Carbohydrate-Based Vaccines and Immunotherapies

Description

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.

Table of Contents

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 ß-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. Conclusions.
• Acknowledgement.
• References Cited.

Chapter 12: Carbohydrates as Unique Structures for Disease Diagnosis (Kate Rittenhouse-Olson).

• 1. Introduction.
• 2. Viruses.
• 2.1 Infectious mononucleosis.
• 2.2 Influenza A and B.
• 3. Bacteria.
• 3.1 Streptococcus pyogenes.
• 3.2 Groups A, B, C, D, F and G Streptococcus.
• 3.3 Streptococcus pneumoniae.
• 3.4 Meningitis.
• 3.5 Chlamydia trachomatis.
• 3.6 Future.
• 4. Fungi.
• 4.1 Aspergillus fumigatus.
• 4.2 Invasive Candidiasis.
• 4.3 Cryptococcus neoformans.
• 4.4 Histoplasma capsulatum.
• 5. Parasites.
• 5.1 Echinococcus multilocularis.
• 5.2 Clonorchis sinensis.
• 5.3 Trichinella.
• 5.4 Schistomsoma mansoni.
• 6. Autoimmunity.
• 6.1 Diabetes.
• 6.2 Cold agglutinin disease.
• 6.3 Inflammatory bowel disease.
• 7. Tumors.
• 7.1 Bladder.
• 7.2 Breast.
• 7.3 Colon.
• 7.4 Liver.
• 7.5 Lung.
• 7.6 Melanoma.
• 7.7 Ovarian.
• 7.8 Pancreatic.
• 7.9 Prostate.
• 8. Inherited or acquired disorders of glycosylation.
• References Cited.