Vaccine Development: From Concept to Clinic

Cover
Dedication
Foreword
Contents
Chapter 1 Vaccine Development: From Concept to Clinic
1.1 Introduction
1.2 Preclinical Safety Assessment Considerations
1.3 Clinical Trials in the Development of Vaccines
1.5 High-throughput Assays for Clinical Development
1.6 Complexity in the Development of Multivalent Vaccines: Virus-like Particle-based Vaccines
1.7 Cell Culture-based Influenza Vaccine Development
1.8 Conjugate Vaccines: Design and Development Considerations
1.9 Vaccine Adjuvants
1.10 Development Considerations for Final Dosage Forms: Mucosal Bacterial Vaccines
1.11 Exploiting Glycans for Vaccine Design
1.12 Public–Private Partnerships for Vaccine Development
1.13 Structure-based Vaccine Design: The New Frontier
1.14 Vaccines to Target Antimicrobial Resistance
1.15 Technologies Revolutionizing Vaccines
1.15.1 Vaccines Based on Nucleic Acids
1.15.2 VLPs Produced from Plants
1.16 Vaccines Targeting Latent Viruses
1.16.1 Vaccines Targeting Shingles
1.16.2 Human Cytomegalovirus (CMV)
1.16.3 Epstein–Barr Virus (EBV)
1.17 The Unmet Medical Need
1.18 Herd Immunity
References
Chapter 2 Preclinical Safety Assessment Considerations for Vaccine Development
Introduction
2.2 General Considerations
2.2.1 Regulatory Guidelines for the Non-clinical Safety Assessment of Vaccines and Adjuvants
2.2.2 Vaccine Modalities
2.2.3 Antigen
2.2.4 Adjuvant
2.3 Vaccine Study Design
2.3.1 Test Article
2.3.2 Species Selection
2.3.3 Study Groups
2.3.4 Dose, Dose Volume, and Administration Location
2.3.5 Dose Number and Dosing Interval
2.3.6 In-life Assessments
2.3.7 Anatomical Pathology
2.4 Genotoxicity and Carcinogenicity Studies
2.5 Biodistribution Studies
2.6 Neurovirulence Studies
2.7 Reproductive Toxicology Studies
2.8 Conclusion
References
Chapter 3 Clinical Trials in the Development of Vaccines for Infectious Diseases
3.1 Types of Vaccines and Populations for Immunisation
3.2 Staging Clinical Trials Throughout a Development Programme
3.3 Immunogenicity
3.3.1 Types of Antibody Assay
3.3.2 How Antibody Values are Expressed
3.3.3 What Does an Antibody Response Mean?
3.3.4 CellularMethods for Assessing Immunogenicity
3.3.5 Limits to Blood Sample Volumes
3.3.6 Clinical Trials That Use Immunogenicity Endpoints
3.4 Efficacy
3.4.1 Defining Efficacy
3.4.2 Defining Cases Within an Efficacy Trial
3.4.3 Selection of Subjects for Efficacy Trials
3.4.4 Efficacy Study Design
3.4.5 Non-pivotal Efficacy Studies
3.4.6 Controlled Human Infection Models
3.5 Safety
3.5.1 Reactogenicity
3.5.2 Other Adverse Events
3.6 Conclusion
Postscript
References
Chapter 4 Clinical Trials in Immunotherapeutic Vaccine Development
4.1 Introduction
4.2 Considerations for Therapeutic Cancer Vaccine Clinical Trials
4.2.1 General Considerations
4.2.2 Early-phase Clinical Trials
4.2.3 Late-phase Clinical Trials
4.2.4 Recent Experiences with Cancer Vaccine Clinical Trials
4.3 Statistical Issues
4.4 Regulatory Considerations
4.5 Therapeutic Vaccine Research on Select Infectious and Other Non-communicable Diseases
4.5.1 HIV
4.5.2 Tuberculosis
4.5.3 Therapeutic Vaccination of Non-communicable Diseases
4.6 Conclusion
Acknowledgements
References
Chapter 5 Pathogenesis and Immunity of SARS-CoV-2 and Vaccination Programs Against COVID-19
5.1 Introduction
5.2 Structure and Viral Entry
5.3 Immune and Inflammatory Response to Infection
5.4 Current Approaches in Vaccine Design
5.4.1 Inactivated Vaccines
5.4.2 Non-replicating Viral Vector
5.4.3 Replicating Viral Vector
5.4.4 Protein Subunit
5.4.5 Virus-like Particles (VLPs)
5.4.6 Nucleic Acid
5.5 Other Therapeutic Strategies
5.6 SARS-CoV-2 Variant Strains
5.7 Conclusion and Perspectives
Acknowledgements
References
Chapter 6 High-throughput Assays for Clinical Development
6.1 Introduction
6.2 Glossary of Terms
6.3 Laboratory Robotics
6.3.1 Integration of Automated LaboratoryEquipment in the Regulated High-throughput Laboratory
6.3.2 Considerations for Selecting Robotic Systems
6.3.3 Qualification of Computer-driven Equipment for Laboratory Automation
6.3.4 Optimization of Robotic Liquid-handling Systems
6.3.5 Verifying Fluid Delivery of Robotic Liquid-handling Systems
6.4 Assay Development and Validation
6.4.1 Assay Development
6.4.2 Assay Validation
6.4.3 Role of Quality Control Samples in Assay Validation
6.4.4 Role of Assay Performance Acceptance Criteria in Assay Validation
6.5 Routine Maintenance of Validated Laboratory Methods
6.6 Sample-handling Procedures
6.6.1 Sample Tubes and Labels
6.6.2 Cold Chain and Sample Stability
6.6.3 Sample Shipping and Receiving
6.7 Inspection Readiness
6.7.1 Overall Condition of the Laboratory
6.7.2 Laboratory Access Control
6.7.3 Personnel Records
6.7.4 Proper Labeling
6.7.5 Equipment Maintenance Records
6.7.6 Control of Records
6.7.7 Document Version Control
6.7.8 Assay Long-term Performance Records
6.7.9 Good Documentation Practices
6.7.10 Expired Reagents
6.7.11 Change Control Procedures
6.7.12 Environmental Control Records
6.8 Conclusion
6.9 Further Reading
6.10 Regulatory Guidance
Chapter 7 Virus-like Particle-based Vaccines: GARDASIL®
7.1 Introduction
7.2 Early-stage Development
7.3 Late-stage Development
7.3.1 Improved Yield, Stability, and "Manufacturability"
7.3.2 Control of VLP Aggregation Approach 1: Fermentation Optimization
7.3.3 Control of VLP Aggregation Approach 2: VLP Reassembly
7.3.4 Control of VLP Aggregation Approach 3: Control of Polysorbate 80
7.3.5 Manufacturability
7.4 Conclusion
Abbreviations
References
Chapter 8 Cell Culture-based Influenza Vaccine Development
8.1 Potential Advantages of Cell Culture-based Influenza Vaccines
8.1.1 Disadvantages Associated with Egg-based Vaccines
8.1.2 Potential Advantages of Cell Culture-based Vaccines: Antigenic Match
8.1.3 Potential Advantages of Cell Culture-based Vaccines: Speed of Production
8.1.4 Potential Advantages of Cell Culture-based Vaccines: Production Capacity
8.2 Non-egg-based Influenza Vaccines
8.2.1 Flucelvax Quadrivalent Seasonal Influenza Vaccine
8.2.2 Flublok Quadrivalent Seasonal Influenza Vaccine
8.3 Non-egg-based Technologies in Development
Acknowledgements
References
Chapter 9 Conjugate Vaccines: Design and Development Considerations
9.1 Conjugate Vaccines: Background
9.2 Conjugate Vaccines to Curb Antimicrobial Resistance
9.3 Conjugate Vaccines for Maternal Immunization
9.4 Peptide-based Conjugate Vaccines
9.5 Glycoconjugate Vaccines
9.5.1 Carbohydrate Antigen Structure and Conformation
9.5.2 Anti-cancer Therapeutic Glycoconjugate Vaccine Antigens
9.6 Hapten–Protein Conjugates
Acknowledgements
References
Chapter 10 Vaccine Adjuvants: Mechanisms of Action
10.1 Introduction
10.2 The Innate Immune Response to Vaccines
10.3 Activation of Pattern Recognition Receptors by Adjuvants
10.4 Recruitment and Activation of Antigen-presenting Cells by Adjuvants
10.5 Transport of Antigen to the Draining Lymph Node
10.6 Effect of Adjuvants on Antigen Uptake and Presentation
10.7 Effect of Adjuvants on Lymphocyte Migration
10.8 Effect of Adjuvants on Germinal Center Formation
10.9 Future Directions
References
Chapter 11 Development Considerations for Final Dosage Forms: Mucosal Bacterial Vaccines
11.1 Types of Bacterial Vaccines
11.2 Vaccine Delivery Approaches
11.3 Oral Bacterial Vaccines
11.3.1 Advantage of Oral Route and MainBarriers to be Overcome to Deliver the Vaccine
11.3.2 Solid Oral Dosage Forms for Vaccines
11.3.3 Liquid and Semi-solid Oral Dosage Forms
11.4 Manufacturing Process for Finished Dosage-form Vaccines
11.4.1 Drying Bacteria by Lyophilization
11.4.2 Spray Drying Technology
11.4.3 Microencapsulation
11.5 Pediatric Dosage Forms: Challenges and Concerns
11.6 Conclusion and Perspectives
Note
References
Chapter 12 Exploiting Glycans in Vaccine Design
12.1 Introduction
12.2 Glycoconjugate Vaccines
12.2.1 Exploiting Additional Glycan Targets
12.3 Concluding Remarks
Acknowledgements
References
Chapter 13 The PATH Experience in Vaccine Development Partnerships with Manufacturers from Emerging Markets
13.1 Introduction
13.2 MenAfriVacs
13.2.1 Background
13.2.2 What Was the Genesis of the Project? Was There a "Tipping Point"?
13.2.3 What Roles Did Each Public and Private Partner Play?
13.2.4 Which Strategic Decisions Proved to Be Crucial for the Project's Success?
13.2.5 What Challenges Arose DuringDevelopment and How Were They Surmounted?
13.2.6 What Lasting Benefits Accrued to the Private Sector Partner?
13.2.7 Where Are We Today?
13.3 SIIPL PCV-10 (PNEUMOSIL®)
13.3.1 Background
13.3.2 What Was the Genesis of the Project? Was There a "Tipping Point"?
13.3.3 What Roles Did the Project's Public and Private Partners Play?
13.3.4 What Key Strategic Decisions Were MadeThat Proved to Be Crucial for the Success of the Project?
13.3.5 What Challenges Arose DuringDevelopment, and How Were They Surmounted?
13.3.6 Benefits to Private Sector Partners
13.3.7 Where Are We Today?
13.4 Japanese Encephalitis (Live Vaccine SA 14-14-2): CD.JEVAX®
13.4.1 Background
13.4.2 What Was the Genesis of the Project? Was There a "Tipping Point"?
13.4.3 What Were the Respective Roles of theDifferent Public and Private Partners, Including the Funder, in the Project?
13.4.4 What Key Strategic Decisions Were MadeThat Proved to Be Crucial for the Success of the Project?
13.4.5 What Challenges Arose During Development, and How Were They Surmounted?
13.4.6 What Other Benefits Accrued to the Public Sector Partner?
13.4.7 Where Are We Today?
13.5 Reflections
Acknowledgements
References
Subject Index