Preface xv 1 Introduction to Viral Vectors 1 Anjali P. Bedse, Suchita P. Dhamane, Shilpa S. Raut, Komal P. Mahajan and Kajal P. Baviskar 1.1 Introduction 2 1.2 Baculovirus Vectors 3 1.
3 Adenovirus Vectors 4 1.4 Poxvirus Vectors 6 1.5 Herpes Virus Vectors 8 1.6 Epstein-Barr Virus Vectors 9 1.7 Retrovirus Vectors 10 1.8 Lentivirus Vectors 11 1.9 Adeno-Associated Virus (AAV) 13 1.10 Applications of Viral Vectors 14 1.
10.1 Viral Vectors for Vaccine Development 14 1.10.2 Gene Therapy: The Performance of Viral Vectors 15 1.10.3 Clinical Trials 15 1.11 Safety Issues of Viral Vector/Biosafety Challenges 16 1.12 Conclusion 18 References 19 2 Viral Vector Construction 25 Suneetha Vuppu, Toshika Mishra, Shatakshi Mishra, Stany B.
and Anushka Das 2.1 Introduction 26 2.2 Applications of Viral Vector 27 2.3 Viral Vectors 29 2.3.1 Adenoviruses 29 2.3.2 Retroviruses 35 2.
3.3 Lentiviruses 36 2.3.4 Poxviruses 36 2.3.5 Adeno-Associated Viruses 37 2.3.6 Herpes Simplex Viruses 38 2.
3.7 Alphaviruses 39 2.3.8 Flaviviruses 39 2.3.9 Rhabdoviruses 40 2.3.10 Newcastle Disease Virus 40 2.
3.11 Coxsackieviruses 41 2.3.12 Measles Virus 41 2.4 Construction of Viral Vectors 42 2.5 Challenges 46 2.5.1 Immune Response 46 2.
5.2 Specificity of the Transgene Delivery 47 2.5.3 Insertional Mutagenesis 48 2.6 Advancements in Technology of Viral Vector Construction 49 2.7 Conclusion and Future Prospects 51 Acknowledgments 53 References 53 3 The Role of Adjuvants in the Application of Viral Vector Vaccines 65 Vivek P. Chavda, Anjali P. Bedse and Shilpa S.
Raut 3.1 Introduction 66 3.2 Viral Vector Vaccines: A Powerful Platform 67 3.3 Challenges Associated with Viral Vector Vaccines 69 3.3.1 Preexisting Immunity against the Viral Vector 69 3.3.2 Safety Concerns Related to Insertional Mutagenesis 70 3.
3.3 Scalability and Manufacturing Challenges 72 3.4 The Role of Adjuvants in Overcoming Challenges 72 3.4.1 Mechanisms of Action of Adjuvants 72 3.4.2 Innate Immune Stimulation 73 3.4.
3 Adaptive Immune Response Enhancement 73 3.4.4 Different Classes of Adjuvants Used with Viral Vector Vaccines 74 3.4.4.1 Classes of Adjuvants 74 3.4.5 Targeting CLR Pathway 75 3.
4.6 Saponins 75 3.4.7 Cytokines and Chemokines 76 3.4.8 Case Studies of Specific Adjuvants Used with Viral Vector Vaccines 76 3.5 Optimizing Adjuvant Design for Viral Vector Vaccines 76 3.5.
1 Importance of Adjuvant Selection and Formulation 76 3.5.2 Adjuvant Formulation Development 77 3.5.3 Adjuvant Formulations for the Development of New Vaccines 77 3.5.4 Strategies for Optimizing Adjuvant Design 78 3.5.
4.1 Dose Sparing 78 3.5.4.2 Enabling a More Rapid Immune Response 78 3.5.4.3 Antibody Response Broadening 78 3.
5.4.4 Antibody Response Magnitude and Functionality 79 3.5.5 Delivery Systems 79 3.5.5.1 Targeting Specific Immune Cell Populations 79 3.
5.5.2 Combination Adjuvants 79 3.5.5.3 Challenges and Future Directions in Adjuvant Development for Viral Vector Vaccines 80 3.6 Conclusion 80 References 81 4 Replication-Competent Viral Vectors for Vaccine Delivery 91 Vivek P. Chavda, Pankti C.
Balar, Dixa A. Vaghela, Divya Teli, Amit Chaudhari and Shahnaz Alom 4.1 Introduction 92 4.2 Types of Replication-Competent Viral Vectors 93 4.2.1 Adenoviruses (AdVs) 93 4.2.2 Vesicular Stomatitis Viruses (VSVs) 93 4.
2.3 Modified Vaccinia Ankara (MVA) 94 4.2.4 Measles Virus (MV) 94 4.2.5 Influenza Virus (IV) 95 4.3 Mechanisms of RCVV-Mediated Vaccination 97 4.4 Applications of Replication-Competent Viral Vectors 101 4.
4.1 Prophylactic Vaccines 101 4.4.2 Therapeutic Vaccines 102 4.4.2.1 Vesicular Stomatitis Virus 102 4.4.
2.2 Cytomegalovirus 103 4.4.2.3 Measles Virus 104 4.4.2.4 Adenoviral Vectors 104 4.
4.2.5 Applications of Replication-Competent Viral Vectors against COVID- 19 105 4.4.3 Cancer Immunotherapy 111 4.5 Conclusion 115 References 116 5 Nonreplicating Viral Vectors for Vaccine Delivery 125 Pankti C. Balar and Vivek P. Chavda 5.
1 Introduction 126 5.2 Nonreplicating Viral Vectors: Types and Characteristics 127 5.2.1 Adenoviral Vectors 127 5.2.2 Non-Adenoviral Vectors 128 5.2.3 Key Characteristics of Nonreplicating Vectors 129 5.
2.3.1 Immunogenicity 129 5.2.3.2 Safety 130 5.2.3.
3 Stability 131 5.2.3.4 Targeted Delivery 131 5.3 Engineering Nonreplicating Viral Vectors for Vaccine Design 132 5.3.1 Capsid Modification 132 5.3.
2 Promoter Engineering 133 5.3.3 Transgene Optimization 134 5.3.4 Immune Evasion Strategies 134 5.4 Applications of Nonreplicating Viral Vectors in Vaccinology 136 5.5 Optimizing Nonreplicating Viral Vectors for Vaccine Delivery 138 5.5.
1 Enhancing Transduction Efficiency 138 5.5.2 Reducing Immunogenicity and Toxicity 139 5.5.3 Improving Antigen Expression and Presentation 139 5.5.4 Addressing Preexisting Immunity 140 5.5.
5 Targeting Vector Delivery to Secondary Lymphoid Organs 141 5.6 Challenges and Future Perspectives 141 5.7 Conclusion 143 References 144 6 Genetically Modified Viral Vectors for Vaccine Delivery 149 Deepshi Arora, Yugam Taneja, Diksha Gulati, Manish Kumar, Anil Pareek and Rupesh K. Gautam 6.1 Introduction 150 6.2 Genetic Modification of Viral Vectors 153 6.3 Applications of Genetically Modified Viral Vectors 155 6.4 Administration of Vaccines 159 6.
5 Immune Response and Protection 161 6.6 Case Studies 163 6.7 Challenges and Future Directions 165 6.8 Conclusion 168 References 171 7 DNA- and RNA-Based Viral Vectors 179 Devesh U. Kapoor, Bhumi Bhatt, Dipansu Sahu, Rajiv R. Kakkar, Sonam M. Gandhi and Rupesh K. Gautam 7.
1 Introduction to Viral Vectors 180 7.1.1 Definition and Overview 180 7.1.2 Importance in Vaccine Delivery and Vaccination 180 7.2 Basics of Deoxyribonucleic Acid (DNA) and Ribonucleic Acid (RNA) Viruses 180 7.2.1 Structure and Replication of DNA Viruses 181 7.
2.2 Structure and Replication of RNA Viruses 181 7.2.3 Characteristics Relevant to Vector Development 182 7.2.3.1 Plasmids 182 7.2.
3.2 Viral Vectors 183 7.2.3.3 Artificial Chromosomes 183 7.3 DNA-Based Viral Vectors 183 7.3.1 Adenoviral Vectors 183 7.
3.1.1 Advantages and Limitations of Adenoviral Vectors 185 7.3.1.2 Adenoviral Vectors Applications in Vaccination 186 7.3.2 Lentiviral Vectors 187 7.
3.2.1 Advantages and Limitations of Lentiviral Vectors 188 7.3.2.2 Lentiviral Vectors Applications in Vaccination 189 7.3.3 Adeno-Associated Viral Vectors 190 7.
3.3.1 Advantages and Limitations of AAV 190 7.3.3.2 AAV Applications in Gene Therapy and Vaccination 191 7.3.4 Other DNA-Based Viral Vectors 193 7.
3.4.1 Baculoviral Vectors 193 7.3.4.2 Herpes Simplex Virus Vectors 193 7.3.4.
3 Poxviral Vectors 193 7.4 RNA-Based Viral Vectors 194 7.4.1 Retroviral Vectors 194 7.4.1.1 Advantages and Limitations 195 7.4.
2 Lentiviral Vectors 196 7.4.2.1 Advantages and Limitations 197 7.4.3 Alphaviral Vectors 201 7.4.3.
1 Advantages and Limitations 201 7.4.4 Other RNA-Based Viral Vectors 203 7.4.4.1 Sendai Virus Vectors 204 7.4.4.
2 Vesicular Stomatitis Virus Vectors 205 7.5 Vector Engineering and Modifications 205 7.5.1 Enhancing Vector Safety 206 7.5.2 Improving Vector Targeting and Tropism 207 7.5.3 Regulatory Considerations and Quality Control 207 7.
6 Preclinical and Clinical Applications 208 7.6.1 Gene Therapy Applications 209 7.6.1.1 Inherited Disorders 209 7.6.1.
2 Neurological Disorders 210 7.6.2 Vaccination Applications 210 7.6.2.1 Viral Vector-Based Vaccines 210 7.6.2.
2 Genetic Vaccines 212 7.7 Conclusion 212 References 213 8 Manufacturing and Control of Viral-Vector Vaccines: Challenges 221 Vivek P. Chavda, Dixa A. Vaghela, Dhunusmita Barman, Arzoo Newar and Ahmed Nasima 8.1 Introduction 222 8.2 Fundamentals of Viral-Vectored Vaccine Manufacturing 223 8.2.1 Viral Vector Construction 223 8.
2.2 Development of the Viral Vector in Bacteria Through Homologous Recombination 224 8.2.2.1 Production of the Viral Vector Using Cre/loxP Recombination System 224 8.2.3 Cell Line Development 224 8.2.
3.1 Designer Cell Lines and Cell Line Immortalization 225 8.2.3.2 Development of Stable Cell Lines for Vaccine Constitutive Expression 226 8.2.4 Upstream Processing 226 8.2.
4.1 Cultivation Process and Harvest Timing of the Virus 226 8.2.5 Downstream Processing 227 8.2.5.1 Purification of Viral Vectors 227 8.2.
5.2 Purification of a Large Stock of Viral Vector 227 8.2.5.3 Purification of Viral Vectors Using CsCl Density Gradient Centrifugation 228 8.2.5.4 Stable Liquid Virus Formulation Development 228 8.
3 Challenges in Manufacturing Viral-Vectored Vaccines 229 8.3.1 Scale-Up and Production Yield Challenges 229 8.3.2 Ensuring Genetic Stab.