Front Cover 1
Mucosal Vaccines 4
Copyright Page 5
Contents 8
Contributors 16
Preface 20
Part I: Introduction 22
Chapter 1. Mucosal Immunoprophylaxis: An Introductory Overview 24
I. Introduction 24
II. Elements of Mucosal Immune System Involved in Immune Response 25
III. Immunoprophylaxis by the Mucosal Route 26
IV. Mucosal Adjuvants and Vaccine Delivery Systems 29
V. Potential Limitations of Mucosal Immunization 30
VI. Concluding Remarks 31
References 32
Part II: Principles of Mucosal Vaccination 36
Chapter 2. Application of Basic Principles of Mucosal Immunity to Vaccine Development 38
I. Introduction 38
II. Mucosal Immune System Organization 39
III. Characteristics of Regulatory T Cells in the Mucosal Immune System 41
IV. Multiple Roles for T Cells and Cytokines in Mucosal Immunity 44
V. The Role of Epithelial Cells in Mucosal Immunity 48
VI. Mucosal Effector Functions for IgA 49
VII. Diverse Antigen Delivery Systems for the Induction of Distinct Mucosal Immune Responses 50
VIII. Summary 54
References 54
Chapter 3. Antigen Uptake by M Cells for Effective Mucosal Vaccines 62
I . Introduction 62
II. Antigen Sampling across Stratified Epithelial Barriers 62
III. Antigen Sampling across Simple Epithelia 63
IV. M Cell Organization and Function 66
V. Differentiation of the FAE and M Cells 67
VI. Interactions of Microorganisms with M Cells 67
VII. M Cells and Mucosal Vaccine Strategies 68
VIII. Conclusions 72
References 72
Part III: Mucosal Modulation for Induction of Effective Immunity 78
Chapter 4. Cholera Toxin as a Mucosal Adjuvant 80
I. Introduction 80
II. The Molecular and Cellular Biology of Cholera Toxin 81
III. Cholera Toxin as a Mucosal Immunogen 82
IV. Cholera Toxin as a Mucosal Adjuvant: General Characteristics 82
V. Role of CT Subunits in Mucosal Adjuvanticity 84
VI. Site of Adjuvant Activity 85
VII. Antigen Uptake across Epithelium or into Lymphoid Follicles 86
VIII. Cellular Targets of Adjuvanticity 86
IX. Summary 89
References 89
Chapter 5. Use of Escherichia coli Heat-Labile Enterotoxin as an Oral Adjuvant 94
I. Introduction 94
II. Biological and Immunological Properties of Cholera Toxin and LT 95
III. Comparison of LT and CT 96
IV. Cellular Targets of Enterotoxin Action 97
V. Mucosal (Oral) Tolerance/Adjuvant Properties of LT 100
VI. Toward a Practical Adjuvant 101
VII. Summary 105
References 106
Chapter 6. Consideration of Mucosally Induced Tolerance in Vaccine Development 110
I. Introduction 110
II. Mucosal Immune System for Vaccines and Mucosally Induced Tolerance 111
III. Protein Vaccine Diphtheria Toxoid (DT) Induces Mucosal Tolerance 112
IV. Cholera Toxin B Subunit as Transmucosal and Carrier-Delivery System for Induction of Systemic Tolerance 114
V. Mechanisms of Oral Tolerance: Role of aß and .d T Cells 115
VI. Clinical Application of Oral Tolerance 118
References 119
Part IV: Current and New Approaches for Mucosal Vaccine Delivery 124
Chapter 7. Attenuated Salmonella as Vectors for Oral Immunization 126
I. Attenuated Salmonella for Use as Live Oral Vaccines 126
II. Vectors for the Expression of Foreign Epitopes 128
III. Expression of Heterologous Antigens by Attenuated Salmonella 129
IV. Use of Salmonella for Expression of Novel Antigens 133
V. Concluding Remarks 134
References 134
Chapter 8. Prospects for Induction of Mucosal Immunity by DNA Vaccines 140
I. Introduction 140
II. Immune Responses Induced by DNA Vaccines 140
III. Antigen Expression at Mucosal Sites 145
IV. Delivery of DNA to Mucosal Sites 145
V. Summary 146
References 146
Chapter 9. Recombinant BCG as Vector for Mucosal Immunity 150
I. Introduction 150
II. Background on BCG 151
III. rBCG as a Vaccine Delivery Vehicle : Expressing Foreign Proteins on the Surface of BCG 152
IV. rBCG as a Mucosal Vaccine Delivery Vehicle for the Upper Respiratory Tract 152
V. Conclusions 155
References 155
Chapter 10. Poliovirus Replicons as a Vector for Mucosal Vaccines 158
I. Introduction 158
II. The Poliovirus Genome 159
III. Development of Poliovirus as an Expression Vector 159
IV. Immunological Studies 162
V. Perspectives 165
Acknowledgments 165
References 165
Chapter 11. Recombinant Adenoviruses as Vectors for Mucosal Immunity 168
I . Introduction 168
II. Adenoviruses and Their Molecular Biology 168
III. Construction of Recombinant Adenovirus Vectors 169
IV. Adenovirus as a Vaccine Vector 170
V. Induction of Mucosal Immunity by Adenoviruses 171
VI. Advances in Adenovirus Vector Methodology and Future Directions 173
VII. Summary 174
References 175
Chapter 12. Poly(lactide-co-glycolide) Microencapsulation of Vaccines for Mucosal Immunization 180
I. Introduction 180
II. Characteristics of DL-PLG Microspheres 182
III. Microencapsulated Vaccines for Mucosal Immunization 186
IV. Future Directions 189
References 190
Chapter 13. ISCOMs, Liposomes, and Oil-Based Vaccine Delivery Systems 196
I . Introduction 196
II. Immunostimulating Complexes 198
III. Liposomes 200
IV. Oil-Based Delivery Systems 202
V. Concluding Remarks 203
References 204
Chapter 14. Passive Immunity for Protection against Mucosal Infections and Vaccination for Dental Caries 208
I. Introduction 208
II. Concept of Passive Immunity 208
III . Experimental Approach for Mucosal Passive Immunization against Infections 209
IV. Vaccination and Passive Immunization against Dental Caries 214
V. Summary and Prospects 215
References 215
Part V: Mucosal Vaccines for Bacterial Diseases 220
Chapter 15. Human Mucosal Vaccines for Salmonella typhi Infections 222
I. Introduction 222
II. Pathogenesis 222
III. Vaccines 223
IV. Summary Comment 229
References 229
Chapter 16. Oral Vaccines for Shigella 234
I. Bacillary Dysentery: Clinical Picture and Epidemiology 234
II. Pathogenesis and Molecular Biology of Shigella Infections 235
III. Immune Response in Shigellosis 236
IV. Vaccine Development 237
V. Conclusions 243
References 244
Chapter 17. Progress toward Live-Attenuated Cholera Vaccines 250
I. Introduction 250
II. Parenteral Cholera Vaccines 251
III. Oral Cholera Vaccines 252
IV. Infection-Derived Immunity 252
V. Killed Whole-Cell Oral Vaccines 252
VI. Live-Attenuated Oral Vaccines 253
VII. Nonrecombinant Live Oral Vaccines 253
VIII. Recombinant Live-Attenuated Vaccines 253
IX. CVD 103-HgR 256
X. A New Generation of Cholera Vaccines 256
References 259
Chapter 18. Oral Vaccines against Cholera and Enterotoxigenic Escherichia coli Diarrhea 262
I. Introduction 262
II. Mechanisms of Disease and Immunity 263
III. Oral Cholera Vaccines 265
IV. Oral B Subunit Whole-Cell ETEC Vaccine 268
V. Summary 271
References 272
Chapter 19. Mucosal Immunity to H. pylori: Implications for Vaccine Development 276
I . Introduction 276
II. Overview of H. pylori Infection 276
III. Gastric Immune and Inflammatory Responses to H. pylori Infection 277
IV. Why Develop a Vaccine for H. pylori? 280
V. Strategies for Successful Vaccination against H. pylori 280
VI. Experimental Evidence That Immunization Can Prevent and/or Cure Helicobacter Infection 281
VII. Future Challenges in Mucosal Vaccines for Helicobacter pylori 283
VIII. Summary 284
References 284
Chapter 20. Mucosal Immunity Induced by Oral Administration of Bacille Calmette—Guerin 290
I. General Background on Bacille Calmette—Guérin 290
II. History of Oral Bacille Calmette–Guérin Administration 291
III. Protective Mycobacterial Immune Responses 294
IV. Immunity Stimulated by Oral Bacille Calmette–Guérin Vaccination 295
V. Summary 297
References 297
Part VI: Mucosal Vaccines for Viral Diseases 302
Chapter 21. Polioviruses and Mucosal Vaccines 304
I. Introduction 304
II. Neurovirulence and Molecular Biology of Poliovirus 307
III . Virus Shedding and Revertants 308
IV. The Immune System and Poliovirus Vaccines 308
V. The Nature of Immune Responses to Polio Vaccines 311
VI. Polio Vaccines in Combinatio n with Other Vaccines 312
VII. Concluding Remarks 312
References 313
Chapter 22. The Rationale for a Mucosal Approach to the Prevention of Respiratory Syncytial Virus-Associated Pulmonary Disease 316
I. Introduction 316
II. Is There Immunity to RSV ? 317
III. Why Was Enhanced Illness Seen Following Inactivated Vaccine ? 317
IV. Role of Serum Antibody 318
V. Role of Mucosal Immunity 318
VI. Role of Cell-Mediated Immunity 318
VII. Mucosal Immunization 319
VIII. Summary 320
References 320
Chapter 23. Oral Immunization with Influenza Virus Vaccines 324
I. Introduction 324
II. Oral Immunization with Live Virus 324
III. Oral Immunization with Inactivated Virus 325
IV. Comment 329
References 329
Chapter 24. Parainfluenza Virus Vaccines 332
I. Introduction 332
II. Virology 332
III. Epidemiology 333
IV. Reinfection 334
V. Pathogenesis 334
VI. Antigenic Composition 334
VII. Immune Responses 335
VIII. Progress in Vaccine Development 335
IX. Development of Live-Attenuate d HPIV-3 Vaccine 336
X. Evaluation of Cold-Passaged Vaccine Strains in Animals 337
XI. Human Studies 337
XII. Molecular Characterization of the Candidate Vaccine Strain 339
XIII. Potential Use of Reverse Genetics in Vaccine Development 340
XIV. Concluding Remarks 340
References 340
Chapter 25. Development of a Mucosal Rotavirus Vaccine 346
I. Introduction 346
II. Immunologic Determinants of Protection against Rotavirus- Induced Gastroenteritis in Humans 347
III. Current Live Rotavirus Vaccines for Children 348
IV. Animal Models to Study Active Immunity 351
V. New Approaches to Vaccines for Children 357
VI. Summary and Conclusions 359
References 360
Chapter 26. Rotavirus Vaccine: The Clinical Experience with the Rhesus Rotavirus-Based Vaccines 366
I. Introduction : Importance of Rotavirus as a Cause of Diarrhea 366
II. Rotavirus Vaccine Development 366
III. Properties of Rotavirus Relevant to Vaccine Development 368
IV. Field Trials with Quadrivalent Vaccine 371
V. Other Modified Jennerian Approaches 373
VI. Non Jennerian Approach 374
VII. Cost Effectiveness of Rotavirus Vaccine 374
VIII. Summary 374
References 375
Chapter 27. Rectal and Genital Immunization with SIV/HIV 378
I. Introduction 378
II. Genito-Urinary and Rectal Epithelia 378
III. Epithelial Cells and Receptor s Involved in HIV Transmission 379
IV. Functional Biology of the Draining Lymph Nodes 380
V. HIV/SIV Target Cells in the Genital and Rectal Tracts 381
VI. Importance of Viral Variants in Sexual Transmission of HIV 382
VII. Genital and Intestinal Antibody Responses to SIV/HIV Infection 383
VIII. Genital and Rectal Cellular Responses to HIV/SIV Infection 384
IX. Routes of Immunization That Elicit Genito-Urinary and Rectal Immunity 385
X. Mucosal Immunity in Protection against Mucosal Challenge by Live SIV 386
References 387
Part VII: Site-Directed Mucosal Vaccines 394
Chapter 28. Mucosal Immunity in the Female Reproductive Tract : Effect of Sex Hormones on Immun e Recognition and Responses 396
I. Introduction 396
II. Mucosal Immunity in the Female Reproductive Tract 397
III. Sex Hormone Regulation of Mucosal Immunity in the Female Reproductive Tract 398
IV. Discussion 405
V. Conclusions 407
References 407
Chapter 29. Mucosal Immunity in the Urinary System 410
I. The Urinary Tract as a Model System for Studies of Mucosal Immunity 410
II. Urinary Tract Infection–Background 410
III. Mechanisms of Resistance to Bacterial Colonization 411
IV. Mucosal Inflammation 414
V. Specific Immunity in Urinary Tract Infection 416
VI. Prevention of Urinary Tract Infection 417
References 419
Chapter 30. Mucosal Immunity in the Ocular System 424
I. Introduction 424
II. Ocular Mucosal Immunobiology 424
III. Induction of Ocular Mucosal Immune Responses 427
IV. Targets for Vaccine Development 431
V. Summary 435
References 435
Chapter 31. Intranasal Immunization with Influenza Vaccine 446
I. Introduction 446
II. Protection against Influenza Virus Infection by Intranasal Immunization with the Adjuvant-Combined Vaccine 447
III. Immunological Basis of Protective Effect of Intranasal Immunization with Adjuvant-Combined Vaccine 451
IV. Usefulness of CT-B Containing a Trace Amount of CT as an Adjuvant for Intranasal Immunization with Vaccine 452
V. Perspective 453
References 454
Chapter 32. Mucosal Immunity and Periodontitis 458
I. Introduction 458
II. Humoral Immune Response in Periodontitis Patients 458
III. Prospects for a Vaccine 459
IV. Studies in Rodents 460
V. Studies in Nonhuman Primates 462
VI. Discussion 465
VII. Conclusions 467
References 467
Chapter 33. Mucosal Immunity of the Middle Ear 472
I. Introduction 472
II. Immunocompetent Cells in the Middle Ear Mucosa 472
III. Microorganisms in MEEs and Nasopharyngeal Secretions 473
IV. Systemic Immune Responses against Bacterial Antigen 473
V. Local Immune Response in the Middle Ear 474
VI. Immunoregulation in the Middle Ear 474
VII. Source of IgA Precursors in the Middle Ear 475
VIII. Mucosal Immunity in the Nasopharynx 476
IX. Prevention of Otitis Media by Mucosal Vaccination 476
References 477
Index 480