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Emerging Pathways of Vaccine Adjuvants

A Nonspecific Stimulant of the Immune System

Edited by Vivek P. Chavda and Vasso Apostolopoulos
Copyright: 2025   |   Expected Pub Date:2025/01/30
ISBN: 9781394237616  |  Hardcover  |  
282 pages

One Line Description
The book presents invaluable insights into the latest advancements, challenges, and research on vaccine adjuvants, which are key to developing more effective and safer vaccines essential for tackling pressing global health challenges.

Audience
Researchers and pharmacy students in biomedical engineering and chemical engineering, biotechnology, as well as pharmaceutical and biopharmaceutical industry engineers working in drug discovery, chemical biology, computational chemistry, medicinal chemistry, and bioinformatics.

Description
Emerging Pathways of Vaccine Adjuvants: A Nonspecific Stimulant of the Immune System aims to drive progress in vaccine research, paving the way for the development of more potent and safer vaccines to address global health threats. This volume provides a comprehensive overview of the evolving landscape of vaccine adjuvants, encompassing a wide range of topics critical to their design, development, and application. Adjuvants play a crucial role in vaccine formulations by boosting the immunogenicity of antigens, thereby enhancing vaccine efficacy. While antigens can initiate immune responses independently, adjuvants amplify these responses. Extensive research efforts are focused on the formulation of adjuvants to establish accurate, efficient, and safe manufacturing techniques. This book provides a clear explanation of the strict regulatory issues, making it an essential resource for students, businesspeople, and academics across the globe.
Readers will find the book:
•Encompasses current adjuvant usage and possible tactics to ensure effective production and delivery of the active constituent;
•Presents challenges and innovations with implications to provide cheaper, more efficient solutions in the industry;
•Prepares students for work in the industry, refining their skills for the production of critical medications.

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Author / Editor Details
Vivek P. Chavda is an assistant professor in the Department of Pharmaceutics and Pharmaceutical Technology, L.M. College of Pharmacy, Gujarat, India with over eight years of teaching and biologics industry experience. He has more than 200 national and international publications, four edited books, an authored book, and 28 book chapters and is working on three patents. His research interests include the development of biologics processes and formulations, medical device development, nanodiagnostics and non-carrier formulations, long-acting parenteral formulations, and nanovaccines.

Vasso Apostolopoulos, PhD, is a Vice-Chancellor Distinguished Fellow and Director of the Immunology and Translational Research Group at Victoria University, Australia and the Immunology Program Director at the Australian Institute for Musculoskeletal Science, Australia. She is a world-renowned researcher with over 100 awards, 510 research publications, and 22 patents to her credit. Her interests include vaccine and drug development for cancer, chronic, infectious, and autoimmune diseases.

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Table of Contents
Preface
1. Adjuvants Boosting Vaccine Effectiveness
Vasso Apostolopoulos
1.1 Vaccines Over the Years
1.2 Adjuvants in the Modern Era
1.3 Conventional Adjuvants
1.4 Particulate Adjuvants
1.5 Immunostimulatory Adjuvants
1.6 Approved Adjuvants for Human Use
1.7 Conclusion
References
2. In Silico Adjuvant Design and Validation for Vaccines
Vivek P. Chavda, Anjali P. Bedse, Pankti C. Balar, Bedanta Bhattacharjee, Shilpa S. Raut and Vasso Apostolopoulos
2.1 Introduction
2.1.1 Importance of Vaccines and Adjuvants in Immunology
2.1.2 Limitations of Traditional Adjuvant Discovery Methods
2.1.3 Introduction to In Silico Approaches for Adjuvant Design
2.2 In Silico Techniques for Adjuvant Discovery
2.2.1 Immunoinformatics Tools for Epitope Prediction
2.2.1.1 Identification of B-Cell and T-Cell Epitopes
2.2.1.2 Tools Used for MHC and B-Cell Receptor Binding Prediction Tools
2.2.2 Molecular Docking Simulation
2.2.2.1 Application of Molecular Docking in Adjuvant Design
2.2.3 Artificial Intelligence and Machine Learning for Adjuvant Design
2.2.3.1 Leveraging Large Datasets for Adjuvant Discovery
2.2.3.2 Types of Machine Learning Algorithms Used
2.2.3.3 Case Study
2.2.4 In Silico Toxicology Prediction
2.2.4.1 Minimizing Safety Concerns During Adjuvant Design
2.2.4.2 Software Tools for Virtual Toxicity Assessment
2.3 Case Studies: Successful Applications of In Silico Adjuvant Design
2.3.1 Designing Adjuvants Targeting Specific Immune Pathways (e.g., TLR Agonists)
2.3.2 Development of Multi-Epitope Vaccines with In Silico Adjuvant Selection
2.3.3 Repurposing Existing Drugs as Vaccine Adjuvants Through In Silico Analysis
2.4 Challenges and Future Directions of In Silico Adjuvant Design
2.5 Conclusion
References
3. Adjuvant and Immunity
Himel Mondal, Shaikat Mondal, Bairong Shen and Rajeev K. Singla
3.1 Introduction
3.2 Immune Response to Vaccines
3.2.1 Immune Response to Pathogens
3.2.2 Immune Response to Vaccines
3.3 Mechanisms of Adjuvants in Modulating Immunity
3.3.1 Sustained Release of Antigen
3.3.2 Upregulation of Cytokines and Chemokines
3.3.3 Cellular Recruitment at the Site of Injection
3.3.4 Increased Antigen Uptake and Presentation
3.3.5 Activation and Maturation of APCs
3.3.6 Activation of Inflammasomes
3.4 Immunogenicity According to the Types of Adjuvants
3.4.1 Minerals
3.4.2 Emulsions
3.4.3 Polymers
3.4.4 Saponins
3.4.5 Complement Components and Cytokines
3.4.6 Bacterial Components
3.5 Adjuvants and Humoral Immunity
3.5.1 B-Cell Activation and Antibody Production
3.5.2 Enhanced Germinal Center Formation
3.5.3 Isotype Switching
3.5.4 Long-Lasting Antibody Responses
3.5.5 Antibody Affinity Maturation
3.5.6 Enhanced IgG Subclass Responses
3.5.7 Increased Antibody Titers
3.6 Adjuvants and Cellular Immunity
3.6.1 Activation of Antigen-Presenting Cells (APCs)
3.6.2 Cytokine Production and T-Cell Differentiation
3.6.3 Cytotoxic T-Cell Activation
3.6.4 Cross-Presentation of Exogenous Antigens
3.6.5 Inflammation and Immune Cell Recruitment
3.6.6 Memory T-Cell Generation
3.6.7 Enhancement of Antigen Persistence
3.6.8 Antigen Depot Formation
3.6.9 Induction of Th1 Responses
3.7 Adjuvants and Innate Immunity
3.7.1 Phagocytosis and Antigen Processing
3.7.2 Complement Activation
3.7.3 Induction of Local Inflammation
3.7.4 Pattern Recognition Receptor Activation
3.7.5 Natural Killer (NK) Cell Activation
3.7.6 Activation of Epithelial Cells
3.8 Adjuvants and Mucosal Immunity
3.8.1 Enhanced Mucosal Antigen Uptake
3.8.2 Secretory IgA Production
3.8.3 Induction of Tolerance
3.8.4 Activation of Dendritic Cells
3.8.5 Recruitment of Effector Cells
3.8.6 Cross-Presentation at Mucosal Sites
3.8.7 Improvement of Oral and Nasal Vaccines
3.9 Adjuvants and Vaccine Efficacy in Specific Populations
3.9.1 Infant
3.9.2 Elderly
3.9.3 Immunocompromised Individuals
3.10 Conclusion
3.10.1 Enhanced Vaccine Efficacy
3.10.2 Tailored Immune Responses
3.10.3 Protection in Vulnerable Populations
3.10.4 Reduction in Antigen Doses
3.10.5 Development of Universal Vaccines
3.10.6 Management of Emerging Diseases
3.10.7 Prevention of Epidemics and Pandemics
3.10.8 Public Health Impact
References
4. Antigen Selection and Design
Pankti C. Balar, Anjali P. Bedse, Vivek P. Chavda, Chukwuebuka E. Umeyor, Prafull Kolekar, Brian O. Ogbonna, Ankita Anure, Daniel U. Eze, Payal Dodiya and Vandana B. Patravale
4.1 Introduction
4.2 Types of Antigens Used in Vaccines
4.2.1 Whole Inactivated Pathogens
4.2.2 Live Attenuated Vaccine
4.2.3 Viral Subunit Vaccines
4.2.4 Conjugate Vaccines
4.2.5 DNA Vaccines
4.2.6 Other Antigen Types
4.2.7 Considerations for Antigen Selection
4.2.7.1 Specificity and Immunogenicity
4.2.7.2 Target Pathogen Life Cycle Stage
4.2.7.3 Safety and Stability
4.3 Antigen Design Strategies
4.3.1 Recombinant Protein Engineering (RPE)
4.3.1.1 Selection of Antigenic Regions
4.3.1.2 Gene Cloning
4.3.1.3 Vector Selection
4.3.1.4 Codon Optimization
4.3.1.5 Fusion Tags
4.3.1.6 Protein Refolding
4.3.1.7 Post-Translational Modifications
4.3.1.8 Structural Stabilization
4.3.1.9 Multimerization
4.3.2 Peptide Optimization
4.3.2.1 Identification of Immunogenic Epitopes
4.3.2.2 Selection of Conserved Regions
4.3.2.3 Length Optimization
4.3.2.4 Modification of Amino Acid Residues
4.3.2.5 Conjugation to Carrier Proteins
4.3.3 Reverse Vaccinology
4.3.3.1 Genome Sequencing
4.3.3.2 General Process Followed for Reverse Vaccinology Platform-Based Modification
4.4 Adjuvants: Mechanism of Action and Types
4.4.1 The Rationale for Using Adjuvants
4.4.2 Mechanisms of Adjuvant Action
4.4.3 Types of Adjuvants
4.4.3.1 Aluminum Salts (Alum)
4.4.3.2 Toll-Like Receptor (TLR) Agonists
4.4.3.3 Saponins
4.4.3.4 Liposomes and Lipid-Based Nanoparticles (LNPs)
4.4.3.5 Polymer-Based Adjuvants
4.5 Novel Formulation Strategies for Improved Vaccine Efficacy
4.5.1 Biological Adjuvants
4.5.2 Biodegradable Polymers
4.5.3 Designer Adjuvants with Specific Immunomodulatory Properties
4.5.4 Adjuvanted Mucosal Vaccines
4.6 Future Directions and Challenges
4.6.1 Personalized Vaccines and Adjuvant Selection
4.6.2 Novel Adjuvant Discovery Platforms
4.6.3 Addressing Safety Concerns of New Adjuvants
4.7 Conclusion
References
5. Adjuvants in Licensed Vaccines
Kaushika Patel, Nandita Chawla, Yashvi Mehta and Sachin Patel
5.1 Introduction
5.2 Adjuvants Included in Vaccines
5.3 Cellular and Molecular Targets for Adjuvant
5.3.1 Depot Formation at the Injection Site
5.3.2 Induction and Upregulation of Cytokines and Chemokines
5.3.3 Antigen Presentation
5.3.4 Activation and Maturation of DCs
5.3.5 Activation of Inflammasomes
5.4 Endogenous Adjuvants in Live Vaccines
5.4.1 Alum
5.4.2 Aluminum-Based Adjuvants
5.4.3 MF59
5.4.4 Combination of Immune Stimulants: Adjuvant System (AS)
5.4.4.1 AS04
5.4.4.2 AS03
5.4.4.3 AS01
5.4.4.4 AS15
5.4.5 Cytosine Phosphoguanosine 1018 (CpG 1018)
5.4.5.1 Saponin-Based Adjuvants
5.4.5.2 Liposomal Adjuvants
5.4.6 Adjuvants for Coronavirus Vaccines
5.4.7 Cancer Vaccine Adjuvants
5.5 Vaccine Adjuvants in COVID-19 Vaccines
5.5.1 Reasons and the Advantages of Adjuvant Incorporation Into Vaccines Against COVID-19
5.5.2 Current Adjuvanted COVID-19 Vaccines
5.6 Adjuvant-Related Toxicities
5.6.1 Adjuvant-Associated Local Toxicity
5.6.2 Adjuvant-Associated Systemic Toxicity
5.7 Conclusion
References
6. Nanomaterial-Based Vaccine Adjuvants
Tanvi, Philips Kumar, Rajat Goyal, Kashish Wilson, Hitesh Chopra and Rajeev K. Singla
6.1 Introduction
6.1.1 Unveiling the Essence: Navigating Vaccine Definition and Conceptualizing Vaccines
6.1.1.1 Nanomaterials as Immune Modulators
6.1.1.2 Enhancing Efficacy and Safety
6.1.1.3 Personalized Vaccinology
6.1.2 Importance in Preventing Infectious Diseases
6.2 Vaccine Adjuvants and Their Role in Enhancing Immune Responses
6.2.1 Mechanism of Action
6.2.2 Types of Adjuvants
6.2.3 Need for Novel Adjuvants to Improve Vaccine Effectiveness and Safety
6.3 Overview of Nanotechnology and Introduction to Innovative Applications in Medicines
6.3.1 Nanomaterials in Vaccines: Enhancing Immunity with Precision
6.4 Exploring the Nano Realm: Properties and Varied Types of Nanomaterials in Vaccines or Exploring Nanomaterials in Vaccines: Properties, Types, and Implications for Immunization
6.4.1 Lipid Nanoparticles
6.4.2 Polymer Nanoparticles
6.4.3 Nanoparticles
6.4.4 Nanotubes
6.5 Engineered Nanomaterials as Vaccine Adjuvants
6.5.1 Metal and Metal Oxide Based Vaccine Adjuvant
6.5.1.1 Aluminum-Based Vaccine Adjuvant
6.5.1.2 Gold Nanoparticles
6.5.2 Polymeric Nanoparticles
6.5.2.1 Poly (Lactic-Co-Glycolic Acid) (PLGA)
6.5.2.2 Poly (γ-Glutamic Acid) (PGA)
6.5.2.3 Chitosan 1
6.5.2.4 Polyethyleneimine (PEI)
6.5.2.5 pH-Responsive Polymer
6.5.3 Liposome
6.5.4 Immune Activation Mechanism by ENMs
6.6 Challenges in the Development of ENM-Based Adjuvants
6.7 Mechanism of Action and Data
6.7.1 Interactions of Nanomaterial-Based Adjuvants with the Immune System for Enhanced Vaccine Response
6.8 Case Studies: Examples of Nanomaterial-Based Adjuvants
6.8.1 Nanomaterial-Enhanced Vaccines: Insights from Preclinical and Clinical Studies
6.8.2 Advantages and Challenges Associated with Each Nanomaterial
6.9 Design and Development Considerations
6.9.1 Navigating Nanomaterial-Based Adjuvant Design: Balancing Manufacturing Scalability, Stability, and Regulatory Compliance
6.9.2 Importance of Balancing Immunostimulants with Safety to Avoid Adverse Reactions
6.10 Future Perspectives and Challenge
6.10.1 Advancing Nanomaterial-Based Adjuvants: Pioneering Personalized Vaccines and Synergistic Combination Strategies
6.10.2 Navigating Nanomaterial-Based Adjuvant Development: Overcoming Toxicity Concerns and Regulatory Challenges
6.11 Conclusion
References
7. Adjuvants for Non-Invasive Routes of Vaccine Delivery
Shruti U. Rawal, Tosha Pandya, Mangesh Kulkarni, Riya Patel and Anjali Menon
7.1 Introduction
7.2 Vaccine Delivery Through Non-Invasive Routes: Scopes and Challenges
7.2.1 Mucosal Delivery: Oral, Buccal, Sublingual, Intranasal, Pulmonary, Rectal, and Vaginal Delivery
7.2.2 Intradermal and Transdermal Delivery
7.2.3 Ocular Delivery
7.3 Conventional and Novel Adjuvants
7.3.1 Conventional Adjuvants
7.3.2 Novel Adjuvants
7.3.2.1 Liposomes and Niosomes
7.3.2.2 Virus-Like Particles (VLPs) and Virosomes
7.3.2.3 Lipid-Based Nanoparticles
7.3.2.4 Nanoemulsions (NEs)
7.3.2.5 Dendrimers
7.3.2.6 Polymeric Nanoparticles
7.3.2.7 Miscellaneous Novel Adjuvants
7.3.3 Recent Novel Adjuvants
7.3.3.1 Archaeosomes
7.3.3.2 Proteosomes
7.3.3.3 Carbonate Apatite Nanoparticles
7.3.3.4 Hyaluronan Nanocarriers and Laser Adjuvant
7.3.3.5 Nanoparticles Containing DNA Vaccine pRSC-gD-IL-21
7.3.3.6 Glucopyranosyl Lipid A (GLA) as Immune Adjuvant for Respirable HPV-L2 Dry Powder Vaccine
7.4 Toxicity and Adverse Events
7.4.1 Systemic Reactogenicity and Reactions
7.5 Regulatory Approval for Adjuvants and Adjuvanted Vaccines
7.5.1 Challenges for Safety Evaluation of Adjuvanated Vaccines
7.5.2 Challenges During Pre-Clinical Phase
7.6 Prospects
7.7 Conclusion
References
8. Regulatory Guidelines for Vaccine Adjuvants
Suneetha Vuppu, Vivek P. Chavda, Toshika Mishra, Nikita Sharma and Sathvika Kamaraj
8.1 Introduction
8.2 Vaccine Adjuvants
8.3 Mechanism of Action
8.3.1 Formation of Depot for Antigen Protection
8.3.2 Enhanced Presentation of Antigen
8.3.3 Modulation of Immune Response
8.4 Adjuvant Platforms
8.5 Regulatory Guidelines for Vaccine Adjuvants
8.5.1 World Health Organization
8.5.2 Food and Drug Administration
8.5.3 European Medicines Agency
8.5.4 Health Canada
8.5.5 Australian Therapeutic Goods Administration (TGA)
8.6 Conclusion
Acknowledgments
References
9. Adjuvant and Vaccine Safety
Shalini Bhattacharya, Jyoti Singh, Rupesh K. Gautam, Nadeem Farooqui, Nimita Manocha and Hitesh Malhotra
9.1 Introduction
9.1.1 Classification of Adjuvants
9.1.1.1 Aluminum Salts
9.1.1.2 Liposomal Adjuvants
9.1.1.3 Emulsion-Based Adjuvants
9.1.1.4 Virus-Like Particle Adjuvant
9.1.1.5 Saponin-Based Adjuvant
9.2 Method and Mechanism of Action
9.3 Approaches and Perceptions of Adjuvant Safety in Public Health
9.3.1 Preclinical Safety Evaluation of Adjuvants
9.3.2 Adjuvants’ Clinical Safety Evaluation
9.3.2.1 Phase I Clinical Trials
9.3.2.2 II/III Phase Clinical Trials
9.3.2.3 Post-Marketing Surveillance
9.4 Guidelines and Regulatory Considerations
9.5 Adjuvant Safety Testing With Emerging Technologies
9.6 Conclusion
References
10. Shortcomings of Current Adjuvants and Future Prospects
Pankti C. Balar, Vasso Apostolopoulos and Vivek P. Chavda
10.1 Introduction
10.2 Limitations
10.3 Advancements
10.4 This Book
10.5 The Future
References
Index

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