Vaccines have prevented more illness and death than any other medical intervention, yet there are still exciting new challenges requiring imaginative soloutions in order to develop new vaccines and to have them reach the people most in need. This book reveals for the non-expert, with specific examples, the scientific opportunities and potential impact of vaccines, their unique economic and ethical challenges, and the special problems of producing vaccines, designing clinical vaccine trials, and introducing them into widespread use.
Table of Contents:
Dedication
Contributors
Preface
Introduction-Global Burden of Disease addressed by Current Vaccines and Vaccines in the Development Pipeline
Part I: Understanding Vaccine Impact at Population and Individual Levels
Chapter 1: The Impact of Vaccination on the Epidemiology of Infectious Diseases
Abstract
1. Introduction
2. Changing world
3. Basic epidemiological principles
4. Vaccine coverage required to interrupt transmission
5. A shifting average age at infection
6. Perverse effects of vaccination
7. Troughs in herd immunity as a consequence of the introduction of cohort based vaccination
8. Indirect and direct effects of vaccination-benefits of herd immunity
9. Health economics-costs and benefits of vaccination
10. Partially effective vaccines-efficacy versus duration of protection
11. Spatial and other heterogeneities
12. Natural selection and mass vaccination
13. Discussion
Chapter 2: How Vaccines Work
Abstract
1. Introduction
2. What follows a vaccine injection? Basis of antibody response to protein vaccines
3. Vaccine antigen recognition
4. Germinal center reaction
5. Building B-cell memory
6. Response to polysaccharide vaccines
7. Vaccine-induced T-cell responses
8. Innate immunity and T-cell differentiation
9. Vaccine-induced T-cell memory
10. Conclusions
Part II: How to Design, Assess and Produce Vaccines
Chapter 3: Vaccine Design in the 21st Century
Abstract
1. Introduction
2. Strategies for modern vaccine design
3. Conclusions and future outlook
Acknowledgments
Chapter 4: Vaccine Adjuvants
Abstract
1. Brief adjuvant history
2. Adjuvants in current approved vaccines
3. Adjuvant development
4. Mechanisms of action
5. Formulation
6. Adjuvants for unmet needs; HIV and tuberculosis vaccines
Chapter 5: Vaccine Production: Main Steps and Considerations
Abstract
1. Manufacturing basics
2. Considerations for manufacturing vaccines
3. Vaccine challenges from the industry perspective
4. Manufacturing dilemmas
Acknowledgments
Chapter 6: How are Vaccines Assessed in Clinical Trials?
Summary
1. The vaccine testing paradigm
2. Ethical issues
3. Good Clinical Practices
4. Phase 1
5. Phase 2
6. Phase 3
7. Issues to be considered in designing a Phase 3 vaccine efficacy trial
8. Phase 4 surveillance and studies to monitor product safety and the impact on disease burden with vaccine use post-licensure
9. Summary note
Chapter 7: Immunological Correlates of Vaccine-Mediated Protection
Abstract
1. Introduction
2. Definitions
3. Indentifying correlates of protection
4. Statistical methods for evaluating correlates of protection
5. Correlates of protection as effector or pathway correlates
6. Known correlates of protection for vaccines
7. Conclusions
Part III: Vaccine Safety
Chapter 8: How Vaccine Safety is Monitored
Abstract
1. Introduction
2. Vaccine development
3. Investigational new drug (IND) application
4. Clinical trials
5. Regulatory approval
6. Vaccine recommendations
7. Postmarketing surveillance and special studies
8. Standardized case definitions
9. Clinical assessment and individual-level causality assessment
10. Compensation for vaccine injuries
11. Coordination
12. Investigations of reports of MMR and autism: an example
13. Summary
Chapter 9: Vaccination and Autoimmune Diseases
Abstract
1. Introduction
2. Understanding infection-associated autoimmunity
3. The risk of vaccine-associated autoimmunity
4. Vaccine-attributable autoimmune diseases
5. Allegations of autoimmune adverse effects
6. New generation vaccines and autoimmunity: approaches toward early risk assessment
7. Vaccination in patients with chronic autoimmune diseases
8. Conclusions
Part IV: New Vaccination Strategies
Chapter 10: Maternal Immunization: Protecting Vulnerable Populations
Abstract
1. Introduction
2. Background
3. Vaccines currently administered to pregnant women
4. Potential maternal vaccines
5. Safety of maternal immunization
6. Potential obstacles for maternal immunization
7. Clinical trial designs
8. Social and ethical issues
9. Summary
Chapter 11: New Challenges for Pertussis Vaccines
Abstract
1. Historical perspective
2. Changing epidemiology
3. Current use of pertussis vaccines
4. Relative merits of acellular and whole-cell pertussis vaccines
5. Remaining gaps in control of pertussis
6. Prospects for new pertussis vaccines
7. Interim measures for the control of pertussis
8. Summary and conclusions
Part V: Recently Introduced Vaccines
Chapter 12: Pneumococcus, Pneumococcal Disease, and Prevention
Abstract
1. Introduction
2. The organism and associated pathology
3. Epidemiology of pneumococcal disease
4. Immunology
5. Vaccines against pneumococcus
6. Future vaccine approaches
7. Conclusions
Chapter 13: Human Papillomavirus Vaccines
Abstract
1. Introduction
2. Burden of HPV-associated disease
3. HPV vaccines: rationale
4. Licensed prophylactic HPV vaccines
5. Vaccine efficacy
6. Implementation and effectiveness
7. Vaccine impact
8. Vaccine-induced immune responses
9. Safety
10. Alternative dosage schedules
11. Concluding remarks
Chapter 14: Rotavirus Vaccines
Abstract
1. Biology of rotavirus
2. Rotavirus disease and treatment
3. Burden and epidemiology of rotavirus
4. Rationale for rotavirus vaccine development
5. The first licensed rotavirus vaccine-Rotashield
6. Current internationally licensed rotavirus vaccines-Rotarix™ and RotaTeq
7. Remaining issues and challenges for rotavirus vaccines
8. Conclusions
Disclaimer
Part VI: New Approaches for Needed Vaccines
Chapter 15: Antiviral Vaccines: Challenges and Advances
Abstract
1. Introduction
2. Types of currently licensed antiviral vaccines
3. How antiviral vaccines mediate protection?
4. Modern approaches to studying immune responses induced by antiviral vaccines
5. Next generation vaccine platforms
6. Harnessing the technological advances to develop vaccines against challenging and emerging viruses
7. Summary
Acknowledgments
Chapter 16: New Approaches for Needed Vaccines: Bacteria
Abstract
1. Background
2. Gaps and targets
3. Classical approaches for making bacterial vaccines
4. The impact of genomics on bacterial vaccine development
5. Reverse vaccinology
6. Live vaccines against bacteria
7. Vaccines based on membrane complexes
8. Killed oral vaccines
9. Bioconjugates
10. Concluding remarks
Acknowledgment
Chapter 17: Vaccines Against Parasites
Abstract
1. Vaccination against malaria
2. Vaccination against leishmaniasis
3. Vaccination against helminths
Part VII: Major Global Vaccine Challenges
Chapter 18: Tuberculosis Vaccines
Abstract
1. Introduction
2. Tuberculosis
3. The current TB vaccine - BCG
4. New strategies toward vaccination against TB
Acknowledgments
Chapter 19: Major Global Vaccine Challenges: Recent Progress in Malaria Vaccine Development
Abstract
1. Introduction
2. Preerythrocytic vaccine candidates
3. Blood-stage vaccine candidates
4. Sexual stage vaccine candidates
5. Multiple-stage vaccine candidates
6. Vaccine candidates against malaria in pregnancy
7. P. vivax vaccine development status
8. Conclusions
Acknowledgment
Chapter 20: AIDS Vaccines
Abstract
1. Introduction
2. Immune responses to HIV: what is needed?
3. Efficacy trials of candidate vaccines
4. Planned efficacy trials of candidate HIV vaccines
5. New HIV vaccine concepts on the horizon
6. Vaccines and the HIV cure agenda
7. Conclusions
Chapter 21: Influenza Vaccines and Vaccination Strategies
Abstract
1. Introduction
2. The influenza virus
3. Influenza disease and burden of illness
4. Influenza vaccines
5. Non-replicating influenza vaccines
6. Safety of non-replicating vaccines
7. Immunogenicity of inactivated vaccines
8. Efficacy and effectiveness
9. Populations of interest
10. Live-attenuated influenza vaccines (LAIVs)
11. Immunogenicity
12. Safety
13. Efficacy and effectiveness
14. Influenza vaccines in development
15. Vaccination policy and programs
16. Challenges of influenza vaccine programs in low resource settings
17. Summary
Part VIII: Ethical Considerations
Chapter 22: Ethical Considerations in Vaccine Trials in Resource-Limited Settings
Abstract
1. Introduction
2. Ethical considerations
3. Conclusions
Acknowledgment
Part IX: Vaccine Economics
Chapter 23: Economic Considerations for the Development of Global Vaccines: a Perspective From the Vaccine Industry
Abstract
1. Program valuation and portfolio management
2. Conclusions
Chapter 24: Introduction of Vaccines Into National Programs
Abstract
1. Introduction
2. Political considerations
3. Natural history and epidemiologic considerations
4. Regulatory considerations
5. Program Considerations
6. Economic considerations
7. Financing
8. Modeling the impact-efficiency or opportunity costs
9. Global efforts to support vaccines introduction
Chapter 25: Transitioning Immunization Into the Health Care System: Strengthening Routine Immunization in India
Abstract
1. Introduction
2. Background: India’s Universal Immunization Programme
3. Improving coverage
4. New vaccine introduction
5. Health system strengthening
6. Conclusions
Part X: Trust in Vaccines
Chapter 26: Vaccine Acceptance
Abstract
1. Introduction
2. From vaccine hesitancy to vaccine demand: Making sense of terminology and concepts
3. Determinants of vaccine hesitancy, drivers of vaccine acceptance
4. Vaccination decisions and risk perception
5. Communication about vaccination and risk perception
6. Conclusions
Chapter 27: Trust and Confidence in Vaccines: Tales of Three Vaccines, Lessons for Others
Abstract
1. Three case studies of vaccine hesitancy and distrust
2. Lessons learned
3. The need for evidence-based recommendations for the future
Acknowledgment
Part XI: Future Challenges
Chapter 28: Vaccines for Emerging Viral Diseases
Abstract
1. Introduction
2. Ebola
3. Chikungunya
4. Middle East Respiratory Syndrome Coronavirus
5. Conclusions
Acknowledgments
Chapter 29: Cancer Immunotherapy by Checkpoint Blockade
Abstract
1. Introduction
2. Cancer immunotherapy
3. Regulation of immune responses
4. Applications for cancer therapy
5. Application for infectious diseases
6. Summary and future perspectives
Chapter 30: Adoptive Cellular Therapy With Synthetic T Cells as an “Instant Vaccine” for Cancer and Immunity
Abstract
1. Introduction
2. Discovery of T cells with stem-cell-like qualities
3. Approaches to engineer lymphocytes using synthetic biology
4. Design of CAR T cells
5. Lessons from clinical trials on patients with chronic infection
6. Clinical trials with CAR T cells directed against B-cell malignancies
7. Toxicities and management
8. Conclusions and future challenges
Subject Index
