction. 2. Viral Glycosylation. 2.1 Viral N-glycosylation. 2.2 Carbohydrates of HIV. 2.3 Carbohydrates of influenza A virus. 2.4 Carbohydrates in hepatits C virus. 2.5 Carbohydrates in other viruses. 3. Vaccine and Drug Development. 3.1 HIV. 3.2. Influenza A virus. 3.3. Hepatitis C virus. 4. Conclusions. Acknowledgement. References Cited. Chapter 6: Carbohydrate-Based Antiparasitic Vaccines (Faustin Kamena, Xinyu Liu and Peter H. Seeberger). 1. Introduction. 2. GPI-based antimalarial vaccine. 2.1 GPI as a malaria toxin. 2.2 Synthetic GPI as antitoxic malaria vaccine candidate. 2.3 Synthetic GPI microarray to define antimalarial antibody response. 3. LPG-based antileishmanial vaccine. 3.1 LPG in leishmaniasis pathogenesis. 3.2 Synthetic phosphoglycan repeating unit as potential antileishmanial vaccine. 3.3 Synthetic LPG cap oligosaccharide as antileishmanial vaccine candidate. 4. Other examples. 4.1 Fucosylated N-glycan as potential vaccine lead against schistosomiasis. 4.2 GPIs as potential vaccine lead against toxoplasmosis and chagas' disease. 5. Perspectives and Future Challenge. Acknowledgement. References cited. Chapter 7: Carbohydrate-Based Antifungal Vaccines (Magdia De Jesus, Liise-anne Pirofski and Arturo Casadevall). 1. Introduction. 2. Terminology. 2.1 Vaccination vs Immunization. 2.2 Toxoids. 2.3 Glycoconjugates. 3. antifungal Glycoconjugate vaccines. 3.1 C. neoformans polysaccharide-protein conjugates. 3.2 Development of alternative vaccines in C. neoformans. 3.3 C. albicans mannan-protein conjugates. 3.4 beta-Glucan-protein conjugates. 4. Antifungal vaccines and the immune system. 5. Summary. Acknowledgement. References Cited. Chapter 8: Cancer-Associated and Related Glycosphingolipid Antigens (Steve Levery). 1. Introduction. 2. Structural Classification of Antigens. 3. Abnormal Expression of Glycosphingolipid (GSL) Glycan Structures in Cancer Tissues. 4. Discussion of Delected Antigens. 4.1 Globo-series and related antigens. 4.2 Ganglio-series antigens. 4.3 Lacto-series (Type 1 chain
• Lcn) antigens. 4.4 Neolacto-series (Type 2 chain
• nLcx) antigens. 5. Other Antigens. 5.1 Lea-Lea and Leb-Lea. 5.2 Lea-Lex. Acknowledgement. References Cited. Chapter 9: Synthetic Carbohydrate-Based Anticancer Vaccines (Therese Buskas, Pamela Thompson, and Geert-Jan Boons). 1. Introduction to Cancer Vaccines. 2. Tumor-Associated Carbohydrate Antigens (TACAs). 3. Carbohydrate-Based Cancer Vaccines. 4. Humoral Immune Response to Carbohydrates. 5. MHC Mediated Immune Response to Glycopeptides. 6. Toll-like Receptors and the Link Between Innate and Adaptive Immunity. 7. Chemical synthesis of tumor-associated carbohydrates and glycopeptides. 8. Semi-synthetic carbohydrate-based cancer vaccines. 9. Fully synthetic carbohydrate-based cancer vaccines. 10. B-epitope and receptor ligand di-epitope constructs. 11. B- and T-cell di-epitope constructs. 12. Tri-component vaccines. References. Chapter 10: Glycoengineering of Cell Surface Sialic Acid and Its Application to Cancer Immunotherapy (Zhongwu Guo). 1. Introduction. 2. Engineering of Cell Surface Sialic Acids. 3. Sialic Acid engineering for Modulation of Cell Surface Reactivity. 4. Sialic Acids engineering for Cancer Immunotherapy. 5. Summary. Acknowledgement. References Cited. Chapter 11: Therapeutic Cancer Vaccines: Clinical Trials and Applications (Hans H. Wandall and Mads A. Tarp). 1. Introduction. 2. Innate and adaptive immunity in relation to cancer immunotherapy. 3. Design issues for clinical cancer vaccine trials. 4. Clinical development of cancer vaccines. 5. Proof of principle trials. 5.1 Toxicity and pharmacokinetics. 5.2 Dose and administration schedule. 5.3 Endpoints: Biological activity and clinical activity. 6. Efficacy Trials. 7. Clinical endpoints in efficacy trials. 8. Challenges in vaccine development. 9. Defining the target tumor-associated antigens. 10. Production and storage issues. 11. Clinical trials. 11.1 Glycosphingolipid-based vaccines. 11.2 O-glycan-based vaccines. 12. Conclu