DNA vaccine

Author: Li Qihán, Li Qihán et al. Translated
Publisher:
Publishing Time: 2005-01-01
Features: This book is one of the series "Modern Biotechnology and Pharmaceutical Technology" published by Chemical Industry Press. As of now, 13 volumes of this series have been published. The book comprehensively and thoroughly elaborates on the emerging research field of DNA vaccines. It is divided into 19 chapters. First, it reviews and looks ahead to vaccinology; then, it elaborates on the basic theory of DNA immunity, fully analyzing the theoretical foundation and background of DNA vaccines as a discipline. Next, it focuses on DNA vaccines that have entered or are expected to enter clinical trials (including anti-RNA virus, anti-herpes virus, anti-bacterial pathogens, and DNA vaccines for cancer treatment, allergic diseases, and anti-HIV gene immunization). Finally, it discusses related technologies of DNA applications, such as immunization regimens, characteristics of construction techniques, adjuvants, and safety. The book starts from theory, explains techniques, and describes applications, making it a work that combines theoretical nature, advancement, and practicality. It is suitable for technical personnel engaged in basic medicine, immunology, vaccinology, and vaccine research and development, as well as for graduate students in related fields.
Table of Contents
Chapter 1 Historical Review and Future Prospects of Vaccinology: The Origin and Development of an Integrated and Dynamic Discipline
Translated by Li Qihán and Jiang Li
1.1 Abstract
1.2 The History of Infectious Diseases, Science, and Vaccines Before 1875
1.2.1 Ancient Times
1.2.2 The Dark Ages
1.2.3 The Middle Ages
1.2.4 The Renaissance and Christian Reformation
1.2.5 The Separation of Church and State and the Rise of Science
1.2.6 The 18th Century
1.2.7 The 19th Century to 1875: New Applications of Science
1.3 The Glorious Age of Empiricism: 1875–1930
1.4 The Early Years of the Modern Era of Vaccinology: Transition, War, and Recovery
1.4.1 The Transition Period
1.5 The Modern Era of Vaccinology: Overview and Achievements
1.5.1 The Establishment of a New Virus and Cell Biology Research Department at Merck Research Laboratories
1.5.2 Bacterial Vaccines
1.5.3 Live Virus Vaccines
1.5.4 Inactivated Virus Vaccines
1.6 The New Era of Vaccinology (A Review of 1990–2000): A Period of Stagnation in Vaccine Development and an Explosion of New Scientific Knowledge
1.7 The Future of Vaccinology Based on New Technologies
1.7.1 Public Funding for Basic Research
1.8 The Application of Vaccines in the Future
1.8.1 The Current State of Public Health Today
1.8.2 Opportunities, Development, and Political and Economic Needs for Using Vaccines to Control Diseases
1.8.3 Encouragement for Businesses
1.8.4 The Goals of the New York Declaration
1.9 The Covenant Between Science and Society
1.9.1 Support for Publicly Funded Disciplines
1.9.2 Supervision and Control of Publicly Funded Disciplines
1.9.3 Evaluation of Grant Applications
1.9.4 Promoting Science Education in the United States
1.10 Collaboration Between the Scientific Community and Industry to Develop New Products for the Public
1.11 A Call to Vaccine Research Companies
1.12 Recombinant DNA Vaccines
References
Chapter 2 Dendritic Cells: Important Adjuvants in DNA Immunity
Translated by Liu Longding and Shi Haijing
2.1 Abstract
2.2 Dendritic Cells: Effective Initiators of T Cell Immunity
2.2.1 Microbes and Cell Extracts as Weak Immunogens for T Cell-Mediated Immunity
2.2.2 Input/Output of T Cell-Dependent Immunity in Culture Systems and Antigen-Presenting Cells
2.2.3 The Co-Stimulatory Properties of Dendritic Cells
2.2.4 The Role of Dendritic Cells in Initiating MHC-Restricted Immunity
2.3 The Maturation of Dendritic Cells: Regulatory Points for Initiating Immune Reactions in Culture Systems
2.3.1 The Culture and Maturation of Epidermal Langerhans Cells
2.3.2 The Timeliness of Antigen Uptake and T Cell Stimulation by Dendritic Cells
2.3.3 Dendritic Cell Maturation Stimuli, Including the Selection of CpG Oligodeoxynucleotides
2.4 Dendritic Cells as Natural Adjuvants
2.4.1 The Distribution of Dendritic Cells in the Body
2.4.2 DCs Effectively Capture Antigens in the Body
2.4.3 Using Rodents to Study Antigen-Pulsing of DC-Initiated T Cell-Dependent Immunity
2.5 Dendritic Cells Control the Quality of Immune Reactions in the Body: New Discoveries in Human Immune Research
2.5.1 Preliminary Applications of DCs in Activating Patient Anti-Tumor Immunity
2.5.2 DCs Carrying Antigens Safely and Effectively Enhance T Cell Immunity in Healthy Volunteers
2.5.3 Mature DCs Enhance the Quality and Affinity of T Cell Reactions
2.5.4 Immature DCs Suppress and Regulate Immune Reactions Based on DC Tolerance Mechanisms
2.6 Other Types of Immune Reactions and Dendritic Cell Subsets
2.6.1 Dendritic Cells Not Only Affect T Cells but Also Other Types of Lymphocytes
2.6.2 DCs Connect Innate and Acquired Immunity
2.6.3 DC Subsets
2.7 Potential Mechanisms of Some Dendritic Cell Functions
2.7.1 The Formation of MHC-Peptide Complexes—Signal 1
2.7.2 T Cell Binding and Co-Stimulation—Signal 2
2.7.3 Mobilization and Migration in the Body—Signal 3
2.8 Dendritic Cells as Mediators of DNA Immunity
2.8.1 Bone Marrow-Derived Cells (Non-Somatic) Present Antigens Encoded by DNA Vaccines
2.8.2 DCs Are Directly Transduced in Mice Receiving DNA Immunization
2.8.3 After the Initiation Phase of DNA Immunization, Do Dendritic Cells Continue to Cross-Present Antigens from Other DNA Immune Cells, and Is This Important for Enhancing Vaccine Immunity?
2.8.4 The Adjuvant Function of DCs in DNA Vaccines and the Response to CpG Oligodeoxynucleotides (ODNs)
2.9 Conclusion
References
Chapter 3 Activation of the Innate Immune System by DNA Vaccines
Translated by Li Yiming and Jiang Li
3.1 Introduction
3.2 Toll-Like Receptors and Their Ligands
3.3 TLR9 Recognition of Bacterial DNA
3.4 Summary
References
Chapter 4 B Cell Reactions Induced by DNA Vaccines
Translated by Ma Shaohui and Liao Yun
4.1 Preface
4.2 The Initiation of Humoral Immunity
4.3 DNA Vaccines
4.4 Gene Gun Delivery
4.5 Antigen Presentation After Gene Gun Immunization
4.6 The Site of B Cell Response Induced by DNA Gun Injection
4.7 The Role of T Helper Cells in Early B Cell Responses
4.8 DNA Immunization Expressing Human Fc Fusion Protein Enhances B Cell Activity
4.9 Germinal Centers
4.10 The Reactivity of Newborn B Cells
4.11 Newborn DNA Immunization with Gene Gun
4.12 Conclusion
References
Chapter 5 Immune Responses to DNA Vaccines: Induction of CD8+ T Cells
Translated by Li Jianfeng and Chen Yang
5.1 The Importance of CD8+ T Cells in Controlling Most Viral Infections
5.2 Antigen Presentation Pathways Determine the Host's Immune Response
5.3 Design of Viral and Bacterial Vaccines
5.4 Effector Functions of CD8+ T Cells Generating Biological Activity
5.4.1 CD8+ T Cells Often Contain Perforin, a Pore-Forming Protein
5.4.2 CD8+ T Cells Can Induce Target Cell Apoptosis
5.4.3 CD8+ T Cells Release Antiviral Cytokines
5.5 Antigen Determinants for the Activation and Effector Functions of CD8+ T Cells
5.5.1 Brief Antigen Stimulation Can Effectively Drive Naive CD8+ T Cells to Become Memory Cells
5.5.2 Antigen-Specific CD8+ T Cells Are Highly Sensitive to Antigen Contact
5.5.3 CD8+ Memory Cells Are Effector Cells
5.6 How DNA Immunization Induces CD8+ T Cell Responses
5.6.1 Does DNA Immunization Rely on Protein Transfer from Transfected Cells to APCs?
5.6.2 Does DNA Immunization Rely on APC Absorption and Expression of Plasmids?
5.7 Examples and Characteristics of DNA Immunization Inducing CD8+ T Cells
5.7.1 DNA-Induced CD8+ T Cells Can Be Directly Measured In Vitro
5.7.2 DNA-Induced CD8+ T Cells Are Similar in Nature to Virus-Induced CD8+ T Cells
5.8 CD8+ T Cell Responses Induced by DNA in Humans
5.9 Enhancing DNA Vaccine-Induced CD8+ T Cell Responses
5.9.1 Immune Route
5.9.2 Linking Antigens to Heat Shock Proteins
5.9.3 Codon Optimization
5.9.4 Proteasome Targeting Peptides to Enhance Transport to the Endoplasmic Reticulum
5.9.5 Delivering the Coding Sequence Directly to the Endoplasmic Reticulum
5.9.6 Can the Protein Transduction Domain Improve the Effect of DNA Immunization?
5.9.7 Priming-Booster Immunization Strategy
5.10 Co-Given Immune Modulators
5.11 Summary
References
Chapter 6 Small Gene Vaccines for Inducing CD8+ T Cell Responses
Translated by Shen Yi and Zhao Hongling
6.1 Strategies for Building Better Vaccines
6.2 Review of Basic Knowledge
6.3 Number and Ratio
6.4 Leader Sequences
6.5 Small Genes with Multiple Determinants
6.6 Other Small Gene Vectors
6.7 Immune Contradictory Modification Methods: Rational Design of CD8+ T Cell Vaccines
References
Chapter 7 DNA Vaccines Against RNA Viruses
Translated by Pu Yan and Li Qihán
7.1 Introduction
7.2 DNA Vaccines Against Specific RNA Viruses
7.2.1 Influenza Virus
7.2.2 Hepatitis C Virus
7.3 Rabies Virus
7.4 Measles Virus
7.5 Respiratory Syncytial Virus
7.6 Rotavirus
7.7 Dengue Virus
7.8 Summary
References
Chapter 8 DNA Vaccines Against Herpes Viruses
Translated by Chen Wei and Wang Lichun
8.1 Abstract
8.2 Introduction
8.3 Using DNA Vaccines to Prevent and Treat Herpes Viruses
8.4 Boosting DNA Vaccines Against Herpes Viruses
8.5 Regulation of DNA Vaccine-Induced Immune Responses
8.6 Immune Regulation: Using DNA Vaccines to Inhibit Immune Pathology
8.7 Secondary Immunization (Prime-Boost) Strategy
8.8 Cross-Activation and DNA Immunization
8.9 Conclusion and Prospects
References
Chapter 9 Anti-HIV Gene Immunization
Translated by Fu Tao and Liu Longding
9.1 Global Spread of HIV
9.1.1 Expected Immune Responses
9.2 HIV-1 Envelope Glycoprotein Gene Vaccine
9.2.1 Characteristics of gp160
9.2.2 Immune Responses to gp160
9.2.3 Vaccine Research
9.3 Nucleocapsid Gene
9.4 Polymerase Gene
9.4.1 Human Immune Responses to RT
9.4.2 RT Drugs and CTL
9.4.3 RT Immunity
9.5 HIV-1 Early Genes and Additional Proteins
9.5.1 Natural Immune Responses
9.5.2 Additional Gene Immunization
9.6 Receptor Gene
9.7 Gene Complex or Multi-Gene Constructs
9.8 Small Animal Models for Measuring Challenge
9.9 Primate Models
9.9.1 DNA Vaccine Research
9.9.2 Experimental Immunotherapy
9.10 Immune Enhancement Related to Anti-HIV Protection
9.10.1 Codon Usage
9.10.2 Adjuvants for DNA Immunization
9.10.3 Vaccination Route
9.10.4 Advances in Viral Vectors or Attenuated Vaccines
9.11 DNA Immunization Against HIV in Humans
9.11.1 Immune Responses in HIV-Infected Immunosuppressed Patients
9.11.2 Therapeutic Immunization
9.11.3 Immunity and Antiretroviral Therapy
9.12 Planned Intermittent Treatment
9.13 Summary
References
Chapter 10 DNA Vaccines Against Bacterial Pathogens
Translated by Wu Wenjuan and Li Qihán
10.1 Abstract
10.2 DNA Vaccines Against Mycobacterial Infections
10.2.1 Pathogenic Mycobacteria
10.2.2 Challenges of Tuberculosis
10.2.3 Immune Protection Mechanisms Against Tuberculosis
10.2.4 TB Vaccines as Preventive Vaccines and Protective Antigen Recognition
10.2.5 DNA Vaccines as Post-Exposure Vaccines or Immunotherapeutic Agents
10.2.6 The Role of DNA Vaccines in Other Mycobacterial Diseases
10.2.7 Measures to Improve the Efficacy of Tuberculosis DNA Vaccines
10.2.8 Characteristics of Immune Responses After DNA Vaccination
10.3 DNA Vaccines for Other Bacterial Diseases
10.3.1 Anthrax
10.3.2 Borrelia burgdorferi
10.3.3 Brucella abortus
10.3.4 Chlamydia
10.3.5 Tetanus Clostridium
10.3.6 Pseudomonas pseudotuberculosis
10.3.7 Enterotoxigenic Escherichia coli
10.3.8 Francisella tularensis
10.3.9 Helicobacter pylori
10.3.10 Leptospira interrogans
10.3.11 Listeria monocytogenes
10.3.12 Mycoplasma pneumoniae
10.3.13 Pseudomonas aeruginosa
10.3.14 Salmonella typhi
10.3.15 Staphylococcus aureus
10.3.16 Streptococcus pneumoniae
10.3.17 Yersinia species
10.4 Summary
References
Chapter 11 DNA Vaccines for Cancer Treatment
Translated by Che Yanchun, Li Qihán, and Zhao Shudong
11.1 Abstract
11.2 Introduction
11.3 Classification of Tumor Antigens
11.4 Breast Cancer and Herceptin
11.5 Non-Hodgkin Lymphoma and Rituxan
11.6 Other Clinical Trials Using Antibodies for Passive and Active Immunotherapy
11.7 DNA Immunization
11.8 SV40 and Its Relevance to Human Infection and Cancer
11.9 SV40Tag and Its Role as a Target Antigen for Active Immunotherapy
11.10 Animal Models for SV40Tag Cancer Immunization
11.11 SV40Tag Cancer Immunology Research and the Role of Antibodies in Cancer Immunity
11.12 Examples of Tumor Immune Mechanisms Based on DNA Immunization Models
11.13 Stricter Tumor Models Show Antibodies Are Effective in Providing Protective Immunity
11.14 Other Research on Targeting Tumor Antigen-Specific DNA Immunization
11.15 Conclusion
References
Chapter 12 DNA Vaccines for Allergic Diseases
Translated by Dong Chenghong and Li Pingzhong
12.1 Abstract
12.2 Introduction
12.3 DNA Vaccines for Hypersensitivity: Overview
12.4 Primary Safety
12.5 Immunogenicity: Antigen Expression and Presentation
12.6 Antigen Dose and T Cell Differentiation
12.7 Mechanisms for Preventing Hypersensitivity
12.8 Prospects
References
Chapter 13 Immune Responses to Genetic Disease Gene Transfer
Translated by Xia Chunxiang and Liu Longding
13.1 Introduction
13.1.1 Immune Tolerance in Genetic Diseases
13.1.2 Antigen Processing and Presentation in Gene Therapy and Protein Replacement Therapy
13.2 Factors Affecting Immune Responses to Genetic Disease Gene Transfer
13.2.1 The Role of Vectors in Determining Transgene Product Immune Responses
13.2.2 The Effect of Vector Dose on Transgene Product Immune Responses
13.2.3 The Influence of Potential Mutations in the Host
13.2.4 The Route of Vector Administration
13.2.5 Tissue-Specific Promoters in Vectors
13.2.6 Tolerance Measures Before Vector Administration
13.2.7 Immunosuppression During Vector Administration
References
Chapter 14 Application of DNA Vaccines in Neonatal and Early Childhood Immunization
Translated by Guo Hongxiang and Shi Haijing
14.1 Abstract
14.2 New Antigen Delivery Systems Are Needed for Infant Immunization
14.2.1 Susceptibility of Newborns to Infection: What Characteristics Should Vaccines Have?
14.2.2 Immune Challenges Faced by DNA in Infants
14.3 Immune Responses After Neonatal DNA Immunization
14.3.1 Neonatal Tolerance or Immunity?
14.4 Factors Affecting the Type of Immune Response After DNA Vaccination in Newborn Animals
14.4.1 DNA Immunization Route and Methods
14.4.2 Induction of Th1/CTL Responses in Early Life Stages: The Effect of Immunostimulatory CpG Motifs in Plasmid Backbones on Responses
14.4.3 Formation and Type of Antigen Encoded: Significant Impact on Early Life
14.4.4 DNA Vaccine-Induced Adult-Like Antibody Responses: Is This an Improvement Over Traditional Vaccines?
14.4.5 Can DNA Immunization in Early Life Trigger Lifelong Responses?
14.5 Inhibitory Effects of DNA Vaccines and Maternal Antibodies
14.5.1 The Effect of the Relative Ratio of Maternal Antibodies and Vaccine Antigens
14.5.2 Maternal or Infant-Specific B Cell Epitopes
14.5.3 The Effect of Maternal Antibodies on T Cell Responses
14.5.4 Contradictory Results in Different Mouse Model Experiments
14.6 Optimizing DNA Immunization Strategies for Newborns
14.6.1 DNA Initial Immunization and Protein Boosting Immunization Strategy
14.6.2 Combined Immunization Using DNA and Other Delivery Systems
14.6.3 Other Methods
14.7 Conclusion and Prospects
References
Chapter 15 Using Attenuated Intracellular Bacteria for DNA Delivery
Translated by Chu Lihui and Che Yanchun
15.1 Intracellular Bacteria: From Pathogens to Vaccines—Overview
15.2 Comparison Between DNA Delivery and Naked DNA Immunization—Advantages and Disadvantages
15.3 Survival Strategies of Intracellular Bacteria
15.3.1 Listeria monocytogenes
15.3.2 Shigella flexneri
15.3.3 Salmonella enterica
15.4 Using Intracellular Bacteria for DNA Delivery
15.4.1 Starting Point: Delivering DNA Using Shigella flexneri
15.4.2 Gram-Positive Bacteria: Delivering DNA Using Listeria monocytogenes
15.4.3 Delivering DNA Using Salmonella typhimurium
15.5 Remaining Challenges and Strategies to Enhance Efficacy
15.6 Prospects
References
Chapter 16 Cytokines and Immune Modulatory Ligands as Gene Adjuvants
Translated by Chen Wei and Li Weizhong
16.1 Gene Adjuvants—Definition
16.2 Classification of Cytokines
16.3 Basic Characteristics and Biological Effects of Cytokines, Co-Stimulatory Molecules, and Other Immune Modulators
16.3.1 Interleukin
16.3.2 Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)
16.3.3 Interferon
16.3.4 Tumor Necrosis Factor (TNF) Family
16.3.5 Co-Stimulatory Factors
16.3.6 Immune Modulators
16.4 Effects of Cytokines and Immune Co-Stimulatory Molecules in Activating Immune Responses
16.5 Effects of Gene Adjuvants on Immune Responses to DNA Vaccines
16.5.1 Interleukin
16.5.2 Granulocyte-Macrophage Colony-Stimulating Factor
16.5.3 Interferon
16.5.4 TNF Family
16.5.5 Co-Stimulatory Molecules
16.5.6 Other Immune Modulators
16.6 Gene Adjuvant Transfer Modes
16.6.1 Immune Route
16.6.2 Transfer Mode
16.7 Transfer Dynamics
16.7.1 Effects of Gene Adjuvants in Prime-Boost Immunization Schemes
16.8 Summary
References
Chapter 17 Chemokines: Immune Modulators and Potential DNA Vaccine Adjuvants
Translated by Dong Shaozhong and Liu Longding
17.1 Abstract
17.2 Introduction
17.3 Background
17.3.1 Classification of the Chemokine System
17.3.2 Structure and Presentation of Chemokines
17.3.3 Regulatory Patterns of Chemokines
17.4 Regulation of the Immune System by Chemokines
17.4.1 Functional Classification of the Chemokine System
17.4.2 Effects of Chemokines on Immune System Development
17.4.3 Effects of Chemokines on Innate Immune Responses
17.4.4 Effects of Chemokines on Acquired Immune Responses
17.5 Application of Chemokines as Adjuvants for DNA Vaccines
17.6 Conclusion
References
Chapter 18 DNA Vaccines: Safety and Regulatory Issues
Translated by Jiang Li and Li Qihán
18.1 Abstract
18.2 The Danger of Plasmid Integration
18.3 Autoimmunity
18.4 Tolerance
18.5 Changes in the Immune Environment
18.6 Human Clinical Studies
18.7 Conclusion
References
Chapter 19 Promotion of New DNA Vaccines in Developing Countries
Translated by Wang Jingjing and Che Yanchun
19.1 Abstract
19.2 Introduction
19.3 Research and Development of Vaccines
19.3.1 New International Deployment
19.3.2 New Funding
19.3.3 Emerging Vaccine Producers in Developing Countries
19.4 Promotion Process
19.5 Establishing and Publishing Disease Burden Data and Cost-Effectiveness Calculations
19.6 Conducting Vaccine Promotion Trials and Efficacy Evaluations
19.7 Reaching International Consensus on Recommending Vaccines
19.8 Ensuring Sufficient and Cost-Competitive Vaccine Supply
19.8.1 Encouraging Competition
19.8.2 Retaining and Strengthening Vaccine Producers in Developing Countries
19.9 Creating a Funding Mechanism
19.10 Conclusion
References
Index