Vaccines

1 Vaccines: Past, Present and Future.- A. Bacterial Vaccines: Past, Present and Future.- I. Past.- II. Present.- 1. Purified Sub-unit Vaccines.- a) Polysaccharides.- b) Protein-Polysaccharide Conjugate Vaccines.- 2. Purified Protein Sub-units.- 3. Genetically Modified Strains.- III. Future.- 1. Synthetic Peptides.- 2. Anti-idiotypes.- 3. Nucleic Acids.- 4. Live Recombinants.- 5. Multivalent Combinations.- 6. Slow-Release/Single-Dose Vaccines.- 7. Oral/Mucosal Delivery Systems.- B. Viral Vaccines.- I. Past.- II. Present.- III. Future.- C. Parasite Vaccines.- I. Past.- II. Present.- 1. Killed and Attenuated Vaccines.- 2. Peptide Vaccines.- 3. Vaccines Based on Expressed Parasite Proteins.- 4. Live Carriers.- 5. Other Approaches.- III. Future.- 1. DNA Vaccines.- 2. Adjuvants.- References.- 2 Immunology of Infection.- A. Introduction.- B. The Adaptive (Acquired) Immune Response.- C. The Cellular Immune System: T Cells.- I. MHC-Restricted Presentation of Epitopes to T Cells.- II. Conventional MHC-I or MHC-II Restricted TCR?ß T Cells.- III. Conventional MHC-Ia Restricted CD8+ TCR ?ß T Cells.- IV. Unconventional MHC-Ib Restricted CD8+ TCR?ß T Cells.- V. Unconventional Double-Negative (DN, CD4- CD8-), CDl-Restricted TCR ?ß T Cells.- VI. Unconventional CDl-Restricted CD4+ or DN NK1+ TCR?ß T Cells.- VII. TCRy?? T Cells.- D. Cytokines.- E. The Early Decision on the Type of Effector Functions that Prevail in an Immune Response.- F. The Humoral Immune System: B Cells.- G. T and B Cell Memory.- H. Mucosal Immunity.- I. Unsuccessful Induction of Specific Immune Responses.- J. Implications for Rational Vaccine Design.- References.- 3 DNA Vaccines: Immunogenicity and Preclinical Efficacy.- A. Overview.- B. Background.- C. Effectiveness of DNA Vaccines in Animal Models.- I. Miscellaneous.- II. Ferrets.- III. Nonhuman Primates.- D. Mucosal Immunization.- E. Delivery Systems and Adjuvants.- I. DNA Delivery.- II. DNA as Adjuvant.- F. Summary.- References.- 4 Antigen-Presentation Systems, Immunomodulators, and Immune Responses to Vaccines.- A. From Empirical Approaches to Rationally Selected Antigen-Presentation Systems and Immunomodulators for Vaccine-Mediated Protection Against Infectious Diseases.- B. What Are the Essential Parameters of Vaccine-Induced Effector Mechanisms?.- I. Antibody-Mediated Vaccine Responses.- II. Vaccine-Specific T Cell Responses.- 1. CD4 T Cell Vaccine Responses.- 2. Characteristics of Vaccine-Specific CD8 Cytotoxic Responses.- C. What Fundamental Immunological Mechanisms Can Be Modulated by Antigen-Delivery Systems and Immunomodulators?.- I. Modulation of Antigen Presentation to T/B Cells.- 1. Antigen Conformation.- 2. Antigen Persistence.- 3. Targeting of Professional Antigen-Presenting Cells.- II. Modulation of CD4 T Cell Responses.- III. Induction of CD8 T Cell Responses.- D. What Is the Effect of Specific Delivery Systems and Immunomodulators on Responses to Vaccine Antigens?.- I. Effect of Antigen-Delivery Systems.- 1. Live Bacterial and Viral Vectors.- a.) Bacterial Vectors.- b.) Viral Vectors.- 2. DNA Vaccines.- II. Effect of Particulate Substances on Vaccine Responses.- 1. Aluminum and Calcium Salts.- 2. Water and Oil Emulsions.- 3. Liposomes and Virosomes.- 4. Proteosomes.- 5. Micro- and Nanospheres of Biodegradable Polymers.- III. Effect of Immunomodulators that Can Be Incorporated into Antigen-Presentation Systems.- 1. Lipid A and Derivatives.- 2. Saponins (Quil A, QS21).- 3. Nonionic Block Copolymers.- 4. MDP and Derivatives.- 5. Cytokines and Interferons.- IV. Effect of Vaccine Formulations that Combine Antigen-Delivery Systems and Immunomodulatory Substances.- 1. Immune-Stimulating Complexes.- 2. W/O Emulsions with Built-In Immunomodulators.- 3. O/W Emulsions with Built-In Immunomodulators.- 4. Formulations Based on Liposomes with Built-in Immunomodulators.- E. How Can Vaccines Be Designed for Selected Target Populations with Variable Levels of Immunocompetence?.- I. Inducing Efficient Vaccine Responses in Early Life.- 1. Characteristics of Immune Responses in Early Life.- 2. Selecting Antigen-Presentation Systems/Immunomodulators for Use in Early Life.- a) Inducing Protective Antibody Responses in Infants and Neonates.- b) Inducing Strong TH1 and CTL Responses in Infants and Neonates.- c) Inducing Vaccine Responses in Presence of Maternal Antibodies.- II. Inducing Efficient Vaccine Responses in the Elderly.- III. Inducing Efficient Vaccine Responses in Immunodeficient Patients.- 1. Enhancing Vaccine Responses in Immunosuppressed Patients.- 2. Enhancing Vaccine Responses in HIV-1 Infected Patients.- F. Conclusions.- References.- 5 Vaccines Against Measles, Mumps, Rubella, and Varicella.- A. Introduction.- B. Measles Vaccine.- I. Safety and Efficacy of Live Measles Vaccine.- II. Epidemiological Consequences of Using Live Measles Vaccine.- III. New Kinds of Measles Vaccines.- IV. Remaining Problems in Using Measles Vaccine and Projected Future Developments.- C.) Mumps Vaccine.- I. Safety and Efficacy of Live Mumps Vaccine.- II. Epidemiological Consequences of Using Live Mumps Vaccine Use.- III. New Kinds of Mumps Vaccines.- IV. Remaining Problems in Using Mumps Vaccine and Projected Future Developments.- D. Rubella Vaccine.- I. Safety and Efficacy of Live Rubella Vaccine.- II. Epidemiological Consequences of Using Live Rubella Vaccine.- III. New Kinds of Rubella Vaccines.- IV. Remaining Problems in Using Rubella Vaccine and Projected Future Developments.- E. Varicella Vaccine.- I. Safety and Efficacy of Live Varicella Vaccine.- II. Epidemiological Consequences of Using Live Varicella Vaccine.- III. New Kinds of Varicella Vaccines.- IV. Remaining Problems in Using Varicella Vaccine and Priorities for the Future.- F. Epilogue.- References.- 6 Hepatitis and Polio Vaccines.- A. Introduction.- B. Hepatitis A Virus.- I. The Virus.- II. The Antigens.- III. The Disease.- IV. Immunity and Vaccines.- 1. Passive Immunization.- 2. Inactivated Whole Virus Vaccines.- 3. Live Attenuated Vaccines.- C. Hepatitis B Virus.- I. The Virus.- II. The Antigens.- 1. Envelope Proteins.- 2. Nucleocapsid Antigen.- III. The Disease.- IV. Immunity and Vaccines.- 1. Protective Immunity.- 2. Passive Immunization.- 3. Active Immunization.- a.) Targets.- b.) Current Vaccines: Plasma-Derived Vaccines.- c.) Recombinant Vaccines.- ?) HBsAg-Based.- ?) Pre-S Containing Vaccines.- ?) Alternative Vaccination Approaches.- ?) Therapeutic Vaccination?.- ?) Eradication of Hepatitis B?.- D. Hepatitis C Virus.- I. The Virus.- II. The Antigens.- III. The Disease.- IV. Vaccine Development.- E. Hepatitis E Virus.- I. The Virus.- II. The Antigens.- III. The Disease.- IV. Candidate Vaccines.- F. Poliovirus.- I. The Virus.- II. The Antigens.- III. The Disease.- IV. Inactivated Poliovaccines.- V. Oral Poliovaccines.- VI. Eradication of Poliomyelitis.- References.- 7 Herpes.- A. Herpesviridae.- B. Historical Background.- I. HSV.- II. CMV.- III. EBV.- C. The Glycoproteins.- D. Early Events of Human Herpes Virus Replication.- E. Latency.- F. Reactivation.- G. Clinical Infections.- I. HSV.- II. CMV.- III. EBV.- H. Immunology.- I. Therapeutic Vaccines.- I. Killed Vaccines.- II. Subunit Vaccines.- J. Prophylactic Vaccines.- I. HSV.- II. CMV.- 1. Live Vaccine.- 2. Subunit Vaccine.- III. EBV.- 1. Subunit Vaccines.- 2. Live Vaccines.- K. Conclusions.- References.- 8 Toxin-Based Vaccines (Diphtheria, Tetanus, Pertussis).- A. Introduction.- B. Diphtheria Toxin.- C. Tetanus Toxin.- D. Production, Effectiveness, and Problems of Conventional Diphtheria and Tetanus Vaccines.- I. Production and Detoxification of Diphtheria and Tetanus Toxoids.- II. Production and Detoxification of Purified Diphtheria and Tetanus Toxoids.- E. Future Prospects.- I. Engineered Live-Attenuated Strains.- II. Recombinant Molecules.- III. Mucosal Vaccination.- IV. CRM 197.- F. Diphtheria and Tetanus Toxoids as Carriers for Polysaccharide Vaccines.- G. Pertussis.- I. The Disease.- II. History of Acellular Vaccines.- III. Pertussis Toxin.- IV. Genetic Detoxification.- V. Acellular Vaccines Proposed.- VI. Clinical Trials.- VII. Other Clinical Studies.- References.- 9 Outer Membrane Protein Vaccines.- A. Introduction.- B. Neisseria gonorrhoeae.- I. Pili.- II. Outer Membrane Protein PI or Por.- III. PII or Opacity-Associated Proteins.- IV. Lipopolysaccharides.- V. Fe Limitation Inducible OMPs.- VI. Miscellaneous.- C. Neisseria meningitidis.- I. The Serogroup B Capsular Polysaccharide.- II. OMP Vaccines.- III. Opa and Opc.- IV. Pili.- V. Lipopolysaccharides.- VI. Fe Limitation Inducible OMPs.- VII. Miscellaneous.- D. Nontypable Haemophilus influenzae.- I. PI, P2, P4.- II. P6 and PCP.- III. Pili, Fimbriae, P5.- IV. High Molecular Weight Adhesins...- V. Lipopolysaccharide or Lipo-oligosaccharide.- VI. Fe Limitation Inducible OMPs.- VII. Miscellaneous.- E. Moraxella catarrhalis.- I. OMP CD, OMP E.- II. Pili/Fimbriae/High Molecular Weight OMPs.- III. Lipopolysaccharide or Lipo-oligosaccharide.- IV. Fe Limitation Inducible OMPs.- F. Animal Models.- References.- 10 Carbohydrate-Based Bacterial Vaccines.- A. Introduction.- B. The Hib Experience.- C. Meningococcal Polysaccharide and Conjugate Vaccines.- D. Pneumococcal Polysaccharide and Conjugate Vaccines.- I. Protein Carrier.- II. Polysaccharide Size.- III. Coupling Chemistry.- IV. Polysaccharide-Protein Ratio.- V. Adjuvant.- VI. Animal Models and Correlates of Protection.- VII. Clinical Trials of Pneumococcal Polysaccharide-Protein Conjugate Vaccines.- VIII. The Future of Pneumococcal Vaccines.- E. Salmonella, Shigella, and E. coli.- I. Salmonella: O-Antigen Specific Conjugates.- II. S. typhi: Vi-Antigen Specific Conjugates.- III. Shigella: O-Antigen Specific Conjugates.- IV. E. coli: O-Antigen Specific Conjugates.- References.- 11 Mycobacteria.- A. Introduction.- B. The Cellular Response to Mycobacteria.- I. Macrophage Interactions.- II. Recognition by CD4 T Cells.- III. The CD8 Response.- IV. Other Subsets.- C. Mycobacterial Antigens.- D. Protection Versus Disease.- E. Mycobacterial Vaccines.- I. Live Vaccines.- II. Subunit Vaccines.- III. DNA Vaccines.- F. Future Prospects.- References.- 12 Vaccines Against Diarrheal Diseases.- A. Introduction.- B. Overview of the Main Diarrrheal Pathogens.- I. Vibrio cholerae.- II. Enterotoxigenic Escherichia coli.- III. Shigella spp.- IV. Campylobacter jejuni.- V. Rotavirus.- C. Mechanisms of Disease and Immunity in Diarrheal Diseases.- I. Enterotoxins and Antitoxic Immunity.- II. Colonization and Antibacterial Immunity in Cholera and ETEC Infections.- III. Pathogenic and Immune Mechanisms in Shigella Infections.- IV. Protective Immunity in Rotavirus Infections.- D. Cholera Vaccines.- I. Oral Inactivated Vaccines.- II. Oral Live Vaccines.- III. Combined Vaccines Against O1 and O139 Cholera.- E. ETEC Vaccines.- I. Oral Inactivated Vaccines.- II. Oral Live Vaccines.- F. Shigella Vaccines.- I. Parenteral Vaccines.- II. Oral Live Vaccines.- G. Campylobacter jejuni Vaccines.- H. Rotavirus Vaccines.- References.- 13 Sexually Transmitted Diseases.- A. Introduction.- B. Special Challenges.- C. Gonorrhea.- I. Epidemiology.- II. Natural Infection.- III. Antigenic Variation.- IV. Whole-Cell Vaccines.- V. Subcomponent Vaccines.- 1. Porin.- 2. Lipo-oligosaccharides.- 3. Pili.- 4. Opacity Proteins.- 5. Transferrin Binding Proteins.- 6. IgA Protease.- VI. Prospects.- D. Chlamydia Infection.- I. Epidemiology.- II. Natural Infection.- III. Pathogenesis.- IV. Whole-Cell Vaccines.- V. Subcomponent Vaccines.- 1. Major Outer Membrane Protein.- 2. Heat Shock Protein 75 kDa.- VI. Prospects.- E. Genital Ulcers Caused by Haemophilus ducreyi.- I. Epidemiology.- II. Natural Infection.- III. Subcomponent Vaccines.- IV. Prospects.- F. Syphilis.- I. Epidemiology.- II. Natural Infection.- III. Antigenic Variation.- IV. Whole-Cell Vaccines.- V. Subcomponent Vaccines.- 1. Cardiolipin.- 2. Treponemal Proteins.- VI. Prospects.- G. Human Genital Papilloma Virus Infection.- I. Epidemiology.- II. Natural Infection.- III. Whole-Viral Vaccines.- IV. Subcomponent Vaccines.- V. Prospects.- H. Herpes Simplex Infection.- I. Epidemiology.- II. Natural Infection.- III. Whole-Viral Vaccines.- IV. Subcomponent Vaccines.- V. Prospects.- I. Conclusion.- References.- 14 Designing a Vaccine Against HIV.- A. Perspective.- I. The Need for a Vaccine.- II. The First Decade: 1985-1995.- III. New Paradigms.- IV. What Should the Vaccine Do?.- V. Design Considerations.- B. The Role of Antibody.- I. Passive Transfer.- II. Does HIV Have Serotypes?.- III. Do Coreceptor Families of HIV Represent Serotypes?.- IV. Design Considerations.- 1. The Ideal Immunogen.- 2. Obstacles to Inducing a Broad Response.- 3. Human Monoclonal Antibodies as Clues.- 4. Is Neutralization Required for Protection?.- C. The Role of Cytotoxic T-Cells.- I. Evidence from Vaccination and Challenge.- II. Evidence from Infection.- III. Addressing the Heterogeneity of HIV.- IV. Design Considerations.- D. Other T-Cell Activities.- E. Mucosal Immunity.- F. Vaccine Approaches.- I. Live-Attenuated Vaccine.- II. Whole, Inactivated Virus.- III. Recombinant Vectors.- IV. Plasmid Immunization.- V. Subunit Proteins and Peptides.- VI. Combinations.- G. Prospectus.- I. Design Considerations.- II. Evaluation Considerations.- References.- 15 An Overview of Malaria Vaccine Development Efforts.- A. Epidemiology.- B. The Parasite.- C. Approaches to Malaria Vaccine Development: Preventing Erythrocytic Stage Infection or Reducing Morbidity and Mortality Without Preventing Infection.- D. Preerythrocytic Stage Vaccines.- I. Preventing Sporozoite Invasion of Hepatocytes.- II. Attacking Infected Hepatocytes.- E. Erythrocytic Stage Vaccines: Reducing Parasite Burden and Blocking Pathogenesis.- I. Approaches to Reducing Parasite Burden.- 1. Preventing Merozoite Invasion of Erythrocytes.- 2. Attacking Infected Erythrocytes.- II. Antiparasite Immune Mechanisms that Contribute to Parasite Reduction.- 1. Reduction in Parasite Burden: The Direct Effects of Antibodies.- 2. Reduction in Parasite Burden: The Role of Cellular Mechanisms Through Direct Effects of Cytokines and Other Bioactive Molecules.- a) The Role of CD4+ T Cells.- b) The Role of ?/? T Cells.- c) The Role of Cytokines.- III. Data Supporting Reduction in Parasite Burden and the Status of Experimental Erythrocytic Stage Vaccines Designed To Reduce Parasite Burden.- 1. MSP1.- 2. MSP2.- 3. AMA1.- 4. EBA-175.- 5. SERA.- 6. RESA.- 7. Synthetic SPf66 Vaccine.- IV. Blocking Pathogenesis.- 1. Inhibiting Adherence of Infected Erythrocytes to Endothelial Cells.- 2. Inhibiting Adherence of Infected Erythrocytes to Other Erythrocytes (Rosetting).- 3. Inhibiting Malaria Toxins.- F. Transmission Blocking Vaccines.- I. Gamete and Early Zygote Surface Target Antigens.- II. Late Zygote Ookinete Surface Target Antigens.- III. Ookinete Secreted and Mosquito Derived Target Antigens.- IV. Progress Towards a Transmission Blocking Vaccine.- G. Conclusions.- References.- 16 Antifertility Vaccines.- A. Introduction.- B. Current Status of Vaccine Development.- I. Antisperm Vaccines.- II. Ovum Antigens.- III. Antihormone Vaccines.- 1. Gonadotropin-Releasing Hormone.- 2. Follicle-Stimulating Hormone.- 3. Human Chorionic Gonadotropin.- C. Problems and Prospects.- References.- 17 Cancer Vaccines.- A. Introduction.- B. Tumor Antigens.- I. Recognition by Antibodies.- II. Recognition by T Lymphocytes.- III. Tumor Peptides as T Cell Targets.- IV. Antigen Presentation.- C. Types of Tumor Vaccines.- D. Downregulatory Mechanisms.- E. Conclusions and Outlook.- References.- 18 Prevention of Autoimmunity.- A. Overview of Autoimmune Diseases.- B. Autoreactive T Cells.- C. Antigen-Specific Therapy.- I. Altered Peptide Ligands.- II. Oral Tolerance.- 1. Mechanisms of Oral Tolerance.- 2. Bystander Suppression.- 3 Modulation of Oral Tolerance.- III. Nasal and Aerosol Mucosal Tolerance.- IV. Treatment of Autoimmune Diseases in Animals.- 1. Experimental Autoimmune Encephalomyelitis.- 2. Arthritis.- 3. Uveitis.- 4. Myasthenia Gravis.- 5. Diabetes.- 6. Transplantation and Other Models.- V. Treatment of Autoimmune Diseases in Humans.- D.Future Directions.- References.- 19 Vaccines Against Allergies.- A. Introduction.- B. The Allergic Immune Response.- C. Traditional Immunotherapy.- I. Modified Allergens or Allergen Extracts.- II. Oral Administration of Recombinant Allergens or Allergen Extracts.- III. Peptide Vaccines.- IV. Cytokine Agonists and Antagonists.- V. Low Molecular Weight Compounds Interfering with the Interaction Between IgE and its High-Affinity Receptor.- VI. Depletion of Plasma and Mast Cell Bound IgE by Treatment with Monoclonal Anti-IgE Antibodies.- VII. Induction of a Strong Anti-IgE Response by Vaccination.- D. Conclusions.- References.