Viral Vectors for Vaccine Delivery

Vivek P. Chavda is an assistant professor in the Department of Pharmaceutics and Pharmaceutical Technology, L.M. College of Pharmacy, India with over eight years of experience in biologic research. He has over 250 peer-reviewed national and international publications, including 38 book chapters, seven edited books, ten book chapters, seven patents, and numerous newsletter articles to his credit. His research interests include the development of biologics processes and formulations, medical device development, nano-diagnostics, non-carrier formulations, long-acting parenteral formulations, and nano-vaccines. Vasso Apostolopoulos, PhD, is the Vice-Chancellor’s Distinguished Fellow and Director of the Immunology and Translational Research Group at Victoria University and the Immunology Program Director at the Australian Institute for Musculoskeletal Science. She has over 510 research publications and 22 patents to her credit and has received over 100 awards for her research work. Her research interests include vaccine and drug development for cancer, chronic, infectious, and autoimmune diseases.

• Preface xv1 Introduction to Viral Vectors 1Anjali P. Bedse, Suchita P. Dhamane, Shilpa S. Raut, Komal P. Mahajan and Kajal P. Baviskar1.1 Introduction 21.2 Baculovirus Vectors 31.3 Adenovirus Vectors 41.4 Poxvirus Vectors 61.5 Herpes Virus Vectors 81.6 Epstein-Barr Virus Vectors 91.7 Retrovirus Vectors 101.8 Lentivirus Vectors 111.9 Adeno-Associated Virus (AAV) 131.10 Applications of Viral Vectors 141.10.1 Viral Vectors for Vaccine Development 141.10.2 Gene Therapy: The Performance of Viral Vectors 151.10.3 Clinical Trials 151.11 Safety Issues of Viral Vector/Biosafety Challenges 161.12 Conclusion 18References 192 Viral Vector Construction 25Suneetha Vuppu, Toshika Mishra, Shatakshi Mishra, Stany B. and Anushka Das2.1 Introduction 262.2 Applications of Viral Vector 272.3 Viral Vectors 292.3.1 Adenoviruses 292.3.2 Retroviruses 352.3.3 Lentiviruses 362.3.4 Poxviruses 362.3.5 Adeno-Associated Viruses 372.3.6 Herpes Simplex Viruses 382.3.7 Alphaviruses 392.3.8 Flaviviruses 392.3.9 Rhabdoviruses 402.3.10 Newcastle Disease Virus 402.3.11 Coxsackieviruses 412.3.12 Measles Virus 412.4 Construction of Viral Vectors 422.5 Challenges 462.5.1 Immune Response 462.5.2 Specificity of the Transgene Delivery 472.5.3 Insertional Mutagenesis 482.6 Advancements in Technology of Viral Vector Construction 492.7 Conclusion and Future Prospects 51Acknowledgments 53References 533 The Role of Adjuvants in the Application of Viral Vector Vaccines 65Vivek P. Chavda, Anjali P. Bedse and Shilpa S. Raut3.1 Introduction 663.2 Viral Vector Vaccines: A Powerful Platform 673.3 Challenges Associated with Viral Vector Vaccines 693.3.1 Preexisting Immunity against the Viral Vector 693.3.2 Safety Concerns Related to Insertional Mutagenesis 703.3.3 Scalability and Manufacturing Challenges 723.4 The Role of Adjuvants in Overcoming Challenges 723.4.1 Mechanisms of Action of Adjuvants 723.4.2 Innate Immune Stimulation 733.4.3 Adaptive Immune Response Enhancement 733.4.4 Different Classes of Adjuvants Used with Viral Vector Vaccines 743.4.4.1 Classes of Adjuvants 743.4.5 Targeting CLR Pathway 753.4.6 Saponins 753.4.7 Cytokines and Chemokines 763.4.8 Case Studies of Specific Adjuvants Used with Viral Vector Vaccines 763.5 Optimizing Adjuvant Design for Viral Vector Vaccines 763.5.1 Importance of Adjuvant Selection and Formulation 763.5.2 Adjuvant Formulation Development 773.5.3 Adjuvant Formulations for the Development of New Vaccines 773.5.4 Strategies for Optimizing Adjuvant Design 783.5.4.1 Dose Sparing 783.5.4.2 Enabling a More Rapid Immune Response 783.5.4.3 Antibody Response Broadening 783.5.4.4 Antibody Response Magnitude and Functionality 793.5.5 Delivery Systems 793.5.5.1 Targeting Specific Immune Cell Populations 793.5.5.2 Combination Adjuvants 793.5.5.3 Challenges and Future Directions in Adjuvant Development for Viral Vector Vaccines 803.6 Conclusion 80References 814 Replication-Competent Viral Vectors for Vaccine Delivery 91Vivek P. Chavda, Pankti C. Balar, Dixa A. Vaghela, Divya Teli, Amit Chaudhari and Shahnaz Alom4.1 Introduction 924.2 Types of Replication-Competent Viral Vectors 934.2.1 Adenoviruses (AdVs) 934.2.2 Vesicular Stomatitis Viruses (VSVs) 934.2.3 Modified Vaccinia Ankara (MVA) 944.2.4 Measles Virus (MV) 944.2.5 Influenza Virus (IV) 954.3 Mechanisms of RCVV-Mediated Vaccination 974.4 Applications of Replication-Competent Viral Vectors 1014.4.1 Prophylactic Vaccines 1014.4.2 Therapeutic Vaccines 1024.4.2.1 Vesicular Stomatitis Virus 1024.4.2.2 Cytomegalovirus 1034.4.2.3 Measles Virus 1044.4.2.4 Adenoviral Vectors 1044.4.2.5 Applications of Replication-Competent Viral Vectors against COVID- 19 1054.4.3 Cancer Immunotherapy 1114.5 Conclusion 115References 1165 Nonreplicating Viral Vectors for Vaccine Delivery 125Pankti C. Balar and Vivek P. Chavda5.1 Introduction 1265.2 Nonreplicating Viral Vectors: Types and Characteristics 1275.2.1 Adenoviral Vectors 1275.2.2 Non-Adenoviral Vectors 1285.2.3 Key Characteristics of Nonreplicating Vectors 1295.2.3.1 Immunogenicity 1295.2.3.2 Safety 1305.2.3.3 Stability 1315.2.3.4 Targeted Delivery 1315.3 Engineering Nonreplicating Viral Vectors for Vaccine Design 1325.3.1 Capsid Modification 1325.3.2 Promoter Engineering 1335.3.3 Transgene Optimization 1345.3.4 Immune Evasion Strategies 1345.4 Applications of Nonreplicating Viral Vectors in Vaccinology 1365.5 Optimizing Nonreplicating Viral Vectors for Vaccine Delivery 1385.5.1 Enhancing Transduction Efficiency 1385.5.2 Reducing Immunogenicity and Toxicity 1395.5.3 Improving Antigen Expression and Presentation 1395.5.4 Addressing Preexisting Immunity 1405.5.5 Targeting Vector Delivery to Secondary Lymphoid Organs 1415.6 Challenges and Future Perspectives 1415.7 Conclusion 143References 1446 Genetically Modified Viral Vectors for Vaccine Delivery 149Deepshi Arora, Yugam Taneja, Diksha Gulati, Manish Kumar, Anil Pareek and Rupesh K. Gautam6.1 Introduction 1506.2 Genetic Modification of Viral Vectors 1536.3 Applications of Genetically Modified Viral Vectors 1556.4 Administration of Vaccines 1596.5 Immune Response and Protection 1616.6 Case Studies 1636.7 Challenges and Future Directions 1656.8 Conclusion 168References 1717 DNA- and RNA-Based Viral Vectors 179Devesh U. Kapoor, Bhumi Bhatt, Dipansu Sahu, Rajiv R. Kakkar, Sonam M. Gandhi and Rupesh K. Gautam7.1 Introduction to Viral Vectors 1807.1.1 Definition and Overview 1807.1.2 Importance in Vaccine Delivery and Vaccination 1807.2 Basics of Deoxyribonucleic Acid (DNA) and Ribonucleic Acid (RNA) Viruses 1807.2.1 Structure and Replication of DNA Viruses 1817.2.2 Structure and Replication of RNA Viruses 1817.2.3 Characteristics Relevant to Vector Development 1827.2.3.1 Plasmids 1827.2.3.2 Viral Vectors 1837.2.3.3 Artificial Chromosomes 1837.3 DNA-Based Viral Vectors 1837.3.1 Adenoviral Vectors 1837.3.1.1 Advantages and Limitations of Adenoviral Vectors 1857.3.1.2 Adenoviral Vectors Applications in Vaccination 1867.3.2 Lentiviral Vectors 1877.3.2.1 Advantages and Limitations of Lentiviral Vectors 1887.3.2.2 Lentiviral Vectors Applications in Vaccination 1897.3.3 Adeno-Associated Viral Vectors 1907.3.3.1 Advantages and Limitations of AAV 1907.3.3.2 AAV Applications in Gene Therapy and Vaccination 1917.3.4 Other DNA-Based Viral Vectors 1937.3.4.1 Baculoviral Vectors 1937.3.4.2 Herpes Simplex Virus Vectors 1937.3.4.3 Poxviral Vectors 1937.4 RNA-Based Viral Vectors 1947.4.1 Retroviral Vectors 1947.4.1.1 Advantages and Limitations 1957.4.2 Lentiviral Vectors 1967.4.2.1 Advantages and Limitations 1977.4.3 Alphaviral Vectors 2017.4.3.1 Advantages and Limitations 2017.4.4 Other RNA-Based Viral Vectors 2037.4.4.1 Sendai Virus Vectors 2047.4.4.2 Vesicular Stomatitis Virus Vectors 2057.5 Vector Engineering and Modifications 2057.5.1 Enhancing Vector Safety 2067.5.2 Improving Vector Targeting and Tropism 2077.5.3 Regulatory Considerations and Quality Control 2077.6 Preclinical and Clinical Applications 2087.6.1 Gene Therapy Applications 2097.6.1.1 Inherited Disorders 2097.6.1.2 Neurological Disorders 2107.6.2 Vaccination Applications 2107.6.2.1 Viral Vector–Based Vaccines 2107.6.2.2 Genetic Vaccines 2127.7 Conclusion 212References 2138 Manufacturing and Control of Viral-Vector Vaccines: Challenges 221Vivek P. Chavda, Dixa A. Vaghela, Dhunusmita Barman, Arzoo Newar and Ahmed Nasima8.1 Introduction 2228.2 Fundamentals of Viral-Vectored Vaccine Manufacturing 2238.2.1 Viral Vector Construction 2238.2.2 Development of the Viral Vector in Bacteria Through Homologous Recombination 2248.2.2.1 Production of the Viral Vector Using Cre/loxP Recombination System 2248.2.3 Cell Line Development 2248.2.3.1 Designer Cell Lines and Cell Line Immortalization 2258.2.3.2 Development of Stable Cell Lines for Vaccine Constitutive Expression 2268.2.4 Upstream Processing 2268.2.4.1 Cultivation Process and Harvest Timing of the Virus 2268.2.5 Downstream Processing 2278.2.5.1 Purification of Viral Vectors 2278.2.5.2 Purification of a Large Stock of Viral Vector 2278.2.5.3 Purification of Viral Vectors Using CsCl Density Gradient Centrifugation 2288.2.5.4 Stable Liquid Virus Formulation Development 2288.3 Challenges in Manufacturing Viral-Vectored Vaccines 2298.3.1 Scale-Up and Production Yield Challenges 2298.3.2 Ensuring Genetic Stability and Vector Integrity 2308.3.3 Manufacturing Consideration for Different Vector Types 2348.4 Quality Control and Assurance in Vaccine Manufacturing 2358.4.1 Regulatory Requirements and Quality Standards 2368.4.2 Analytical Methods for Assessing Viral Vector Purity and Potency 2378.4.3 Process Validation and Quality Assurance Strategies 2388.4.3.1 Process Validation Using a Life Cycle Approach: From R&D to Clinical Trials to Commercial Scale Regulation 2398.4.3.2 Validation Strategy Based on Risk: Quality Risk Management System 2398.5 Technological Advances and Innovations in Manufacturing 2398.5.1 Novel Manufacturing Platforms and Technologies 2398.5.2 Automation and Process Optimization 2438.6 Supply Chain and Distribution Challenges 2448.7 Regulatory Hurdles and Compliances 2468.7.1 Regulatory Approval Challenges 2468.7.2 Compliances with Good Manufacturing Practices (gmp) 2468.7.3 Strategies for Navigating Regulatory Pathways 2478.8 Future Perspectives and Emerging Solutions 2488.9 Conclusion 248References 2499 Viral Vectors in Veterinary Vaccine Development 257Anup Kumar, Pooja Pandita, Harsh Modi, Shahnaz Alom and Vivek P. Chavda9.1 Introduction 2589.2 Basics of Viral Vectors 2599.2.1 Definition and Characteristics of Viral Vectors 2599.2.2 Types of Viral Vectors Used in Veterinary Vaccines 2609.2.3 Advantages and Limitations of Viral Vectors 2619.3 Genetic Engineering of Viral Vectors 2629.3.1 Design and Construction of Viral Vectors 2629.3.1.1 Gene Insertion Techniques 2629.3.1.2 Promoters and Enhancers 2629.3.2 Safety Measures and Biosafety Considerations 2639.3.3 Quality Control and Characterization 2639.4 Delivery System for Viral Vector Vaccines 2659.4.1 Application of Nanotechnology in Vaccine Delivery 2659.4.2 Targeted Delivery Approaches: Viral Vectors as Nanocarriers for Targeted Mucosal and Systemic Vaccine Delivery System 2679.4.3 Novel Delivery Platforms and Technologies 2689.4.3.1 Transdermal Vaccine Delivery System 2689.4.3.2 Microneedle Arrays Delivery System for Viral Vector Vaccine 2699.4.3.3 Viral Vector for DNA Vaccine Delivery 2709.4.3.4 Needle-Free Vaccination for Viral Vector Vaccine Delivery 2719.4.3.5 Combination Vaccine Regimen for Viral Vector Vaccine Delivery 2729.5 Routes of Administration for Viral Vector Vaccines 2729.5.1 Parenteral Route of Administration 2739.5.1.1 Intravenous Route 2739.5.1.2 Intramuscular Route 2739.5.1.3 Subcutaneous Route 2749.5.1.4 Intradermal Route 2749.5.2 Mucosal Route of Administration 2749.5.2.1 Intranasal Route 2759.5.2.2 Oral Route 2769.6 Comparative Analysis of Different Administration Routes 2769.6.1 Parenteral Vaccine Delivery System 2769.6.2 Mucosal Vaccine Delivery System 2779.6.3 Challenges of the Mucosal Delivery System 2789.6.3.1 Advantages of the Oral Route 2789.6.3.2 Challenges of Oral Route 2799.6.3.3 Advantages of Intranasal Route 2799.6.3.4 Challenges of Intranasal Route 2799.7 Applications of Viral Vectors in Veterinary Vaccine Development 2809.7.1 Live Attenuated Viral Vector Vaccines 2809.7.2 Inactivated Viral Vector Vaccines 2809.7.3 DNA-Based Viral Vector Vaccines 2819.7.4 Subunit Viral Vector Vaccines 2819.7.5 Recombinant Viral Vector Vaccines 2829.7.6 Examples of Veterinary Vaccines Using Viral Vectors 2829.8 Immunology and Immune Response 2859.8.1 Mechanisms of Immune Response to Viral Vector Vaccines 2859.8.2 Adjuvants and Immune Enhancement 2869.8.3 Immune Memory and Longevity 2879.9 Safety and Regulatory Considerations 2919.9.1 Safety Assessment and Preclinical Studies 2919.9.2 Regulatory Approval Process for Veterinary Viral Vector Vaccines 2929.9.3 Post-Market Surveillance and Monitoring 2939.10 Notable Examples of Viral Vector Vaccines in Veterinary Medicine and Their Impact on Animal Health and Agriculture 2959.11 Challenges and Future Directions 2979.12 Conclusion 299References 30010 Advantages and Challenges of Viral Vector Vaccines 317Shilpa Dawre, Mahendra Prajapati and Ganesh Shevalkar10.1 Introduction 31710.2 Types of Viral Vectors for Vaccine Development 31910.2.1 Poxviruses Vectors 31910.2.2 Adenovirus Vectors 32210.2.3 Retrovirus Vectors 32210.2.4 Lentivirus Vectors 32310.2.5 Cytomegalovirus Vectors 32310.2.6 Sendai Virus Vectors 32310.2.7 Adeno-Associated Virus Vectors 32410.3 Mechanism of Action of Viral Vectors 32410.3.1 Self-Adjuvanting Nature of Viral Vector Vaccines 32510.3.2 Enhanced Cytotoxic CD8 + T Lymphocyte Production 32610.3.3 Conformational Antigen Expression on Host Cell Membranes Infected by a Vector 32710.3.4 Sustained Supply of Significant Amounts of Antigen 32710.4 Advantages of Viral Vector Vaccines 32710.4.1 Safety 32810.4.2 Stability 32810.4.3 Immunogenicity 32810.4.3.1 Humoral Immunity 32910.4.3.2 Cell-Mediated Immunity 32910.4.3.3 Mucosal Immunity 33010.5 Challenges of Viral Vector Vaccine 33110.5.1 Development of Immunity Against Viral Vectors 33110.5.2 Adverse Events 33110.5.3 Scale-Up Hurdles in Viral Vector Production 33210.5.3.1 Complexity and Variability of the Process 33210.5.3.2 Low Yield and High Cost 33310.5.3.3 Regulatory and Quality Control Challenges 33310.5.3.4 Restrictions of Frequent Culture Systems 33410.5.3.5 Formulation and Storage of Viral Vector Products 33410.5.3.6 Requirement of High-Cost Technologies 33510.5.3.7 Handling and Shipment 33510.6 Conclusion 336References 33611 Commercially Available Viral Vectors and Vaccines 341Vasso Apostolopoulos, Pankti C. Balar, Arun Kumar Singh and Vivek P. Chavda11.1 Introduction 34211.2 Viral Vector–Based Vaccines, Licensed for Humans 34211.2.1 Adenovirus Vector Vaccines 34211.2.2 Vesicular Stomatitis Virus Vector Vaccines 34611.2.3 Flavivirus Vector Vaccines 34711.2.4 Combination Virus Vectors: Ad5/Ad 26 34811.2.5 Combination Virus Vectors: Ad5/VSV 34811.2.6 Measles Virus Vector Vaccines 34911.2.7 Poxvirus Vector Vaccines 34911.3 Conclusion 350References 35012 Emerging Viral-Vector Technologies: Future Potential 357Vasso Apostolopoulos, Pankti C. Balar and Vivek P. Chavda12.1 Introduction 35812.2 New Emerging Viral Vectors for Vaccines 35812.3 Viral Vector Vaccines: What is Good and What is Not So Good 36012.4 Conclusion 361References 361Index 365