Vaccines by Peter PerlmanVaccines by Peter Perlman


byPeter PerlmanEditorHans Wigzell

Paperback | December 21, 2011

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The immune system is the only organ system in the body besides the central nervous systems endowed with memory. Both types of memories are specific and long-lasting, sometimes life long. This memory capacity of the immune system provides the basis for the most cost-efficient of all medical interventions, successful vaccinations against many common infectious diseases. Such a success requires the isolation of the infectious agent or toxic substance, methods to grow and/or purify the relevant antigen and change it into something innocuous whilst maintaining its immunogenicity. Whereas the early vaccines could only use the enhanced resistance against infectious disease as a measure of vaccine efficacy, most modern vaccines rely upon standardized laboratory tests accepted to parallel the in vivo protective capacity to confirm the quality and potency of the respective vaccine. We are presently experiencing an explosion in the development of new and/or improved vaccines. This is largely due to a parallel rapid expansion in our knowledge of the immune system and of the detailed molecular structure and function of microorganisms. Using this knowledge it is now possible to compose vaccines of new types where only certain molecules (or parts of molecules) derived from a pathogen are included, excluding other potentially harmful ones. Whereas earlier attenuated live vaccines were created by em­ pirical means such vaccines can now be created by molecularly defined inter­ ventions in the genome of the microorganism.
Title:VaccinesFormat:PaperbackDimensions:534 pages, 23.5 × 15.5 × 0.02 inPublished:December 21, 2011Publisher:Springer-Verlag/Sci-Tech/TradeLanguage:English

The following ISBNs are associated with this title:

ISBN - 10:3642641962

ISBN - 13:9783642641961

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Table of Contents

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.