Chavda

Emerging Pathways of Vaccine Adjuvants

A Nonspecific Stimulant of the Immune System
Herausgeber: Chavda, Vivek P; Apostolopoulos, Vasso

• Gebundenes Buch

Produktbeschreibung

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. 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. 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.

Produktdetails

• Verlag: Wiley
• Seitenzahl: 288
• Erscheinungstermin: 4. Juni 2025
• Englisch
• Gewicht: 567g
• ISBN-13: 9781394237616
• ISBN-10: 1394237618
• Artikelnr.: 69605161

Autorenporträt

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.

Inhaltsangabe

Preface xv
1 Adjuvants Boosting Vaccine Effectiveness 1
Vasso Apostolopoulos
1.1 Vaccines Over the Years 1
1.2 Adjuvants in the Modern Era 2
1.3 Conventional Adjuvants 3
1.4 Particulate Adjuvants 5
1.5 Immunostimulatory Adjuvants 7
1.6 Approved Adjuvants for Human Use 8
1.7 Conclusion 9
References 10
2 In Silico Adjuvant Design and Validation for Vaccines 15
Vivek P. Chavda, Anjali P. Bedse, Pankti C. Balar, Bedanta Bhattacharjee,
Shilpa S. Raut and Vasso Apostolopoulos
2.1 Introduction 16
2.1.1 Importance of Vaccines and Adjuvants in Immunology 16
2.1.2 Limitations of Traditional Adjuvant Discovery Methods 16
2.1.3 Introduction to In Silico Approaches for Adjuvant Design 17
2.2 In Silico Techniques for Adjuvant Discovery 17
2.2.1 Immunoinformatics Tools for Epitope Prediction 18
2.2.1.1 Identification of B-Cell and T-Cell Epitopes 18
2.2.1.2 Tools Used for MHC and B-Cell Receptor Binding Prediction Tools 19
2.2.2 Molecular Docking Simulation 20
2.2.2.1 Application of Molecular Docking in Adjuvant Design 21
2.2.3 Artificial Intelligence and Machine Learning for Adjuvant Design 21
2.2.3.1 Leveraging Large Datasets for Adjuvant Discovery 22
2.2.3.2 Types of Machine Learning Algorithms Used 22
2.2.3.3 Case Study 23
2.2.4 In Silico Toxicology Prediction 23
2.2.4.1 Minimizing Safety Concerns During Adjuvant Design 24
2.2.4.2 Software Tools for Virtual Toxicity Assessment 24
2.3 Case Studies: Successful Applications of In Silico Adjuvant Design 25
2.3.1 Designing Adjuvants Targeting Specific Immune Pathways (e.g., TLR
Agonists) 25
2.3.2 Development of Multi-Epitope Vaccines with In Silico Adjuvant
Selection 27
2.3.3 Repurposing Existing Drugs as Vaccine Adjuvants Through In Silico
Analysis 28
2.4 Challenges and Future Directions of In Silico Adjuvant Design 29
2.5 Conclusion 31
References 32
3 Adjuvant and Immunity 39
Himel Mondal, Shaikat Mondal, Bairong Shen and Rajeev K. Singla
3.1 Introduction 40
3.2 Immune Response to Vaccines 42
3.2.1 Immune Response to Pathogens 42
3.2.2 Immune Response to Vaccines 44
3.3 Mechanisms of Adjuvants in Modulating Immunity 45
3.3.1 Sustained Release of Antigen 45
3.3.2 Upregulation of Cytokines and Chemokines 46
3.3.3 Cellular Recruitment at the Site of Injection 47
3.3.4 Increased Antigen Uptake and Presentation 47
3.3.5 Activation and Maturation of APCs 48
3.3.6 Activation of Inflammasomes 48
3.4 Immunogenicity According to the Types of Adjuvants 49
3.4.1 Minerals 49
3.4.2 Emulsions 50
3.4.3 Polymers 50
3.4.4 Saponins 51
3.4.5 Complement Components and Cytokines 52
3.4.6 Bacterial Components 52
3.5 Adjuvants and Humoral Immunity 53
3.5.1 B-Cell Activation and Antibody Production 53
3.5.2 Enhanced Germinal Center Formation 53
3.5.3 Isotype Switching 54
3.5.4 Long-Lasting Antibody Responses 54
3.5.5 Antibody Affinity Maturation 54
3.5.6 Enhanced IgG Subclass Responses 55
3.5.7 Increased Antibody Titers 55
3.6 Adjuvants and Cellular Immunity 56
3.6.1 Activation of Antigen-Presenting Cells (APCs) 56
3.6.2 Cytokine Production and T-Cell Differentiation 56
3.6.3 Cytotoxic T-Cell Activation 57
3.6.4 Cross-Presentation of Exogenous Antigens 57
3.6.5 Inflammation and Immune Cell Recruitment 57
3.6.6 Memory T-Cell Generation 57
3.6.7 Enhancement of Antigen Persistence 58
3.6.8 Antigen Depot Formation 58
3.6.9 Induction of Th1 Responses 58
3.7 Adjuvants and Innate Immunity 58
3.7.1 Phagocytosis and Antigen Processing 59
3.7.2 Complement Activation 59
3.7.3 Induction of Local Inflammation 59
3.7.4 Pattern Recognition Receptor Activation 60
3.7.5 Natural Killer (NK) Cell Activation 60
3.7.6 Activation of Epithelial Cells 60
3.8 Adjuvants and Mucosal Immunity 61
3.8.1 Enhanced Mucosal Antigen Uptake 61
3.8.2 Secretory IgA Production 62
3.8.3 Induction of Tolerance 62
3.8.4 Activation of Dendritic Cells 62
3.8.5 Recruitment of Effector Cells 62
3.8.6 Cross-Presentation at Mucosal Sites 63
3.8.7 Improvement of Oral and Nasal Vaccines 63
3.9 Adjuvants and Vaccine Efficacy in Specific Populations 63
3.9.1 Infant 64
3.9.2 Elderly 64
3.9.3 Immunocompromised Individuals 64
3.10 Conclusion 65
3.10.1 Enhanced Vaccine Efficacy 65
3.10.2 Tailored Immune Responses 66
3.10.3 Protection in Vulnerable Populations 66
3.10.4 Reduction in Antigen Doses 66
3.10.5 Development of Universal Vaccines 66
3.10.6 Management of Emerging Diseases 66
3.10.7 Prevention of Epidemics and Pandemics 66
3.10.8 Public Health Impact 67
References 67
4 Antigen Selection and Design 73
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 74
4.2 Types of Antigens Used in Vaccines 75
4.2.1 Whole Inactivated Pathogens 75
4.2.2 Live Attenuated Vaccine 76
4.2.3 Viral Subunit Vaccines 76
4.2.4 Conjugate Vaccines 77
4.2.5 DNA Vaccines 77
4.2.6 Other Antigen Types 78
4.2.7 Considerations for Antigen Selection 78
4.2.7.1 Specificity and Immunogenicity 78
4.2.7.2 Target Pathogen Life Cycle Stage 79
4.2.7.3 Safety and Stability 80
4.3 Antigen Design Strategies 80
4.3.1 Recombinant Protein Engineering (RPE) 80
4.3.1.1 Selection of Antigenic Regions 81
4.3.1.2 Gene Cloning 81
4.3.1.3 Vector Selection 81
4.3.1.4 Codon Optimization 81
4.3.1.5 Fusion Tags 81
4.3.1.6 Protein Refolding 81
4.3.1.7 Post-Translational Modifications 82
4.3.1.8 Structural Stabilization 82
4.3.1.9 Multimerization 82
4.3.2 Peptide Optimization 83
4.3.2.1 Identification of Immunogenic Epitopes 83
4.3.2.2 Selection of Conserved Regions 83
4.3.2.3 Length Optimization 83
4.3.2.4 Modification of Amino Acid Residues 83
4.3.2.5 Conjugation to Carrier Proteins 83
4.3.3 Reverse Vaccinology 84
4.3.3.1 Genome Sequencing 84
4.3.3.2 General Process Followed for Reverse Vaccinology Platform-Based
Modification 84
4.4 Adjuvants: Mechanism of Action and Types 85
4.4.1 The Rationale for Using Adjuvants 85
4.4.2 Mechanisms of Adjuvant Action 86
4.4.3 Types of Adjuvants 86
4.4.3.1 Aluminum Salts (Alum) 86
4.4.3.2 Toll-Like Receptor (TLR) Agonists 87
4.4.3.3 Saponins 88
4.4.3.4 Liposomes and Lipid-Based Nanoparticles (LNPs) 88
4.4.3.5 Polymer-Based Adjuvants 89
4.5 Novel Formulation Strategies for Improved Vaccine Efficacy 90
4.5.1 Biological Adjuvants 90
4.5.2 Biodegradable Polymers 93
4.5.3 Designer Adjuvants with Specific Immunomodulatory Properties 94
4.5.4 Adjuvanted Mucosal Vaccines 95
4.6 Future Directions and Challenges 96
4.6.1 Personalized Vaccines and Adjuvant Selection 96
4.6.2 Novel Adjuvant Discovery Platforms 97
4.6.3 Addressing Safety Concerns of New Adjuvants 97
4.7 Conclusion 97
References 98
5 Adjuvants in Licensed Vaccines 107
Kaushika Patel, Nandita Chawla, Yashvi Mehta and Sachin Patel
5.1 Introduction 108
5.2 Adjuvants Included in Vaccines 109
5.3 Cellular and Molecular Targets for Adjuvant 110
5.3.1 Depot Formation at the Injection Site 111
5.3.2 Induction and Upregulation of Cytokines and Chemokines 112
5.3.3 Antigen Presentation 112
5.3.4 Activation and Maturation of DCs 112
5.3.5 Activation of Inflammasomes 113
5.4 Endogenous Adjuvants in Live Vaccines 113
5.4.1 Alum 114
5.4.2 Aluminum-Based Adjuvants 115
5.4.3 Mf 59 117
5.4.4 Combination of Immune Stimulants: Adjuvant System (AS) 117
5.4.4.1 AS04 118
5.4.4.2 AS03 118
5.4.4.3 AS01 119
5.4.4.4 AS15 119
5.4.5 Cytosine Phosphoguanosine 1018 (CpG 1018) 120
5.4.5.1 Saponin-Based Adjuvants 120
5.4.5.2 Liposomal Adjuvants 121
5.4.6 Adjuvants for Coronavirus Vaccines 122
5.4.7 Cancer Vaccine Adjuvants 123
5.5 Vaccine Adjuvants in COVID-19 Vaccines 124
5.5.1 Reasons and the Advantages of Adjuvant Incorporation Into Vaccines
Against COVID- 19 125
5.5.2 Current Adjuvanted COVID-19 Vaccines 125
5.6 Adjuvant-Related Toxicities 127
5.6.1 Adjuvant-Associated Local Toxicity 127
5.6.2 Adjuvant-Associated Systemic Toxicity 127
5.7 Conclusion 128
References 128
6 Nanomaterial-Based Vaccine Adjuvants 137
Tanvi, Philips Kumar, Rajat Goyal, Kashish Wilson, Hitesh Chopra and Rajeev
K. Singla
6.1 Introduction 138
6.1.1 Unveiling the Essence: Navigating Vaccine Definition and
Conceptualizing Vaccines 138
6.1.1.1 Nanomaterials as Immune Modulators 139
6.1.1.2 Enhancing Efficacy and Safety 139
6.1.1.3 Personalized Vaccinology 139
6.1.2 Importance in Preventing Infectious Diseases 140
6.2 Vaccine Adjuvants and Their Role in Enhancing Immune Responses 141
6.2.1 Mechanism of Action 142
6.2.2 Types of Adjuvants 142
6.2.3 Need for Novel Adjuvants to Improve Vaccine Effectiveness and Safety
144
6.3 Overview of Nanotechnology and Introduction to Innovative Applications
in Medicines 145
6.3.1 Nanomaterials in Vaccines: Enhancing Immunity with Precision 147
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 148
6.4.1 Lipid Nanoparticles 148
6.4.2 Polymer Nanoparticles 148
6.4.3 Nanoparticles 148
6.4.4 Nanotubes 149
6.5 Engineered Nanomaterials as Vaccine Adjuvants 149
6.5.1 Metal and Metal Oxide Based Vaccine Adjuvant 150
6.5.1.1 Aluminum-Based Vaccine Adjuvant 150
6.5.1.2 Gold Nanoparticles 150
6.5.2 Polymeric Nanoparticles 151
6.5.2.1 Poly (Lactic-Co-Glycolic Acid) (PLGA) 151
6.5.2.2 Poly (¿-Glutamic Acid) (PGA) 152
6.5.2.3 Chitosan 152
6.5.2.4 Polyethyleneimine (PEI) 152
6.5.2.5 pH-Responsive Polymer 152
6.5.3 Liposome 153
6.5.4 Immune Activation Mechanism by ENMs 153
6.6 Challenges in the Development of ENM-Based Adjuvants 155
6.7 Mechanism of Action and Data 156
6.7.1 Interactions of Nanomaterial-Based Adjuvants with the Immune System
for Enhanced Vaccine Response 157
6.8 Case Studies: Examples of Nanomaterial-Based Adjuvants 158
6.8.1 Nanomaterial-Enhanced Vaccines: Insights from Preclinical and
Clinical Studies 159
6.8.2 Advantages and Challenges Associated with Each Nanomaterial 160
6.9 Design and Development Considerations 160
6.9.1 Navigating Nanomaterial-Based Adjuvant Design: Balancing
Manufacturing Scalability, Stability, and Regulatory Compliance 161
6.9.2 Importance of Balancing Immunostimulants with Safety to Avoid Adverse
Reactions 162
6.10 Future Perspectives and Challenge 163
6.10.1 Advancing Nanomaterial-Based Adjuvants: Pioneering Personalized
Vaccines and Synergistic Combination Strategies 163
6.10.2 Navigating Nanomaterial-Based Adjuvant Development: Overcoming
Toxicity Concerns and Regulatory Challenges 164
6.11 Conclusion 165
References 166
7 Adjuvants for Non-Invasive Routes of Vaccine Delivery 171
Shruti U. Rawal, Tosha Pandya, Mangesh Kulkarni, Riya Patel and Anjali
Menon
7.1 Introduction 172
7.2 Vaccine Delivery Through Non-Invasive Routes: Scopes and Challenges 175
7.2.1 Mucosal Delivery: Oral, Buccal, Sublingual, Intranasal, Pulmonary,
Rectal, and Vaginal Delivery 177
7.2.2 Intradermal and Transdermal Delivery 179
7.2.3 Ocular Delivery 180
7.3 Conventional and Novel Adjuvants 181
7.3.1 Conventional Adjuvants 182
7.3.2 Novel Adjuvants 183
7.3.2.1 Liposomes and Niosomes 187
7.3.2.2 Virus-Like Particles (VLPs) and Virosomes 188
7.3.2.3 Lipid-Based Nanoparticles 189
7.3.2.4 Nanoemulsions (NEs) 190
7.3.2.5 Dendrimers 190
7.3.2.6 Polymeric Nanoparticles 191
7.3.2.7 Miscellaneous Novel Adjuvants 191
7.3.3 Recent Novel Adjuvants 192
7.3.3.1 Archaeosomes 192
7.3.3.2 Proteosomes 192
7.3.3.3 Carbonate Apatite Nanoparticles 193
7.3.3.4 Hyaluronan Nanocarriers and Laser Adjuvant 193
7.3.3.5 Nanoparticles Containing DNA Vaccine pRSC-gD-IL- 21 194
7.3.3.6 Glucopyranosyl Lipid A (GLA) as Immune Adjuvant for Respirable
HPV-L2 Dry Powder Vaccine 194
7.4 Toxicity and Adverse Events 195
7.4.1 Systemic Reactogenicity and Reactions 195
7.5 Regulatory Approval for Adjuvants and Adjuvanted Vaccines 196
7.5.1 Challenges for Safety Evaluation of Adjuvanated Vaccines 200
7.5.2 Challenges During Pre-Clinical Phase 200
7.6 Prospects 200
7.7 Conclusion 201
References 202
8 Regulatory Guidelines for Vaccine Adjuvants 211
Suneetha Vuppu, Vivek P. Chavda, Toshika Mishra, Nikita Sharma and Sathvika
Kamaraj
8.1 Introduction 212
8.2 Vaccine Adjuvants 214
8.3 Mechanism of Action 215
8.3.1 Formation of Depot for Antigen Protection 216
8.3.2 Enhanced Presentation of Antigen 216
8.3.3 Modulation of Immune Response 216
8.4 Adjuvant Platforms 219
8.5 Regulatory Guidelines for Vaccine Adjuvants 221
8.5.1 World Health Organization 223
8.5.2 Food and Drug Administration 224
8.5.3 European Medicines Agency 225
8.5.4 Health Canada 226
8.5.5 Australian Therapeutic Goods Administration (TGA) 227
8.6 Conclusion 227
Acknowledgments 227
References 228
9 Adjuvant and Vaccine Safety 235
Shalini Bhattacharya, Jyoti Singh, Rupesh K. Gautam, Nadeem Farooqui,
Nimita Manocha and Hitesh Malhotra
9.1 Introduction 235
9.1.1 Classification of Adjuvants 237
9.1.1.1 Aluminum Salts 237
9.1.1.2 Liposomal Adjuvants 238
9.1.1.3 Emulsion-Based Adjuvants 238
9.1.1.4 Virus-Like Particle Adjuvant 238
9.1.1.5 Saponin-Based Adjuvant 239
9.2 Method and Mechanism of Action 245
9.3 Approaches and Perceptions of Adjuvant Safety in Public Health 247
9.3.1 Preclinical Safety Evaluation of Adjuvants 247
9.3.2 Adjuvants' Clinical Safety Evaluation 248
9.3.2.1 Phase I Clinical Trials 248
9.3.2.2 II/III Phase Clinical Trials 249
9.3.2.3 Post-Marketing Surveillance 249
9.4 Guidelines and Regulatory Considerations 249
9.5 Adjuvant Safety Testing With Emerging Technologies 250
9.6 Conclusion 251
References 252
10 Shortcomings of Current Adjuvants and Future Prospects 255
Pankti C. Balar, Vasso Apostolopoulos and Vivek P. Chavda
10.1 Introduction 256
10.2 Limitations 256
10.3 Advancements 257
10.4 This Book 259
10.5 The Future 259
References 260
Index 263