Carbohydrate-Based Vaccines and Immunotherapies

Zhongwu Guo is a Professor of Chemistry at Wayne State University. The winner of the American Chemical Society's 2005 New Investigator Award in Carbohydrate Chemistry, Dr. Guo serves on the editorial board of the Journal of Carbohydrate Chemistry, speaks regularly at international conferences, and has authored more than ninety peer-reviewed publications. Geert-Jan Boons is a Franklin Professor of Chemistry at the Complex Carbohydrate Research Center (CRCR) of the University of Georgia. The winner of the European Carbohydrate Association's Carbohydrate Research Award for Creativity in Carbohydrate Science, and the American Chemical Society's Horace Isbell Award, Dr. Boons serves on the editorial boards of Journal of Carbohydrate Chemistry and Advances in Carbohydrate Chemistry and Biochemistry.

• Preface xvContributors xvii1 Glycobiology and Immunology 1Udayanath Aich and Kevin J. Yarema1.1 Introduction 11.2 Glycobiology 31.2.1 Glycosylation—Is It Worth the Cost? 31.2.2 Glycan Biosynthesis—A Dauntingly Complex Process 61.2.3 Glycoproteins 71.2.4 Lipid-Based Glycans 161.2.5 Polysaccharides: Glycosaminoglycans and Bacterial Capsular Components 181.3 The Immune System 201.3.1 Introductory Comments 201.3.2 Overview of the Immune System 201.3.3 Glycoimmunobiology 231.3.4 Interplay between Glycosylation and Sugars: a Two-Way Street 271.4 Carbohydrate Antigens 281.4.1 Carbohydrate Antigens in Humans 281.4.2 Carbohydrates and Pathogens 301.4.3 Carbohydrate-Based Vaccines 341.4.4 Concluding Comments: Building on Success 38Acknowledgment 38References 382 Preparation of Glycoconjugate Vaccines 55Wei Zou and Harold J. Jennings2.1 Introduction 552.2 Capsular Polysaccharide–Protein Conjugates 562.2.1 Haemophilus influenzae Type b 562.2.2 Streptococcus pneumoniae 592.2.3 Neisseria meningitidis 602.2.4 Salmonella typhi Vi 642.2.5 Group B Streptococcus 652.2.6 Staphylococcus aureus Types 5 and 8 672.3 Lipopolysaccharide (LPS) and Lipooligosaccharide (LOS) Conjugates 692.3.1 Escherichia coli O157 692.3.2 Vibrio cholerae O1 and O139 702.3.3 Shigella dysenteriae Type 1, sonnei and flexneri 2a 712.3.4 Neisseria meningitidis and Nontypeable Haemophilus influenzae 722.4 Total Synthetic Glycoconjugate Vaccines 76References 793 Adjuvants for Protein- and Carbohydrate-Based Vaccines 89Bruno Guy3.1 Introduction 893.2 Initiation and Stimulation of Adaptive Responses 903.3 “Old” Adjuvants and Formulations 923.3.1 Aluminum 923.3.2 Emulsions 933.3.3 Saponins, QS21, and ISCOMS 943.3.4 Liposomes and Microparticles 943.3.5 Antigen/Formulation Targeting 943.3.6 Induction of CD8 CTLs with Soluble Antigens 953.4 Renaissance of Innate Immunity 953.4.1 Toll-Like Receptors: Agonists and Roles 953.4.2 Non-TLRs Innate Receptors 973.4.3 Other Receptors Involved in Antigen Capture and Recognition 973.5 From Basic Research to Practical Applications: Identification of New Adjuvants 973.5.1 TLR Synthetic Agonists 973.5.2 Combination of PRR Agonists 983.6 Adjuvants for Carbohydrate-Based Vaccines 983.6.1 Td and Ti B-Cell Responses 993.6.2 Adjuvants for “Free” Polysaccharides (Ti Antigens) 993.6.3 Adjuvants for Glycoconjugate Vaccines (T-Dependent Antigens) 1003.7 Combinations of Adjuvants: Preclinical and Clinical Developments 1013.8 Immunomodulation of Existing Responses: Adjuvants for Therapeutic Vaccines 1013.9 Take Another Route 1023.9.1 Adjuvants for Mucosal Immunization 1023.9.2 Epidermal or Intradermal Routes 1023.10 Practical Aspects of Adjuvant Development 1033.10.1 Regulatory Aspects 1033.10.2 Safety versus Efficacy: Risk–Benefit Ratio 1033.11 Preclinical Models Used in Adjuvant Development 1043.11.1 Animal Models 1043.11.2 In vitro Models 1043.12 Conclusions and Perspectives 106Acknowledgment 106References 1064 Carbohydrate-Based Antibacterial Vaccines 117Robert A. Pon and Harold J. Jennings4.1 Introduction 1174.2 Polysaccharide and Glycoconjugate Immunobiology 1184.3 Deficiencies in the Human Immune Response to Polysaccharides 1204.4 Glycoconjugate Vaccines 1214.5 Haemophilus influenzae 1224.5.1 Hib Polysaccharides 1224.5.2 Hib Conjugate Vaccines 1234.6 Neisseria meningitidis 1254.6.1 Meningococcal Polysaccharide Vaccines 1264.6.2 Meningococcal Conjugate Vaccines 1264.7 Streptococcus pneumoniae 1334.7.1 Impact on Invasive Pneumococcal Disease 1394.7.2 Impact on Acute Otitis Media 1404.8 Group B Streptococcus 1404.9 Salmonella typhi 1454.10 Conjugate Vaccines: Future Concerns 1464.11 Summary 147References 1485 Carbohydrate-Based Antiviral Vaccines 167Benjamin M. Swarts and Zhongwu Guo5.1 Introduction 1675.2 Viral Glycosylation 1685.2.1 Viral N-glycosylation 1685.2.2 Carbohydrates of HIV 1705.2.3 Carbohydrates of Influenza A Virus 1725.2.4 Carbohydrates in Hepatitis C Virus 1735.2.5 Carbohydrates in Other Viruses 1745.3 Vaccine and Drug Development 1745.3.1 Human Immune Deficiency Virus 1745.3.2 Influenza A Virus 1815.3.3 Hepatitis C Virus 1825.4 Conclusions 182Acknowledgment 183References 1836 Carbohydrate-Based Antiparasitic Vaccines 195Faustin Kamena, Xinyu Liu, and Peter H. Seeberger6.1 Introduction 1956.2 GPI-Based Antimalarial Vaccine 1976.2.1 GPI as a Malaria Toxin 1976.2.2 Synthetic GPI as Antitoxic Malaria Vaccine Candidate 1986.2.3 Synthetic GPI Microarray to Define Antimalarial Antibody Response 2006.3 LPG-Based Antileishmanial Vaccine 2016.3.1 LPG in Leishmaniasis Pathogenesis 2016.3.2 Synthetic Phosphoglycan Repeating Unit as Potential Antileishmanial Vaccine 2036.3.3 Synthetic LPG Cap Oligosaccharide as Antileishmanial Vaccine Candidate 2046.4 Other Examples 2056.4.1 Fucosylated N-glycan as Potential Vaccine Lead against Schistosomiasis 2056.4.2 GPIs as Potential Vaccine Lead against Toxoplasmosis and Chagas’ Disease 2076.5 Perspectives and Future Challenge 208Acknowledgment 209References 2097 Carbohydrate-Based Antifungal Vaccines 215Magdia De Jesus, Liise-anne Pirofski, and Arturo Casadevall7.1 Introduction 2157.2 Terminology 2167.2.1 Vaccination versus Immunization 2167.2.2 Toxoids 2167.2.3 Glycoconjugates 2167.3 Antifungal Glycoconjugate Vaccines 2177.3.1 C. neoformans Polysaccharide–Protein Conjugates 2177.3.2 Development of Alternative Vaccines for C. neoformans 2207.3.3 C. albicans Mannan–Protein Conjugates 2207.3.4 β-Glucan–Protein Conjugates 2217.4 Antifungal Vaccines and the Immune System 2227.5 Summary 223Acknowledgment 224References 2248 Cancer-Associated and Related Glycosphingolipid Antigens 227Steven B. Levery8.1 Introduction 2278.2 Structural Classification of Antigens 2288.3 “Abnormal” Expression of Glycosphingolipid (GSL) Glycan Structures in Cancer Tissues 2288.4 Discussion of Selected Antigens 2348.4.1 Globo-Series and Related Antigens 2348.4.2 Ganglio-Series Antigens 2378.4.3 Lacto-Series (Type 1 Chain; Lcn) Antigens 2418.4.4 Neolacto-Series (Type 2 Chain; nLcx) Antigens 2428.5 Other Antigens 2488.5.1 Lea-Lea and Leb-Lea 2488.5.2 Lea-Lex 249Acknowledgment 250References 2509 Semisynthetic and Fully Synthetic Carbohydrate-Based Cancer Vaccines 263Therese Buskas, Pamela Thompson, and Geert-Jan Boons9.1 Introduction to Cancer Vaccines 2639.2 Tumor-Associated Carbohydrate Antigens (TACAs) 2649.3 Carbohydrate-Based Cancer Vaccines 2679.4 Humoral Immune Response to Carbohydrates 2679.5 MHC-Mediated Immune Response to Glycopeptides 2699.6 Toll-Like Receptors and the Link Between Innate and Adaptive Immunity 2709.7 Chemical Synthesis of Tumor-Associated Carbohydrates and Glycopeptides 2719.8 Semisynthetic Carbohydrate-Based Cancer Vaccines 2769.9 Fully Synthetic Carbohydrate-Based Cancer Vaccines 2799.10 B-Epitope and Receptor Ligand Di-Epitope Constructs 2799.11 B- and T-Cell Di-Epitope Constructs 2849.12 Tricomponent Vaccines 288References 29210 Glycoengineering of Cell Surface Sialic Acid and Its Application to Cancer Immunotherapy 313Zhongwu Guo10.1 Introduction 31310.2 Engineering of Cell Surface Sialic Acids 31410.3 Sialic Acid Engineering for Modulation of Cell Surface Reactivity 31810.4 Sialic Acid Engineering for Cancer Immunotherapy 32110.5 Summary 325Acknowledgment 326References 32611 Therapeutic Cancer Vaccines: Clinical Trials and Applications 333Hans H. Wandall and Mads A. Tarp11.1 Introduction 33311.2 Innate and Adaptive Immunity in Relation to Cancer Immunotherapy 33411.3 Design Issues for Clinical Cancer Vaccine Trials 33711.4 Clinical Development of Cancer Vaccines 33711.5 Proof of Principle Trials 33811.5.1 Toxicity and Pharmacokinetics 33911.5.2 Dose and Administration Schedule 33911.5.3 Endpoints: Biological Activity and Clinical Activity 33911.6 Efficacy Trials 34011.7 Clinical Endpoints in Efficacy Trials 34011.8 Challenges in Vaccine Development 34111.9 Defining the Target Tumor-Associated Antigens 34211.10 Production and Storage Issues 34411.11 Clinical Trials 34511.11.1 Glycosphingolipid-Based Vaccines 34711.11.2 O-glycan-Based Vaccines 35111.12 Conclusions 354Acknowledgment 355References 35512 Carbohydrates as Unique Structures for Disease Diagnosis 367Kate Rittenhouse-Olson12.1 Introduction 36712.2 Viruses 36912.2.1 Infectious Mononucleosis 36912.2.2 Influenza A and B 37012.3 Bacteria 37112.3.1 Streptococcus pyogenes 37112.3.2 Groups A, B, C, D, F, and G Streptococcus 37112.3.3 Streptococcus pneumoniae 37312.3.4 Meningitis 37312.3.5 Chlamydia trachomatis 37412.3.6 Future 37412.4 Fungi 37412.4.1 Aspergillus fumigatus 37512.4.2 Invasive Candidiasis 37512.4.3 Cryptococcus neoformans 37512.4.4 Histoplasma capsulatum 37612.5 Parasites 37712.5.1 Echinococcus multilocularis 37712.5.2 Clonorchis sinensis 37812.5.3 Trichinella 37812.5.4 Schistosoma mansoni 37812.6 Autoimmunity 37812.6.1 Diabetes 37812.6.2 Cold Agglutinin Disease 37912.6.3 Inflammatory Bowel Disease 38012.7 Tumors 38012.7.1 Bladder 38112.7.2 Breast 38112.7.3 Colon 38212.7.4 Liver 38212.7.5 Lung 38312.7.6 Melanoma 38412.7.7 Ovarian 38512.7.8 Pancreatic 38612.7.9 Prostate 38712.8 Inherited or Acquired Disorders of Glycosylation 388References 388Index 395