BOOK
Vaccines E-Book
Stanley A. Plotkin | Walter Orenstein | Paul A. Offit | Kathryn M. Edwards
(2017)
Additional Information
Book Details
Abstract
From the development of each vaccine to its use in reducing disease, Plotkin’s Vaccines, 7th Edition, provides the expert information you need to provide optimal care to your patients. This award-winning text offers a complete understanding of each disease, as well as the latest knowledge of both existing vaccines and those currently in research and development. Described by Bill Gates as "an indispensable guide to the enhancement of the well-being of our world," Plotkin’s Vaccines is a must-have reference for current, authoritative information in this fast-moving field.
- Includes complete information for each disease, including clinical characteristics, microbiology, pathogenesis, diagnosis, and treatment, epidemiology, and public health and regulatory issues – plus complete information for each vaccine, including its stability, immunogenicity, efficacy, duration of immunity, adverse events, indications, contraindications, precautions, administration with other vaccines, and disease-control strategies.
- Analyzes the cost-benefit and cost-effectiveness of different vaccine options.
- Helps you clearly visualize concepts and objective data through an abundance of tables and figures.
- Covers the new oral cholera and zoster vaccines, as well as newly licensed meningococcal group B vaccines and a newly licensed dengue vaccine.
- Brings you up to date on successful human trials of Ebola vaccines, an enterovirus 71 vaccine licensed in China, and new recommendations and changes to polio vaccines.
- Features a new chapter on maternal immunization.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | cover | ||
| Inside Front Cover | ifc1 | ||
| Half title page | i | ||
| Legends | ii | ||
| Plotkin's Vaccines | iii | ||
| Copyright Page | iv | ||
| Table Of Contents | v | ||
| Foreword | viii | ||
| Preface to the First Edition | x | ||
| Preface to the Seventh Edition | xi | ||
| Contributors | xii | ||
| Acknowledgments | xx | ||
| Dedication | xxi | ||
| 1 General Aspects of Vaccination | 1 | ||
| 1 A Short History of Vaccination | 1 | ||
| Early Developments | 1 | ||
| Louis Pasteur and the Age of Vaccination | 3 | ||
| First Half of the 20th Century | 7 | ||
| Second Half of the 20th Century to the Present | 10 | ||
| Recombinant Protein Vaccines | 14 | ||
| References | 15.e1 | ||
| 2 Vaccine Immunology | 16 | ||
| How Do Vaccines Mediate Protection? | 16 | ||
| What Are the Main Effectors of Vaccine Responses? | 16 | ||
| From Innate to Adaptive Immunity Activation: The First Steps After Immunization | 20 | ||
| Vaccine Antibody Responses | 23 | ||
| How Are Primary Antibody Responses Elicited? | 23 | ||
| T-Dependent Responses to Protein Antigens | 23 | ||
| The Extrafollicular Reaction. | 23 | ||
| The Germinal Center Reaction. | 23 | ||
| T-Independent Responses to Polysaccharide Antigens | 23 | ||
| What Are the Determinants of Primary Vaccine Antibody Responses? | 25 | ||
| What Controls the Persistence of Vaccine Antibody Responses? | 26 | ||
| What Are the Hallmarks of B-Cell Memory Responses? | 26 | ||
| What Are the Determinants of B-Cell Memory Responses? | 27 | ||
| Immune Memory and Vaccine-Induced Protection: A Race Between Reactivation and Microbial Invasion? | 28 | ||
| T-Cell Vaccine Responses | 29 | ||
| How Do Vaccines Induce CD4+ and CD8+ T-Cell Responses? | 29 | ||
| What Are the Determinants of Vaccine-Induced T-Cell Memory? | 31 | ||
| How Specific Are Vaccine Immune Responses? | 31 | ||
| Vaccine Responses at the Extremes of Age | 32 | ||
| The Challenges of Neonatal and Early Life Immunization. | 32 | ||
| Age-Associated Changes in Vaccine Responses. | 34 | ||
| References | 34.e1 | ||
| 3 Correlates of Protection | 35 | ||
| Principles of Protection | 35 | ||
| Principle 1: Protection Must Be Defined in Relation to Specific Phenomena | 35 | ||
| Principle 2: The Mechanism of Protection by Vaccination Is Not Necessarily the Same Mechanism as Recovery From Infection | 35 | ||
| Principle 3: A Large Challenge Dose Can Overcome Immunity | 36 | ||
| Principle 4: Most Current Vaccines Protect Through Antibodies | 36 | ||
| Principle 5: Correlates May Be Relative | 36 | ||
| Principle 6: Antibodies Must Be Functional | 37 | ||
| Principle 7: T-Cell Responses May Be Correlates | 37 | ||
| Principle 8: More Than One Factor May Protect as Cocorrelates | 37 | ||
| Principle 9: Memory May Be a Mechanistic Correlate of Protection | 38 | ||
| Principle 10: There Are Convenient Nonmechanistic Correlates | 38 | ||
| Statistical Issues in Developing Immune Correlates of Protection | 38 | ||
| Complexity of Correlates | 40 | ||
| Conclusions | 40 | ||
| References | 40.e1 | ||
| 4 The Vaccine Industry | 41 | ||
| Vaccine Development | 41 | ||
| Role of Partners | 43 | ||
| Funding Sources for Vaccine Research and Development | 46 | ||
| India | 47 | ||
| China | 48 | ||
| Brazil | 49 | ||
| Summary | 49 | ||
| Pricing of Vaccines | 49 | ||
| Vaccine Market | 50 | ||
| Acknowledgments | 50 | ||
| References | 50.e1 | ||
| 5 Vaccine Manufacturing | 51 | ||
| Manufacturing Basics | 51 | ||
| Examples of Vaccine Production | 54 | ||
| Inactivated Virus (Influenza) | 54 | ||
| Recombinant Protein (Hepatitis B) | 55 | ||
| Conjugate Vaccine (Haemophilus influenzae Type B) | 56 | ||
| Live Attenuated Vaccine (Measles) | 57 | ||
| Virus-Like Particle–Based Vaccines | 57 | ||
| Product Development | 58 | ||
| Industry’s Response to New Challenges | 58 | ||
| Manufacturing Flexibility in Scale-Up: New Trends in Single Use | 58 | ||
| Promise and Challenges of Distributed Manufacturing | 58 | ||
| Future Challenges in Polio Vaccine Manufacturing | 59 | ||
| Prime-Boost Vaccines | 59 | ||
| References | 60.e1 | ||
| 6 Evolution of Adjuvants Across the Centuries | 61 | ||
| Chance and Necessity: the Discovery of Adjuvants | 61 | ||
| A Turning Point: Better Understanding of Immunology and Its Impact on the Development of Adjuvants | 61 | ||
| Defining Adjuvants: Classification and Evaluation | 63 | ||
| A Categorization of Adjuvants Based on Mechanism of Action | 63 | ||
| Aluminum Salt Adjuvants | 63 | ||
| Structure and Properties. | 63 | ||
| Effect of Freezing. | 64 | ||
| Adsorption Mechanisms. | 66 | ||
| Mechanisms of Action of Aluminum Salt Adjuvants. | 66 | ||
| Safety of Aluminum-Containing Vaccines. | 66 | ||
| Water-in-Oil Emulsions | 66 | ||
| Oil-in-Water Emulsions | 67 | ||
| Adjuvant Effect of Oil-in-Water Emulsions on Naïve Versus Primed Persons. | 67 | ||
| Enhancing the Breadth of the Immune Response. | 68 | ||
| Mode of Action. | 68 | ||
| Safety of Squalene-Containing Oil-in-Water Emulsions. | 68 | ||
| Other Oil Alternatives for Squalene. | 69 | ||
| Toll-Like Receptor Agonists | 69 | ||
| TLR4 Agonists | 69 | ||
| Mechanism of Action of TLR4 Agonists. | 69 | ||
| Species Specificity of TLR4 Receptor. | 69 | ||
| Other TLR4 Agonists. | 69 | ||
| Formulation Challenges. | 71 | ||
| Safety of TLR4 Agonists. | 71 | ||
| TLR9 Agonists | 71 | ||
| Other TLR9 Agonists. | 71 | ||
| Other Toll-Like Receptor Ligands | 72 | ||
| Other Adjuvants | 72 | ||
| Saponins. | 72 | ||
| Virosomes. | 72 | ||
| Polyelectrolytes and Polycations. | 73 | ||
| Mucosal Adjuvants. | 73 | ||
| Future Directions | 73 | ||
| Acknowledgment | 74 | ||
| References | 74.e1 | ||
| 7 Vaccine Additives and Manufacturing Residuals in Vaccines Licensed in the United States | 75 | ||
| Vaccine Additives | 75 | ||
| Preservatives | 75 | ||
| Adjuvants | 78 | ||
| Stabilizers | 78 | ||
| Manufacturing Residuals | 80 | ||
| Inactivation Residuals | 80 | ||
| Residual Cell Culture Materials | 81 | ||
| Antibiotics | 81 | ||
| Sensitizing Substances | 81 | ||
| Bacterial and Cellular Residuals | 82 | ||
| Adventitious Agents | 83 | ||
| Transmissible Spongiform Encephalopathy Agents | 83 | ||
| Summary | 83 | ||
| References | 83.e1 | ||
| 8 Passive Immunization | 84 | ||
| Maternal Antibodies: The Original Passive Immunotherapy | 84 | ||
| Critical Parameters for Passive Immunotherapy | 86 | ||
| Passive Immunity Against Respiratory and Enteric Pathogens | 92 | ||
| Passive Immunization: A Paradigm Shift in Progress? | 93 | ||
| Future of Passive Immunization | 94 | ||
| References | 95.e1 | ||
| 9 General Immunization Practices | 96 | ||
| Vaccine Storage and Handling | 96 | ||
| Vaccine Administration | 96 | ||
| Infection Control and Sterile Injection Technique | 96 | ||
| Route of Administration | 97 | ||
| Subcutaneous Injections | 97 | ||
| Intramuscular Injections | 97 | ||
| Vaccinating Persons With Bleeding Disorders and Persons Receiving Anticoagulant Therapy | 99 | ||
| Intradermal Injections | 99 | ||
| Oral Administration | 99 | ||
| Intranasal Route | 99 | ||
| Needle-Shielding/Needle-Free Devices | 99 | ||
| Jet Injectors | 99 | ||
| Alleviation of Pain and Discomfort Associated With Vaccination | 100 | ||
| Ages for Administration of Immunobiologics | 100 | ||
| Spacing of Vaccine Doses | 100 | ||
| Spacing of Multiple Doses of the Same Vaccine | 100 | ||
| Spacing of Different Vaccines | 106 | ||
| Simultaneous Administration of Different Vaccines | 107 | ||
| Interference by Immunoglobulins | 108 | ||
| Interference With Live Virus Vaccines | 108 | ||
| Interference With Inactivated and Component Vaccines | 108 | ||
| Recommendations for Spacing Administration of Vaccines and Immunoglobulins | 108 | ||
| Interchangeability of Vaccines From Different Manufacturers | 109 | ||
| Hypersensitivity to Vaccine Components | 111 | ||
| Types of Reactions | 111 | ||
| Vaccine Components Causing Hypersensitivity | 111 | ||
| Proteins | 111 | ||
| Latex | 111 | ||
| Antimicrobial Agents | 112 | ||
| Thimerosal | 112 | ||
| Management of Acute Vaccine Adverse Reactions | 112 | ||
| Special Considerations | 112 | ||
| Vaccination of Preterm Infants | 112 | ||
| Breastfeeding and Immunization | 113 | ||
| Vaccination During Pregnancy | 113 | ||
| Vaccination of Household Contacts | 114 | ||
| Vaccines Received Outside the United States | 114 | ||
| Vaccination of Persons With A Personal or Family History of Seizures | 115 | ||
| Vaccination During Acute Illness | 115 | ||
| Contraindications to and Precautions Regarding Vaccination | 116 | ||
| References | 120.e1 | ||
| 2 Licensed Vaccines and Vaccines in Development | 121 | ||
| 10 Adenovirus Vaccines | 121 | ||
| History of Disease | 121 | ||
| Why the Disease Is Important | 121 | ||
| Background | 121 | ||
| Clinical Description | 121 | ||
| Endemic Respiratory Adenovirus in Children | 121 | ||
| Epidemic Respiratory Adenovirus in Children | 121 | ||
| Acute Respiratory Disease of Military Recruits | 121 | ||
| Pharyngoconjunctival Fever | 122 | ||
| Epidemic Keratoconjunctivitis | 122 | ||
| Hemorrhagic Cystitis | 122 | ||
| Gastroenteritis | 122 | ||
| Rare Acute Manifestations | 122 | ||
| Complications | 123 | ||
| Adenovirus Infections in Immunocompromised Patients | 123 | ||
| Chronic Diseases Caused by Adenoviruses | 123 | ||
| Virology | 123 | ||
| Pathogenesis as It Relates to Prevention | 124 | ||
| Laboratory Diagnosis | 125 | ||
| Specimen Collection. | 125 | ||
| Cell Culture. | 125 | ||
| Direct Visualization of Virus Particles | 125 | ||
| Antigen Assays. | 125 | ||
| Molecular Assays. | 126 | ||
| Adenovirus Typing Assays. | 126 | ||
| Serological Assays. | 126 | ||
| Treatment and Prevention With Antimicrobials | 126 | ||
| Epidemiology | 127 | ||
| Incidence and Prevalence Data | 127 | ||
| High-Risk Groups | 127 | ||
| Modes of Transmission and Reservoirs of Infection | 127 | ||
| Significance as a Health Burden | 127 | ||
| Passive Immunization | 128 | ||
| Active Immunization | 128 | ||
| Constituents Including Antibiotics, Preservative, Adjuvants, Etc. | 130 | ||
| Preparations Available, Including Combinations | 130 | ||
| Dosage and Route: Intramuscular, Subcutaneous, and Oral | 131 | ||
| Vaccine Stability | 131 | ||
| Immunogenicity of Vaccine | 131 | ||
| Humoral Responses | 131 | ||
| Cellular Responses | 131 | ||
| Correlates of Protection | 131 | ||
| Special Groups (e.g., Immunosuppressed) | 131 | ||
| Efficacy and Effectiveness of Vaccine | 131 | ||
| Duration of Immunity and Protection, Including Description of Reinfection, If Any | 131 | ||
| Safety | 131 | ||
| Common Adverse Events | 131 | ||
| Rare Adverse Events | 132 | ||
| Immunocompromised Recipients | 132 | ||
| Pregnancy | 132 | ||
| Spread to Contacts | 132 | ||
| Indications for Vaccine—Who and Why | 132 | ||
| Contraindications and Precautions | 132 | ||
| Public Health Considerations | 132 | ||
| Epidemiologic Effects of Vaccination, Including Herd and Contact Immunity | 132 | ||
| Disease Control Strategies | 133 | ||
| Cost-to-Benefit Information | 133 | ||
| Future Vaccines | 133 | ||
| Subunit Vaccine | 133 | ||
| Recombinant Vaccines | 133 | ||
| Acknowledgments | 133 | ||
| References | 133.e1 | ||
| 11 Anthrax Vaccines* | 134 | ||
| Background | 135 | ||
| Clinical Description | 135 | ||
| Cutaneous Anthrax | 135 | ||
| Inhalational Anthrax | 135 | ||
| Gastrointestinal Anthrax | 136 | ||
| Bacteriology | 136 | ||
| Pathogenesis | 136 | ||
| Diagnosis | 138 | ||
| Treatment and Prevention With Antibiotics | 138 | ||
| Epidemiology | 138 | ||
| Passive Immunization | 139 | ||
| Active Immunization | 141 | ||
| History of Vaccine Development | 141 | ||
| Description of Vaccines | 141 | ||
| Immunogenicity of Anthrax Vaccine Adsorbed Vaccine Produced in the United States | 142 | ||
| Cellular Responses | 142 | ||
| Correlates of Protection | 142 | ||
| Efficacy of Vaccine | 143 | ||
| Duration of Immunity | 143 | ||
| Postexposure Prophylaxis With Vaccination | 143 | ||
| Vaccine Safety | 145 | ||
| Common Adverse Effects | 145 | ||
| Rare Adverse Effects | 145 | ||
| Indications for Vaccination | 146 | ||
| Contraindications and Precautions | 147 | ||
| Public Health Considerations | 147 | ||
| Future Vaccines | 147 | ||
| References | 148.e1 | ||
| 12 Biodefense and Special Pathogen Vaccines | 149 | ||
| Limited-Use Vaccines Against Viral Diseases | 151 | ||
| Alphaviruses | 151 | ||
| Venezuelan Equine Encephalitis Virus | 151 | ||
| Western Equine Encephalitis Virus | 152 | ||
| Eastern Equine Encephalitis Virus | 153 | ||
| Chikungunya Virus | 153 | ||
| Ross River Virus | 154 | ||
| Bunyaviruses | 154 | ||
| Rift Valley Fever Virus | 154 | ||
| Hantaviruses | 155 | ||
| West Nile Virus | 156 | ||
| Arenaviruses | 156 | ||
| Junin Virus | 156 | ||
| Lassa Virus | 156 | ||
| Middle East Respiratory Syndrome Virus | 157 | ||
| Limited-Use Vaccines Against Bacterial Diseases | 157 | ||
| Q Fever | 157 | ||
| Tularemia | 158 | ||
| Brucellosis | 158 | ||
| Pseudomonas | 159 | ||
| Helicobacter pylori | 159 | ||
| Botulism | 159 | ||
| Clostridium difficile | 160 | ||
| Acknowledgments | 160 | ||
| References | 160.e1 | ||
| 13 Cancer Vaccines | 161 | ||
| The Concept of Cancer Vaccines Is Anchored in Classical Vaccinology | 161 | ||
| Understanding Tumor Immunobiology Is Key to Designing Efficacious Cancer Vaccines | 161 | ||
| Tumor Antigens | 161 | ||
| Antigen Presentation and T-Cell Proliferation | 162 | ||
| Tumor-Derived Exosomes | 162 | ||
| Immunogenic and Nonimmunogenic Cell Death | 163 | ||
| Chemotherapy-Induced Immunogenic Apoptosis | 163 | ||
| T-Cell Differentiation | 163 | ||
| Maintenance of Effector Cells | 163 | ||
| T-Cell Trafficking to Tumors | 163 | ||
| All Hurdles Facing Cancer Vaccines Need to Be Systematically Addressed | 163 | ||
| T-Cell–Negative Regulation by Antigen-Presenting, Stromal, and Tumor Cells | 164 | ||
| Myeloid-Derived Suppressor Cell T-Cell Inhibition | 164 | ||
| Regulatory T-Cell Immune Suppression | 164 | ||
| Additional Regulatory Immune Cells | 166 | ||
| Immune-Tolerant T Cells of Low Avidity | 166 | ||
| Immune Deviation: Th2 Polarization | 166 | ||
| Intrinsic Resistance of the Tumor Target to T Cells | 166 | ||
| Suboptimal Immunologic Monitoring | 167 | ||
| Cancer Vaccine Platform Technologies Continue to Undergo Significant Diversification | 167 | ||
| Cellular Vaccines—Tumor Cells | 168 | ||
| Cellular Vaccines—Dendritic Cells | 169 | ||
| Peptide Vaccines | 170 | ||
| Protein-Based Vaccines | 170 | ||
| Carbohydrate Vaccines | 171 | ||
| DNA Vaccines | 171 | ||
| Microbial Vaccines | 172 | ||
| RNA-Based Vaccines | 172 | ||
| Oncolytic Virus Vaccines | 173 | ||
| Vaccines in Clinical Development for Specific Cancers | 173 | ||
| Vaccines in Development for Specific Tumor Types | 173 | ||
| Prostate Cancer | 173 | ||
| Breast Cancer | 174 | ||
| Lung Cancer | 174 | ||
| Melanoma | 175 | ||
| Pancreatic Cancer | 175 | ||
| Colorectal Cancer | 175 | ||
| Renal Cell Carcinoma | 176 | ||
| Advancement to Late-Stage Development Is Not a Success Predictor for Cancer Vaccines | 176 | ||
| Cancer Vaccines Have Substantial Potential but Need Further Optimization and Repositioning Within the Therapeutic Armamentarium Against Cancer | 179 | ||
| Enhancing Vaccine Activity by Combination With Immune Modulators or Other Immunotherapies | 180 | ||
| Vaccines and Checkpoint Inhibitors | 180 | ||
| Vaccines and Cellular Therapy | 182 | ||
| References | 184.e1 | ||
| 14 Cholera Vaccines | 185 | ||
| History of Disease | 185 | ||
| Why the Disease Is Important | 185 | ||
| Clinical Description and Complications | 185 | ||
| Bacteriology | 185 | ||
| Pathogenesis as It Relates to Prevention | 186 | ||
| Modes of Transmission | 186 | ||
| Diagnosis | 186 | ||
| Case Management | 187 | ||
| Epidemiology | 187 | ||
| Incidence | 187 | ||
| Risk Groups | 188 | ||
| Reservoirs of Infection | 188 | ||
| Significance as a Public Health Problem | 188 | ||
| Passive Immunization | 189 | ||
| Active Immunization | 189 | ||
| History of Vaccine Development | 189 | ||
| Immunization With Modern, Licensed Oral Vaccines | 189 | ||
| Killed Whole-Cell Vaccine Plus Cholera Toxin B Subunit | 190 | ||
| Constituents of the Vaccine. | 190 | ||
| Manufacture of the Vaccine. | 190 | ||
| Producer. | 190 | ||
| Dosage and Route. | 190 | ||
| Availability in Combinations. | 191 | ||
| Vaccine Stability. | 191 | ||
| Immunogenicity and Immune Correlates of Protection. | 191 | ||
| Excretion and Transmissibility. | 191 | ||
| Duration of Immunity and Protection. | 191 | ||
| Postexposure Prophylaxis. | 192 | ||
| Safety. | 192 | ||
| Indications. | 192 | ||
| Contraindications and Precautions. | 192 | ||
| Reformulated Killed Whole Cell–Only Bivalent Vaccine | 192 | ||
| Constituents of the Vaccine. | 192 | ||
| Manufacture of the Vaccine. | 192 | ||
| Producers and Trade Names. | 192 | ||
| Dosage and Route. | 192 | ||
| Availability in Combinations. | 192 | ||
| Vaccine Stability. | 192 | ||
| Immunogenicity and Immune Correlates of Protection. | 192 | ||
| Excretion and Transmissibility. | 193 | ||
| Duration of Immunity and Protection. | 193 | ||
| Postexposure Prophylaxis. | 193 | ||
| Safety. | 193 | ||
| Indications. | 193 | ||
| Contraindications and Precautions. | 193 | ||
| Live Oral Vaccine (CVD103-HgR) | 193 | ||
| Constituents of the Vaccine. | 194 | ||
| Manufacture of the Vaccine. | 194 | ||
| Producers and Trade Names. | 194 | ||
| Dosage and Route. | 194 | ||
| Availability in Combinations. | 194 | ||
| Vaccine Stability. | 194 | ||
| Immunogenicity and Immune Correlates of Protection. | 194 | ||
| Excretion and Transmissibility. | 194 | ||
| Duration of Immunity and Protection. | 194 | ||
| Postexposure Prophylaxis. | 194 | ||
| Safety. | 194 | ||
| Indications. | 194 | ||
| Contraindications. | 194 | ||
| Public Health Considerations | 194 | ||
| Epidemiologic Setting | 194 | ||
| Vaccine Impact | 195 | ||
| Feasibility and Cost Effectiveness | 196 | ||
| Travelers | 196 | ||
| World Health Organization Oral Cholera Vaccine Stockpile | 196 | ||
| Future Vaccines | 196 | ||
| New Killed Whole Cell–Only Cholera Vaccines | 196 | ||
| Live Oral Vaccines Against O1 Serogroup Cholera | 197 | ||
| Live Oral Vaccines Against 0139 Serogroup Cholera | 197 | ||
| Parenteral Vaccines | 197 | ||
| Acknowledgment | 197 | ||
| References | 197.e1 | ||
| 15 Combination Vaccines | 198 | ||
| Terminology | 198 | ||
| Principles of Combined Vaccines | 198 | ||
| Simultaneous Vaccines | 198 | ||
| Combination Vaccines and the Immune System | 204 | ||
| Carrier-Induced Epitopic Modification | 204 | ||
| Other Issues Affecting Immune Responses | 205 | ||
| Other Impediments to the Development of Combination Vaccines | 205 | ||
| Licensure of Combination Vaccines | 205 | ||
| Evaluating Effectiveness | 206 | ||
| Evaluating Safety | 206 | ||
| Question of Multiple Antigens and Immune Overload | 206 | ||
| Postmarketing Surveillance | 206 | ||
| Combinations Based on DTwP (or Its Components) | 207 | ||
| DTwP/IPV, DT/IPV, and Td/IPV | 207 | ||
| DTwP/Hib (With or Without IPV) | 207 | ||
| DTwP/HepB (With or Without Hib) | 209 | ||
| Combinations Based on Acellular Pertussis Vaccine | 209 | ||
| 3 New Technologies | 1283 | ||
| 66 Technologies for Making New Vaccines | 1283 | ||
| Active Vaccines | 1283 | ||
| Live Vaccines | 1287 | ||
| Classic Strategy for Viral Targets | 1287 | ||
| Attenuation in Cell Culture. | 1287 | ||
| Variants From Other Species. | 1288 | ||
| Reassorted Genomes. | 1288 | ||
| Temperature-Sensitive Mutants. | 1288 | ||
| Recombinant Technology-Based Strategies for Viral Targets | 1288 | ||
| DNA Viruses | 1289 | ||
| RNA Viruses | 1289 | ||
| Classic Versus Recombinant Technology-Based Strategies for Bacterial Targets | 1289 | ||
| Serial Passage | 1289 | ||
| Mutagenesis | 1290 | ||
| Recombinant Bacteria | 1290 | ||
| Recombinant Bacterial Vectors | 1290 | ||
| Dendritic Cells as Autologous Vaccines | 1290 | ||
| Inactivated Vaccines | 1290 | ||
| Whole Pathogen | 1291 | ||
| Inactivated Bacteria. | 1291 | ||
| Inactivated Virus. | 1291 | ||
| Whole Human Cells | 1291 | ||
| Protein-Based/Subunit Vaccines | 1291 | ||
| Viral Targets for Protein-Based Approaches. | 1292 | ||
| Bacterial Targets for Protein-Based Approaches. | 1292 | ||
| Tumor Cells. | 1292 | ||
| Chemical Inactivation. | 1292 | ||
| Genetic Inactivation. | 1292 | ||
| Recombinant Polypeptides. | 1292 | ||
| Particle-Based Vaccines. | 1292 | ||
| Natural Protein Sequences. | 1292 | ||
| Fusion Proteins. | 1293 | ||
| Noninfectious Disease. | 1293 | ||
| Custom Design. | 1293 | ||
| DNA Shuffling. | 1293 | ||
| Host Cell Expression Systems. | 1294 | ||
| Peptide Based | 1294 | ||
| B-Cell Epitopes | 1294 | ||
| Aggregate. | 1294 | ||
| Fusion Protein. | 1294 | ||
| Fusion Peptide. | 1294 | ||
| Conjugate. | 1295 | ||
| Complex Peptide. | 1295 | ||
| Mimotopes. | 1295 | ||
| T-Cell Epitopes. | 1295 | ||
| Cytotoxic T-Lymphocyte Epitopes. | 1295 | ||
| T-Cell Activation. | 1295 | ||
| T-Cell Receptor. | 1295 | ||
| Carbohydrate and Polysaccharide Based. | 1295 | ||
| Polysaccharide. | 1295 | ||
| Conjugated Polysaccharide. | 1295 | ||
| Other Carbohydrate. | 1296 | ||
| Other | 1296 | ||
| Nucleic Acid–Based Vaccines | 1296 | ||
| Naked DNA | 1296 | ||
| Facilitated DNA | 1297 | ||
| Delivery. | 1297 | ||
| Composition. | 1297 | ||
| Viral DNA Vector | 1297 | ||
| Viral RNA Vector | 1297 | ||
| Viral Delivery | 1297 | ||
| Bacterial Delivery | 1297 | ||
| Nonmicrobial RNA Delivery | 1297 | ||
| Additional Considerations and Strategies for Active Vaccines | 1298 | ||
| Formulation | 1298 | ||
| Adjuvants | 1298 | ||
| Aluminum Salts. | 1298 | ||
| Other Licensed Adjuvants: MF59, AS03, AS04, Liposomes, and AS01. | 1298 | ||
| Adjuvants in Development. | 1299 | ||
| Bioinformatic Technologies and Vaccine Safety | 1299 | ||
| Delivery Systems | 1299 | ||
| Comparing Specific Vector Technologies. | 1300 | ||
| Adapting Strategies | 1300 | ||
| Mixed Vaccines | 1300 | ||
| Prime-Boost Regimens | 1300 | ||
| Combination Vaccines | 1301 | ||
| Antibody Preparations | 1301 | ||
| Polyclonal Antibodies | 1302 | ||
| Human Immunoglobulin and Antibody Fragment | 1302 | ||
| Monoclonal Antibodies | 1302 | ||
| Nonhuman | 1303 | ||
| Natural Human | 1303 | ||
| Recombinant Human | 1303 | ||
| Human Derived. | 1303 | ||
| Mouse Derived. | 1303 | ||
| Recombinant Humanized | 1303 | ||
| Recombinant Chimeric | 1303 | ||
| Conclusion | 1304 | ||
| References | 1304.e1 | ||
| 67 Development of Gene-Based Vectors for Immunization | 1305 | ||
| Nonviral Vectors and DNA Vaccines | 1305 | ||
| Mechanism of Action | 1307 | ||
| Animal Studies | 1307 | ||
| Prime-Boost Emergence | 1307 | ||
| Improved Immune Potency of the DNA Platform | 1308 | ||
| Molecular Adjuvants | 1310 | ||
| Increased Vaccine Dose | 1311 | ||
| Novel Transfection Reagents | 1311 | ||
| Vaccine Delivery Methods | 1311 | ||
| Clinical Studies | 1311 | ||
| Animal Studies | 1312 | ||
| RNA Vaccines | 1312 | ||
| Viral Vectors | 1313 | ||
| Replication-Defective Adenoviral Vectors | 1313 | ||
| Effect of Preexisting Antivector Immunity and Alternative Adenovirus Serotypes | 1314 | ||
| Poxvirus Vectors for Immunization | 1315 | ||
| Adeno-Associated Viruses | 1316 | ||
| Vectors in Development | 1316 | ||
| Cell Substrates | 1317 | ||
| Bacterial Vaccine Vectors | 1318 | ||
| Clinical Applications of Gene-Based Vector Technology | 1318 | ||
| References | 1319.e1 | ||
| 68 Technologies to Improve Immunization | 1320 | ||
| New Technologies Needed to Reduce Immunization Logistics Hurdles | 1320 | ||
| Point-to-Point Antigen Package Delivery | 1320 | ||
| Points of Origin: Vaccine Manufacturing Plants | 1320 | ||
| Purity and Stability | 1320 | ||
| Presentation | 1320 | ||
| Distribution and Storage Points | 1321 | ||
| Points of Care: Vaccine Administration Settings | 1321 | ||
| Current Vaccination Methods: Description and Logistical Hurdles | 1322 | ||
| Vaccination by Injection. | 1322 | ||
| Mucosal Vaccination. | 1322 | ||
| Destination Points: Inside the Vaccinee’s Antigen-Presenting Cells | 1322 | ||
| Logistical Hurdles in Special Settings | 1322 | ||
| Emergency Settings | 1322 | ||
| Low- and Middle-Income Countries | 1323 | ||
| Bioterror and Pandemic Settings | 1323 | ||
| Summary: Desirable Features of Practically Ideal Vaccine Delivery Systems | 1323 | ||
| New Technologies for Vaccine Stabilization, Packaging, Storage, Shipping, and on-Site Preparation: Points of Origin and Distribution Points | 1324 | ||
| Formulation | 1324 | ||
| Preservatives | 1324 | ||
| Thermostability | 1324 | ||
| Protection From High Ambient Temperatures. | 1324 | ||
| Freeze Protection. | 1324 | ||
| Dry-Format Delivery. | 1324 | ||
| Packaging | 1325 | ||
| Primary Packaging | 1325 | ||
| Vial and Ampoule (Vaccine and Diluent). | 1325 | ||
| Unit Dose Versus Multidose Formats. | 1325 | ||
| Preservative-Free Multidose Primary Packaging. | 1326 | ||
| Prefilled Syringes. | 1326 | ||
| Glass Prefilled Syringes. | 1326 | ||
| Plastic Prefilled Syringes. | 1326 | ||
| Compact Prefilled Autodisable Devices. | 1326 | ||
| Novel Primary Container Technologies. | 1326 | ||
| Safety Syringes. | 1328 | ||
| Secondary and Tertiary Packaging | 1328 | ||
| Environmentally Friendly Secondary Cartons and Tertiary Shipping Containers. | 1328 | ||
| On-Site Reconstitution and Filling | 1328 | ||
| Fully Integrated Reconstitution Technologies | 1330 | ||
| Syringe- or Cartridge-Based Technologies. | 1330 | ||
| Frangible Seal–Based Technologies (Tubes, Pouches, Blister Packs). | 1330 | ||
| Partially Integrated Reconstitution Technologies | 1330 | ||
| Diluent Transfer Technologies | 1331 | ||
| Hybrid Reconstitution Technologies | 1331 | ||
| Reconstitution Aids | 1331 | ||
| Summary | 1331 | ||
| New Technologies for Vaccine Administration: Vaccine Macrodelivery Systems at the Points of Care | 1331 | ||
| Subcutaneous and Intramuscular Injection | 1331 | ||
| Anatomy | 1332 | ||
| Immunological Rationale | 1332 | ||
| Jet Injection | 1332 | ||
| Multiuse Nozzle Jet Injectors. | 1332 | ||
| Disposable-Syringe Jet Injectors. | 1335 | ||
| Solid Dissolving Needles | 1335 | ||
| Cutaneous Vaccination | 1336 | ||
| Anatomy | 1336 | ||
| Immunological Rationale | 1336 | ||
| Traditional Methods | 1336 | ||
| Bifurcated Needle. | 1337 | ||
| Mantoux Method. | 1338 | ||
| Needle-Based Technologies | 1338 | ||
| Intradermal Adapters. | 1338 | ||
| Mini-Needles. | 1338 | ||
| Hollow Microneedles. | 1338 | ||
| Electroporation. | 1339 | ||
| Needle-Free Technologies | 1339 | ||
| Jet Injection. | 1339 | ||
| Microarray Patches. | 1341 | ||
| Solid-Coated Microarray Patches. | 1341 | ||
| Dissolving Microarray Patches. | 1342 | ||
| Powder Injection. | 1342 | ||
| Abrasion/Transcutaneous Delivery. | 1342 | ||
| Microporation. | 1343 | ||
| Mucosal Vaccination | 1343 | ||
| Anatomy | 1344 | ||
| Immunological Rationale | 1344 | ||
| Challenges for Mucosal Delivery of Vaccines | 1345 | ||
| Oral Vaccination | 1345 | ||
| Oral Ingestion (Intestinal Delivery). | 1345 | ||
| Oral Mucosal Vaccination (Sublingual or Buccal Delivery). | 1346 | ||
| Respiratory Vaccination | 1347 | ||
| Background. | 1347 | ||
| Upper Airway Vaccine Deposition | 1347 | ||
| Nasal Sprays. | 1347 | ||
| Nasal Drops. | 1349 | ||
| Nasal Nebulizer. | 1349 | ||
| Intranasal Dry Powders. | 1349 | ||
| Lower Airway Vaccine Deposition. | 1349 | ||
| Pulmonary Liquid Aerosols. | 1350 | ||
| Pulmonary Dry Powders. | 1350 | ||
| Vaccine Microdelivery Systems: Antigen Delivery to Destination-Point Antigen-Presenting Cells | 1352 | ||
| Replicating Systems | 1352 | ||
| Live Viruses and Bacteria | 1352 | ||
| DNA Vaccines | 1352 | ||
| Nonreplicating Vaccine Delivery Systems | 1352 | ||
| Adjuvants | 1352 | ||
| Conclusion | 1353 | ||
| Disclosure | 1353 | ||
| Acknowledgments | 1353 | ||
| References | 1353.e1 | ||
| 4 Vaccination of Special Groups | 1355 | ||
| 69 Vaccination of Immunocompromised Hosts | 1355 | ||
| Patients With Cancer | 1355 | ||
| Inactivated Vaccines (Nonlive Vaccines) | 1355 | ||
| Pneumococcal Vaccines | 1355 | ||
| Haemophilus influenzae Type B Vaccine | 1355 | ||
| Influenza Vaccine | 1356 | ||
| Tetanus Toxoid, Diphtheria Toxoid, and Inactivated Poliovirus Vaccine | 1357 | ||
| Hepatitis B Virus | 1357 | ||
| Other Nonlive (Nonreplicating) Vaccines | 1357 | ||
| Live Vaccines | 1357 | ||
| Varicella Vaccine | 1357 | ||
| Zoster Vaccine | 1358 | ||
| Measles, Mumps, and Rubella | 1358 | ||
| Other Live Vaccines | 1359 | ||
| Allogeneic Hematopoietic Stem Cell Transplantation Patients | 1359 | ||
| Nonlive Vaccines | 1359 | ||
| Pneumococcal Vaccines | 1359 | ||
| Haemophilus influenzae Type B Vaccine | 1360 | ||
| Influenza Vaccine | 1360 | ||
| Hepatitis B Virus Vaccine | 1361 | ||
| Tetanus Toxoid, Diphtheria Toxoid, and Inactivated Poliovirus Vaccines | 1361 | ||
| Human Papillomavirus Vaccine | 1361 | ||
| Cytomegalovirus Vaccine | 1361 | ||
| Other Nonlive Vaccines | 1361 | ||
| Live Vaccines | 1361 | ||
| Varicella Vaccine | 1361 | ||
| Measles, Mumps, and Rubella Vaccine | 1362 | ||
| Other Live Vaccines | 1362 | ||
| Autologous Hematopoietic Stem Cell Transplantation Recipients | 1362 | ||
| Nonlive Vaccines | 1362 | ||
| Influenza Vaccine. | 1362 | ||
| Pneumococcal Vaccine and Conjugated Haemophilus influenzae Type B Vaccine. | 1362 | ||
| Tetanus Toxoid, Diphtheria Toxoid, Pertussis, and Poliovirus Vaccine. | 1362 | ||
| Live Attenuated Vaccines | 1363 | ||
| Measles, Mumps, and Rubella Vaccine. | 1363 | ||
| Varicella-Zoster Virus Vaccine. | 1363 | ||
| Solid-Organ Transplant Recipients | 1363 | ||
| Nonlive Vaccines | 1363 | ||
| Pneumococci and Haemophilus influenzae Type B | 1363 | ||
| Influenza | 1363 | ||
| Tetanus, Diphtheria, and Pertussis Vaccines | 1364 | ||
| Hepatitis B Virus Vaccine | 1364 | ||
| Hepatitis A Virus | 1365 | ||
| Papillomavirus Vaccine | 1365 | ||
| Cytomegalovirus | 1365 | ||
| Other Nonlive Vaccines | 1365 | ||
| Live Attenuated Vaccines | 1365 | ||
| Varicella Vaccine | 1365 | ||
| Measles, Mumps, and Rubella | 1366 | ||
| Other Live Vaccines | 1366 | ||
| Primary Immunodeficiency Diseases | 1366 | ||
| Defects of the Innate Immune System | 1366 | ||
| Nonlive Vaccines | 1366 | ||
| Pneumococcal, Haemophilus influenzae Type B, Meningococcal Vaccine. | 1366 | ||
| Tetanus Toxoid, Diphtheria Toxoid, Inactivated Poliovirus, and Acellular Pertussis Vaccine. | 1367 | ||
| 5 Public Health and Regulatory Issues | 1421 | ||
| 73 Immunization in the United States | 1421 | ||
| Immunization Recommendations | 1421 | ||
| U.S. Immunization Program | 1422 | ||
| History | 1422 | ||
| Roles of the U.S. Immunization Program | 1425 | ||
| Assuring Vaccine Purchase, Supply, and Distribution | 1425 | ||
| Assuring Access to Vaccines | 1427 | ||
| Control and Prevent Infectious Diseases | 1428 | ||
| Vaccine Effectiveness | 1429 | ||
| Conduct Surveillance for Immunization Coverage | 1430 | ||
| Sustain and Improve Immunization Coverage Levels | 1431 | ||
| Barriers to Vaccination | 1431 | ||
| Key Program Activities | 1432 | ||
| Reporting and Monitoring Adverse Events Following Vaccination. | 1432 | ||
| Operating Immunization Information Systems. | 1432 | ||
| Enforcing Laws and Regulations for Immunization. | 1433 | ||
| Using the Standards of Immunization Practices. | 1434 | ||
| Educating and Updating the Immunization Workforce. | 1435 | ||
| Communicating With the Public. | 1435 | ||
| Evidence-Based Strategies to Improve Coverage | 1435 | ||
| Supporting Provider-Based Interventions. | 1435 | ||
| Impact of Immunization Programs | 1436 | ||
| Occurrence of Disease | 1436 | ||
| Immunization Coverage | 1436 | ||
| Preschool Immunization | 1436 | ||
| Teens | 1437 | ||
| Adult Immunization | 1437 | ||
| Impact of the U.S. Program | 1438 | ||
| Conclusion | 1439 | ||
| Sources of Additional Information | 1439 | ||
| References | 1440.e1 | ||
| 74 Immunization in Europe | 1441 | ||
| Overview | 1441 | ||
| Policymaking Processes in European Countries | 1441 | ||
| Organizations Working in Immunization in the European Region | 1444 | ||
| WHO Regional Office for Europe | 1444 | ||
| UNICEF Regional Office for Central and Eastern European and the Commonwealth of Independent States | 1447 | ||
| European Union Institutions | 1447 | ||
| Procurement | 1449 | ||
| Surveillance of Vaccine-Preventable Diseases in the European Region | 1450 | ||
| Vaccines Used and Immunization Coverage in the European Region | 1451 | ||
| Diphtheria, Tetanus, and Pertussis Vaccines | 1451 | ||
| Haemophilus influenzae Type B Vaccine | 1451 | ||
| Hepatitis B Vaccine | 1454 | ||
| Human Papillomavirus Vaccine | 1454 | ||
| Influenza Vaccine | 1455 | ||
| Measles, Mumps, and Rubella Vaccines | 1455 | ||
| Meningococcal Vaccines | 1455 | ||
| Pneumococcal Conjugate Vaccines | 1455 | ||
| Polio Vaccine | 1456 | ||
| Rotavirus Vaccine | 1456 | ||
| Varicella Vaccine | 1456 | ||
| Challenges to Immunization in the European Region | 1456 | ||
| Vulnerable Groups | 1456 | ||
| Vaccine Hesitancy | 1457 | ||
| Vaccine Resistance Because of Religious Beliefs | 1457 | ||
| Anthroposophic Communities in German-Speaking Countries and Elsewhere | 1457 | ||
| Religious Groups in the Netherlands Rejecting Vaccination | 1458 | ||
| Availability of Vaccines | 1458 | ||
| Low Vaccine Uptake Leads to Outbreaks | 1458 | ||
| Silent Wild Poliovirus Circulation in Israel | 1459 | ||
| Vaccine Safety Issues | 1459 | ||
| Autism and Measles-Mumps-Rubella Vaccine | 1459 | ||
| Narcolepsy Associated With Use of an AS03-Adjuvanted Influenza A (H1N1)PDM09 Vaccine Produced and Used in Europe | 1461 | ||
| Adolescent and Adult Immunization Programs | 1462 | ||
| Vaccinology Training | 1462 | ||
| European Region Strategy for Strengthening National Immunization Systems | 1462 | ||
| European Vaccine Action Plan | 1462 | ||
| Measles and Rubella Elimination Goal | 1463 | ||
| Polio Eradication Goal | 1464 | ||
| Diphtheria Elimination Goal | 1464 | ||
| Immunization Registries | 1464 | ||
| Tailoring Immunization Programs | 1465 | ||
| European Immunization Week | 1465 | ||
| Conclusions | 1465 | ||
| References | 1465.e1 | ||
| 75 Immunization in the Asia-Pacific Region | 1466 | ||
| Vaccines Developed in and for the Asia-Pacific Region | 1467 | ||
| Japanese Encephalitis Vaccines | 1467 | ||
| Tickborne Encephalitis Vaccine | 1467 | ||
| Kyasanur Forest Disease Vaccine | 1467 | ||
| Hantavirus Vaccines | 1472 | ||
| Other Novel Vaccines Developed in the Asia-Pacific Region | 1473 | ||
| Clinical Development and Regulatory Approval | 1473 | ||
| Vaccine Production | 1478 | ||
| Vaccine Policy and Schedules | 1479 | ||
| Vaccine Delivery and Coverage | 1482 | ||
| Future Trends and Challenges | 1482 | ||
| Acknowledgments | 1485 | ||
| References | 1485.e1 | ||
| 76 Immunization in Developing Countries | 1486 | ||
| Global Vision for Vaccines and Immunization | 1488 | ||
| Progress With Achieving Global Goals | 1488 | ||
| Polio Eradication | 1488 | ||
| Measles and Rubella Elimination | 1489 | ||
| Maternal and Neonatal Tetanus Elimination | 1490 | ||
| Immunization Coverage and Equity | 1490 | ||
| Introduction of New Vaccines in Low- and Middle-Income Countries | 1492 | ||
| Innovation and Research | 1492 | ||
| Overcoming the Challenges | 1493 | ||
| Country Ownership, Management, and Financing of Immunization Programs | 1493 | ||
| Strengthening Health and Immunization Systems | 1495 | ||
| Human Resources | 1495 | ||
| Sustainable Supply of Vaccines at Affordable Prices | 1496 | ||
| Immunization Supply Chains | 1497 | ||
| Situation After Years of Neglect. | 1497 | ||
| Game-Changing Solutions to Renew Systems. | 1498 | ||
| Leveraging the True Thermostability of Vaccines. | 1498 | ||
| Extending the Reach of Vaccines With New Cold Chain Technologies. | 1499 | ||
| Improving the Quality of the Cold Chain With Continuous Temperature Monitoring Technologies. | 1499 | ||
| Moving Away From a Paper-Based Data Management System. | 1499 | ||
| Optimizing the Supply Chain Network Design. | 1499 | ||
| Synergies With Other Health Commodity Supply Chains. | 1500 | ||
| Private Sector Engagement in Immunization Supply Chains. | 1500 | ||
| Strengthening Human Resources for Effective Vaccine Management. | 1500 | ||
| Future Prospects and Opportunities. | 1500 | ||
| Information Systems: Monitoring and Evaluation of Immunization Programs | 1501 | ||
| Monitoring Program Inputs and Activities. | 1501 | ||
| Monitoring Vaccination Coverage. | 1501 | ||
| Register-Based Coverage Estimates. | 1501 | ||
| Administrative Reports. | 1501 | ||
| Community Surveys. | 1502 | ||
| Lot Quality Sample Surveys. | 1502 | ||
| Sero-Surveys. | 1503 | ||
| Triangulating Coverage Data From Different Sources: WHO-UNICEF Estimates of National Immunization Coverage. | 1503 | ||
| Acting on Coverage Data. | 1503 | ||
| Disease Surveillance. | 1504 | ||
| Passive Countrywide Reporting of Vaccine-Preventable Diseases and Outbreak Investigation. | 1504 | ||
| Active Countrywide Surveillance, With Laboratory Confirmation. | 1504 | ||
| Sentinel Site Surveillance. | 1505 | ||
| Special Studies. | 1505 | ||
| Use of Mathematical Models to Estimate Burden of Vaccine-Preventable Diseases and Impact of Vaccination. | 1505 | ||
| Monitoring Adverse Events Following Immunization. | 1505 | ||
| Enhancing Service Delivery | 1506 | ||
| Overview of Vaccines, Schedules, and Delivery Strategies. | 1506 | ||
| Strategies and Practices to Strengthen Routine Immunization Systems and Improve Immunization Coverage. | 1510 | ||
| Dropouts and Missed Opportunities. | 1511 | ||
| Use of Financial Incentives for Increasing Immunization Coverage. | 1511 | ||
| Fostering Integrated and Coordinated Approaches | 1511 | ||
| Conclusion | 1511 | ||
| References | 1511.e1 | ||
| 77 Community Protection | 1512 | ||
| Historical Background | 1512 | ||
| Theoretical Arguments | 1513 | ||
| Mass Action Approach | 1513 | ||
| Case Reproduction Numbers | 1515 | ||
| Estimation of R0 | 1516 | ||
| R0, Rapidity of Spread, and Herd Immunity Thresholds | 1517 | ||
| Implications of Population Heterogeneity | 1517 | ||
| Heterogeneity in Immune Status | 1518 | ||
| Implications of Heterogeneity in Immune Status for Vaccine Effects | 1519 | ||
| The Real World | 1519 | ||
| Smallpox | 1519 | ||
| Measles | 1520 | ||
| Rubella | 1521 | ||
| Mumps | 1522 | ||
| Chickenpox (Herpes Varicella-Zoster Virus) | 1522 | ||
| Pertussis | 1522 | ||
| Diphtheria | 1523 | ||
| Haemophilus influenzae Type B | 1523 | ||
| Streptococcus pneumoniae (Pneumococcus) | 1524 | ||
| Meningococcal Disease (Neisseria meningitidis) | 1524 | ||
| Tetanus | 1525 | ||
| Poliomyelitis | 1525 | ||
| Rotavirus | 1526 | ||
| Influenza | 1526 | ||
| Human Papillomaviruses | 1527 | ||
| Tuberculosis (and Leprosy) | 1528 | ||
| “Nonspecific Effects” | 1528 | ||
| Discussion | 1529 | ||
| Acknowledgment | 1531 | ||
| References | 1531.e1 | ||
| 78 Economic Analyses of Vaccine Policies | 1532 | ||
| Important Considerations in Quantitative Policy Analysis | 1533 | ||
| Perspective | 1533 | ||
| Time Frame | 1533 | ||
| Disease Burden | 1534 | ||
| Measures Used for Health States | 1534 | ||
| Economic Valuation of Health Outcome States | 1534 | ||
| Vaccine Program Characteristics | 1534 | ||
| Sensitivity Analysis | 1534 | ||
| Examples of Uses of Quantitative Policy Analysis | 1534 | ||
| Use of Models | 1534 | ||
| Routine Childhood Immunization | 1537 | ||
| Bacillus Calmette-Guérin | 1537 | ||
| Diphtheria, Tetanus, and Pertussis and Components | 1538 | ||
| Haemophilus influenzae Type B | 1538 | ||
| Hepatitis A | 1538 | ||
| Hepatitis B | 1539 | ||
| Human Papillomavirus | 1539 | ||
| Influenza | 1540 | ||
| Measles, Mumps, and Rubella | 1541 | ||
| Meningococcal Vaccines | 1541 | ||
| Pneumococcal Vaccines | 1542 | ||
| Poliomyelitis | 1542 | ||
| Rotavirus | 1543 | ||
| Varicella | 1543 | ||
| Malaria | 1543 | ||
| Dengue | 1544 | ||
| Specialized Vaccines | 1544 | ||
| Adenovirus | 1544 | ||
| Anthrax | 1544 | ||
| Cholera | 1544 | ||
| Japanese Encephalitis | 1544 | ||
| Typhoid | 1545 | ||
| Yellow Fever | 1545 | ||
| Vaccines in Development | 1545 | ||
| HIV/AIDS | 1545 | ||
| Group B Streptococcus | 1545 | ||
| Respiratory Syncytial Virus | 1545 | ||
| Other Economic Considerations | 1545 | ||
| Conclusion | 1545 | ||
| References | 1546.e1 | ||
| 79 Regulation and Testing of Vaccines | 1547 | ||
| Historical Perspective | 1547 | ||
| Federal Laws and Regulations | 1547 | ||
| Food and Drug Administration Modernization Act | 1547 | ||
| Pediatric Research Equity Act | 1548 | ||
| Food and Drug Administration Amendments Act | 1548 | ||
| Food and Drug Administration Safety and Innovation Act | 1550 | ||
| Prescription Drug User Fee Act | 1551 | ||
| Federal Regulations and Food and Drug Administration Guidance | 1551 | ||
| Collaborations Between the Food and Drug Administration and National and International Partners | 1552 | ||
| Managed Review Process | 1552 | ||
| Meetings With Sponsors | 1554 | ||
| Stages of the Regulatory Review of Vaccine Products | 1554 | ||
| Premarketing Phase | 1554 | ||
| Investigational Phase | 1554 | ||
| Licensing Phase | 1556 | ||
| Postmarketing Phase | 1557 | ||
| Adverse Event Monitoring (Postlicensure Follow-Up) | 1557 | ||
| Innovative Systems for Evaluating Vaccine Safety Postmarketing | 1558 | ||
| Postlicensure Manufacturing Changes | 1558 | ||
| Accelerating Availability of Vaccines and Pathways to Licensure | 1558 | ||
| Vaccine Testing | 1560 | ||
| Product Labeling and Advertising | 1561 | ||
| Special Considerations | 1562 | ||
| Adjuvants | 1562 | ||
| Vaccines Against Global Infectious Diseases, Emerging Infectious Diseases, and Biothreat Agents | 1563 | ||
| Conclusion | 1564 | ||
| Acknowledgments | 1565 | ||
| References | 1565.e1 | ||
| 80 Regulation of Vaccines in Europe | 1566 | ||
| Marketing Authorization | 1566 | ||
| Marketing Authorization Procedures in the European Union | 1566 | ||
| National Procedure | 1566 | ||
| Decentralized Procedures | 1566 | ||
| Centralized Procedure | 1566 | ||
| Preauthorization Evaluation of Benefit and Risk | 1567 | ||
| Data Requirements for New Vaccines | 1567 | ||
| Efficacy | 1567 | ||
| Safety | 1567 | ||
| Authorization Based on Limited Data | 1568 | ||
| Scientific Advice and Authorization of Clinical Trials | 1568 | ||
| Requirements for Pediatric Medicinal Products | 1568 | ||
| Medicinal Products Intended for Markets Outside the European Union | 1569 | ||
| Risk Management | 1569 | ||
| Postauthorization Evaluation of Benefits and Risks | 1569 | ||
| Communication of Benefits and Risks | 1571 | ||
| Conclusion | 1572 | ||
| Acknowledgment | 1572 | ||
| References | 1572.e1 | ||
| 81 Regulation of Vaccines in Low- and Middle-Income Countries | 1573 | ||
| Regulation of Vaccines in Low- and Middle-Income Countries | 1573 | ||
| Vaccines of Assured Quality and Functionality of National Regulatory Authorities: Global Status and Trends | 1573 | ||
| World Health Organization Prequalification Program for Vaccines | 1574 | ||
| Initiatives to Strengthen Medicines Regulatory Systems in Developing Countries for Regulatory Oversight of Vaccines | 1576 | ||
| Five Steps for Capacity Building: Assessment and Institutional Development Program | 1576 | ||
| World Health Organization Observed Audits: Enforcement of Good Manufacturing Practices | 1578 | ||
| Parallel Regulatory Review: Example of Vaccines Against Meningococcal Conjugate A and Japanese Encephalitis Vaccines | 1579 | ||
| Strengthening Oversight and Monitoring of Clinical Trials for New Vaccines | 1579 | ||
| Technical Support and Learning Opportunities for Regulators From Developing Countries | 1580 | ||
| Leverage of Regulatory Decisions Made Elsewhere: Expedited Review of Imported Prequalified Vaccines for Use in National Immunization Programs | 1580 | ||
| Future Directions | 1581 | ||
| Preventing Duplication of Effort | 1581 | ||
| Strengthening Vaccine Safety Systems | 1581 | ||
| Increasing and Sustaining Global Supply of Vaccines: Investing in Developing Countries as a Source of Affordable Vaccines of Assured Quality | 1582 | ||
| Regulatory Pathways for Vaccines Manufactured in Developed Countries but Intended for Use in Developing Countries—Article 58 | 1582 | ||
| Acknowledgment | 1583 | ||
| References | 1583.e1 | ||
| 82 Vaccine Safety | 1584 | ||
| Methods of Monitoring Immunization Safety | 1584 | ||
| Prelicensure Evaluations of Vaccine Safety | 1584 | ||
| Postlicensure Evaluations of Vaccine Safety | 1585 | ||
| Passive Reporting Systems, Including the Vaccine Adverse Event Reporting System | 1586 | ||
| Postlicensure Clinical Trials and Phase IV Surveillance Studies | 1587 | ||
| Large Linked Databases, Including the Vaccine Safety Datalink. | 1587 | ||
| Clinical Centers, Including the Clinical Immunization Safety Assessment Centers. | 1588 | ||
| Safety of Mass Immunization Campaigns | 1588 | ||
| Weighing the Evidence and Assessing Causality | 1589 | ||
| Vaccine Safety Controversies and Misconceptions | 1590 | ||
| Whole-Cell Pertussis Vaccine Causes Permanent Brain Damage | 1590 | ||
| Deaths Following Vaccination: Temporal Association Versus Causality | 1590 | ||
| Vaccines Cause Cancer | 1590 | ||
| Safety of the Immunization Schedule and Simultaneous Vaccinations | 1590 | ||
| Vaccines Weaken the Immune System | 1591 | ||
| Vaccines Cause Autoimmunity | 1592 | ||
| Evidence That Vaccines Do Not Cause Autoimmunity | 1592 | ||
| Vaccines Cause Allergies and Asthma | 1592 | ||
| Evidence That Vaccines Do Not Cause Asthma | 1593 | ||
| Vaccines Cause Autism and Other Developmental Disabilities | 1593 | ||
| Aluminum in Vaccines Is Harmful | 1594 | ||
| Formaldehyde in Vaccines Is Harmful | 1594 | ||
| Vaccines Contain DNA From Aborted Human Fetuses | 1594 | ||
| Safety of Human Papillomavirus Vaccine | 1594 | ||
| Narcolepsy Associated With AS03-Adjuvanted Pandemic H1N1 Influenza Vaccine | 1595 | ||
| Vaccine Risk Communication | 1595 | ||
| Risk Perception | 1596 | ||
| Factors That Can Influence Parental Vaccine Acceptance | 1596 | ||
| Depth of Information | 1596 | ||
| Timing of Information | 1596 | ||
| Information Sources and Social Media | 1596 | ||
| Personal Experience | 1597 | ||
| Health Literacy | 1597 | ||
| Evaluating and Addressing Vaccine Safety Concerns: Role of Healthcare Practitioners and Public Health Professionals | 1597 | ||
| Importance of Educating Parents Concerned About Vaccines | 1598 | ||
| Future Considerations | 1598 | ||
| Acknowledgments | 1600 | ||
| References | 1600.e1 | ||
| 83 Legal Issues | 1601 | ||
| Vaccine Liability Before 1986 | 1601 | ||
| National Childhood Vaccine Injury Act | 1602 | ||
| National Vaccine Injury Compensation Program | 1602 | ||
| Purpose and Goals | 1602 | ||
| Structure and Process | 1608 | ||
| Implementation and Program Experience | 1610 | ||
| Vaccine Injury Compensation Program Cases Since 1986 | 1612 | ||
| Modifying the Vaccine Injury Table | 1617 | ||
| Medical Review of Claims | 1618 | ||
| Diphtheria, Tetanus, and Pertussis Vaccines | 1618 | ||
| DTP/DTP-Hib Vaccines | 1618 | ||
| Tetanus-Containing Vaccines | 1619 | ||
| Measles-Mumps-Rubella Vaccines | 1619 | ||
| Varicella Vaccine | 1619 | ||
| Hepatitis B Virus Vaccine | 1619 | ||
| Polio Vaccines | 1620 | ||
| Rotavirus Vaccine | 1620 | ||
| Hepatitis A Virus Vaccines | 1621 | ||
| Meningococcal Vaccines | 1621 | ||
| Influenza Vaccines | 1621 | ||
| Human Papillomavirus Vaccines | 1621 | ||
| Issues of Interest | 1622 | ||
| Related Liability Protection and Compensation Schemes | 1623 | ||
| Vaccine Liability Since 1986 | 1624 | ||
| Risk to Healthcare Professionals | 1625 | ||
| Other Situations in Which Suits Are Not Barred by the National Childhood Vaccine Injury Act | 1625 | ||
| International Compensation Programs | 1625 | ||
| The Power to Compel Vaccination | 1626 | ||
| Summary, Conclusions, and Future Implications | 1628 | ||
| Acknowledgments | 1630 | ||
| References | 1630.e1 | ||
| 84 Ethics | 1631 | ||
| Ethical Issues Unique to Vaccination | 1631 | ||
| Ethics of Prevention Versus Ethics of Treatment | 1631 | ||
| Target Populations and the Routinization of Vaccines | 1631 | ||
| Ethical Considerations in the Vaccine Life Cycle: an Overview | 1632 | ||
| Research and Development | 1632 | ||
| Licensure and Safety Monitoring | 1633 | ||
| Vaccine Supply, Access, and Financing | 1633 | ||
| Vaccination Requirements, Hesitancy, and Refusal | 1634 | ||
| Special Topics in Vaccine Ethics | 1635 | ||
| Healthcare Providers | 1635 | ||
| Vaccination in the Developing World | 1635 | ||
| Eradication Campaigns | 1635 | ||
| Vaccines and Public Health Emergencies | 1636 | ||
| The Future of Vaccine Ethics | 1636 | ||
| References | 1637.e1 | ||
| Appendix Websites and Applications for Mobile Devices With Information About Immunization | 1638 | ||
| Centers for Disease Control and Prevention (CDC) Websites | 1638 | ||
| National Center for Immunization and Respiratory Diseases (NCIRD) | 1638 | ||
| Morbidity and Mortality Weekly Report (Weekly Publication) | 1638 | ||
| Influenza | 1638 | ||
| Immunization Safety Office (ISO) | 1638 | ||
| National Center for HIV/AIDS, Hepatitis, STD, and Tuberculosis Prevention (NCHHSTP) | 1638 | ||
| Traveler’s Health | 1638 | ||
| Other U.S. Government Immunization-Related Websites | 1638 | ||
| Centers for Medicare & Medicaid Services (CMS) | 1638 | ||
| Dale and Betty Bumpers Vaccine Research Center (VRC) | 1638 | ||
| Department of Defense: Defense Health Agency Immunization Healthcare Branch | 1638 | ||
| Department of Health and Human Services (HHS) | 1639 | ||
| Food and Drug Administration (FDA), Center for Biologics Evaluation and Research (CBER) | 1639 | ||
| National Vaccine Injury Compensation Program | 1639 | ||
| National Vaccine Program Office (NVPO) | 1639 | ||
| Vaccine Adverse Event Reporting System (VAERS) | 1639 | ||
| State Agencies and Programs | 1639 | ||
| State Immunization Websites | 1639 | ||
| State Immunization Coordinators | 1639 | ||
| State Mandates on Immunization and Vaccine-Preventable Diseases | 1639 | ||
| International Immunization-Related Websites | 1639 | ||
| Bill & Melinda Gates Foundation | 1639 | ||
| Edward Jenner Society | 1639 | ||
| End Polio Now | 1639 | ||
| Gavi, the Vaccine Alliance | 1639 | ||
| Global Polio Eradication Initiative | 1639 | ||
| International Vaccine Access Center (IVAC) | 1639 | ||
| Measles & Rubella Initiative | 1640 | ||
| Pan American Health Organization (PAHO) | 1640 | ||
| PATH | 1640 | ||
| Safe Injection Global Network (SIGN) | 1640 | ||
| Shot@Life | 1640 | ||
| Viral Hepatitis Prevention Board (VHPB) | 1640 | ||
| World Health Organization (WHO) | 1640 | ||
| Global Advisory Committee on Vaccine Safety (GACVS) | 1640 | ||
| Strategic Advisory Group of Experts on Immunization (SAGE) | 1640 | ||
| Vaccine Safety Net (VSN) | 1640 | ||
| Immunization Surveillance, Assessment and Monitoring | 1640 | ||
| English Language Resources From Non-U.S. Organizations | 1640 | ||
| Immunize Canada | 1640 | ||
| Canadian Paediatric Society’s “Caring for Kids” | 1640 | ||
| Department of Health, United Kingdom of Great Britain and Northern Ireland | 1640 | ||
| Health Canada, Immunization & Respiratory Infections Division | 1640 | ||
| Immunise Australia Program | 1641 | ||
| Organizations With Immunization-Related Websites | 1641 | ||
| 317Coalition | 1641 | ||
| Alliance for Immunization in Michigan (AIM) | 1641 | ||
| American Academy of Family Physicians (AAFP) | 1641 | ||
| American Academy of Pediatrics (AAP) | 1641 | ||
| American College of Obstetricians and Gynecologists (ACOG) | 1641 | ||
| American College of Physicians (ACP) | 1641 | ||
| American Nurses Association (ANA) | 1641 | ||
| American Pharmacists Association (APhA) | 1641 | ||
| Association of Immunization Managers (AIM) | 1641 | ||
| Association for Prevention Teaching and Research (APTR) | 1641 | ||
| Center for Vaccine Awareness and Research, Texas Children’s Hospital | 1641 | ||
| Every Child by Two (ECBT) and Vaccinate Your Baby | 1641 | ||
| EZIZ Training, California Department of Public Health | 1641 | ||
| Group on Immunization Education (GIE) | 1641 | ||
| HealthMap Vaccine Finder | 1641 | ||
| History of Vaccines | 1642 | ||
| Immunization Action Coalition (IAC) | 1642 | ||
| National Academy of Medicine (NAM) | 1642 | ||
| Institute for Vaccine Safety (IVS) | 1642 | ||
| Institute for Safe Medication Practices National Vaccine Errors Reporting Program (VERP) | 1642 | ||
| Medscape | 1642 | ||
| Medical Assistants Resources and Training on Immunization (MARTi) | 1642 | ||
| National Adult and Influenza Immunization Summit (NAIIS) | 1642 | ||
| National Association of County and City Health Officials (NACCHO) | 1642 | ||
| National Association of School Nurses (NASN) | 1642 | ||
| National Conference of State Legislatures | 1642 | ||
| National Foundation for Infectious Diseases (NFID) | 1642 | ||
| PKIDs (Parents of Kids With Infectious Diseases) | 1642 | ||
| Sabin Vaccine Institute | 1643 | ||
| ShotbyShot | 1643 | ||
| Vaccine Education Center at The Children’s Hospital of Philadelphia (VEC) | 1643 | ||
| Vaccine Facts and Policy (VFAP) | 1643 | ||
| Vaccine Investigation and Online Information Network (VIOLIN) | 1643 | ||
| Voices for Vaccines (VFV) | 1643 | ||
| Organizations With Disease-Specific Websites | 1643 | ||
| Hepatitis | 1643 | ||
| Asian Liver Center (ALC) | 1643 | ||
| CDC’s Viral Hepatitis website | 1643 | ||
| Hepatitis B Foundation (HBF) | 1643 | ||
| National Task Force on Hepatitis B, Focus on Asian and Pacific Islander Americans | 1643 | ||
| National Viral Hepatitis Roundtable (NVHR) | 1643 | ||
| Human Papillomavirus (HPV) | 1643 | ||
| American Sexual Health Association’s National HPV & Cervical Cancer Prevention Resource Center | 1643 | ||
| CDC’s HPV website | 1643 | ||
| Influenza | 1644 | ||
| Childhood Influenza Immunization Coalition (CIIC) | 1644 | ||
| Families Fighting Flu (FFF) | 1644 | ||
| Meningitis | 1644 | ||
| Meningitis Angels | 1644 | ||
| National Meningitis Association (NMA) | 1644 | ||
| Rotavirus | 1644 | ||
| Rotavirus Vaccine Program | 1644 | ||
| Pharmaceutical Company Websites | 1644 | ||
| Index | 1645 | ||
| A | 1645 | ||
| B | 1648 | ||
| C | 1649 | ||
| D | 1652 | ||
| E | 1654 | ||
| F | 1656 | ||
| G | 1657 | ||
| H | 1658 | ||
| I | 1661 | ||
| J | 1666 | ||
| K | 1666 | ||
| L | 1666 | ||
| M | 1668 | ||
| N | 1671 | ||
| O | 1673 | ||
| P | 1673 | ||
| Q | 1678 | ||
| R | 1678 | ||
| S | 1680 | ||
| T | 1683 | ||
| U | 1686 | ||
| V | 1686 | ||
| W | 1689 | ||
| X | 1690 | ||
| Y | 1690 | ||
| Z | 1690 | ||
| Inside Back Cover | ibc1 |