Viral Vectors for Vaccine Delivery E-Book
168,99 €
Mehr erfahren.
- Herausgeber: John Wiley & Sons
- Kategorie: Fachliteratur
- Sprache: Englisch
The book is essential for anyone interested in vaccine development, as it highlights the unique advantages of viral vector vaccines in triggering robust, long-lasting immunity and provides an in-depth exploration of the technology and advancements shaping the future of healthcare.
Viral vector vaccines have several unique advantages when compared to other vaccine platforms. These powerful vaccines are capable of triggering long-lasting cellular responses, such as cytotoxic T-lymphocytes, that eradicate virus-infected cells. Viral vector-based vaccines use a harmless virus to smuggle the instructions for making antigens from the disease-causing virus into cells, triggering protective immunity against them. In contrast to conventional antigen-containing vaccines, these vaccines use the body’s natural defense system to produce antigens by using a modified virus to deliver genetic code for an antigen. Viral Vectors for Vaccine Delivery provides a comprehensive overview of viral vectors and their applications in vaccine delivery. Its chapters explore various aspects of viral vector technology, from the basic principles of viral vector construction to the latest advancements in gene editing and manufacturing.
Readers will find that the book
- Offers a deep dive into the world of viral vectors, covering their principles, applications, and potential impact on healthcare;
- Explores how viral vectors are revolutionizing vaccine development, providing a more effective and targeted approach to disease prevention;
- Discusses the potential of viral vectors to address emerging health challenges and contribute to a healthier world.
Audience
Research scholars, pharma-process engineers, research scientists, pharmacy students and professionals from the pharmaceutical and biopharmaceutical industry interested in drug discovery, chemical biology, computational chemistry, medicinal chemistry, and bioinformatics
Sie lesen das E-Book in den Legimi-Apps auf:
Seitenzahl: 620
Veröffentlichungsjahr: 2025
Ähnliche
Table of Contents
Cover
Table of Contents
Series Page
Title Page
Copyright Page
Preface
1 Introduction to Viral Vectors
1.1 Introduction
1.2 Baculovirus Vectors
1.3 Adenovirus Vectors
1.4 Poxvirus Vectors
1.5 Herpes Virus Vectors
1.6 Epstein-Barr Virus Vectors
1.7 Retrovirus Vectors
1.8 Lentivirus Vectors
1.9 Adeno-Associated Virus (AAV)
1.10 Applications of Viral Vectors
1.11 Safety Issues of Viral Vector/Biosafety Challenges
1.12 Conclusion
References
2 Viral Vector Construction
2.1 Introduction
2.2 Applications of Viral Vector
2.3 Viral Vectors
2.4 Construction of Viral Vectors
2.5 Challenges
2.6 Advancements in Technology of Viral Vector Construction
2.7 Conclusion and Future Prospects
Acknowledgments
References
3 The Role of Adjuvants in the Application of Viral Vector Vaccines
3.1 Introduction
3.2 Viral Vector Vaccines: A Powerful Platform
3.3 Challenges Associated with Viral Vector Vaccines
3.4 The Role of Adjuvants in Overcoming Challenges
3.5 Optimizing Adjuvant Design for Viral Vector Vaccines
3.6 Conclusion
References
4 Replication-Competent Viral Vectors for Vaccine Delivery
4.1 Introduction
4.2 Types of Replication-Competent Viral Vectors
4.3 Mechanisms of RCVV-Mediated Vaccination
4.4 Applications of Replication-Competent Viral Vectors
4.5 Conclusion
References
5 Nonreplicating Viral Vectors for Vaccine Delivery
5.1 Introduction
5.2 Nonreplicating Viral Vectors: Types and Characteristics
5.3 Engineering Nonreplicating Viral Vectors for Vaccine Design
5.4 Applications of Nonreplicating Viral Vectors in Vaccinology
5.5 Optimizing Nonreplicating Viral Vectors for Vaccine Delivery
5.6 Challenges and Future Perspectives
5.7 Conclusion
References
6 Genetically Modified Viral Vectors for Vaccine Delivery
6.1 Introduction
6.2 Genetic Modification of Viral Vectors
6.3 Applications of Genetically Modified Viral Vectors
6.4 Administration of Vaccines
6.5 Immune Response and Protection
6.6 Case Studies
6.7 Challenges and Future Directions
6.8 Conclusion
References
7 DNA- and RNA-Based Viral Vectors
7.1 Introduction to Viral Vectors
7.2 Basics of Deoxyribonucleic Acid (DNA) and Ribonucleic Acid (RNA) Viruses
7.3 DNA-Based Viral Vectors
7.4 RNA-Based Viral Vectors
7.5 Vector Engineering and Modifications
7.6 Preclinical and Clinical Applications
7.7 Conclusion
References
8 Manufacturing and Control of Viral-Vector Vaccines: Challenges
8.1 Introduction
8.2 Fundamentals of Viral-Vectored Vaccine Manufacturing
8.3 Challenges in Manufacturing Viral-Vectored Vaccines
8.4 Quality Control and Assurance in Vaccine Manufacturing
8.5 Technological Advances and Innovations in Manufacturing
8.6 Supply Chain and Distribution Challenges
8.7 Regulatory Hurdles and Compliances
8.8 Future Perspectives and Emerging Solutions
8.9 Conclusion
References
9 Viral Vectors in Veterinary Vaccine Development
9.1 Introduction
9.2 Basics of Viral Vectors
9.3 Genetic Engineering of Viral Vectors
9.4 Delivery System for Viral Vector Vaccines
9.5 Routes of Administration for Viral Vector Vaccines
9.6 Comparative Analysis of Different Administration Routes
9.7 Applications of Viral Vectors in Veterinary Vaccine Development
9.8 Immunology and Immune Response
9.9 Safety and Regulatory Considerations
9.10 Notable Examples of Viral Vector Vaccines in Veterinary Medicine and Their Impact on Animal Health and Agriculture
9.11 Challenges and Future Directions
9.12 Conclusion
References
10 Advantages and Challenges of Viral Vector Vaccines
10.1 Introduction
10.2 Types of Viral Vectors for Vaccine Development
10.3 Mechanism of Action of Viral Vectors
10.4 Advantages of Viral Vector Vaccines
10.5 Challenges of Viral Vector Vaccine
10.6 Conclusion
References
11 Commercially Available Viral Vectors and Vaccines
11.1 Introduction
11.2 Viral Vector–Based Vaccines, Licensed for Humans
11.3 Conclusion
References
12 Emerging Viral-Vector Technologies: Future Potential
12.1 Introduction
12.2 New Emerging Viral Vectors for Vaccines
12.3 Viral Vector Vaccines: What is Good and What is Not So Good
12.4 Conclusion
References
Index
End User License Agreement
List of Tables
Chapter 1
Table 1.1
Viral vectors under clinical trial.
Chapter 2
Table 2.1
Applications of viral vectors in various biological fields.
Chapter 4
Table 4.1
Overview of replication-competent viral vector.
Table 4.2
Specifics of COVID-19 vaccine candidates based on viral vectors: Fin...
Table 4.3
Viral vaccine vectors candidates for cancer immunotherapy: Finished ...
Chapter 6
Table 6.1
Summary of different types of viral vectors along with their descrip...
Table 6.2
Comparison of genetically modified viral vector vaccines.
Chapter 7
Table 7.1
Different applications of lentiviral vectors in gene therapy.
Table 7.2
Numerous advantages of alpha viral vectors.
Table 7.3
Applications of vaccination.
Chapter 8
Table 8.1
Comparison of viral vectors.
Chapter 9
Table 9.1
Various viral vector types and their benefits and drawbacks.
Table 9.2
Considerations in viral vector design and construction.
Table 9.3
Main features and examples of veterinary vaccines using viral vector...
Table 9.4
The main features and examples of adjuvants for viral vector vaccine...
Table 9.5
The main features and examples of immune memory and longevity of vir...
Table 9.6
Key elements and procedures of the preclinical research and safety e...
Table 9.7
Essential actions and specifications of the regulatory approval proc...
Table 9.8
The key elements and procedures of the post-market surveillance and ...
Table 9.9
Notable examples of viral vector vaccines in veterinary medicine and...
Table 9.10
Current challenges in viral vector vaccine development.
Table 9.11
Research directions and innovations.
Table 9.12
Potential for cross-species vaccines.
Chapter 10
Table 10.1
List of clinical trials using viral vectors for vaccine development...
List of Illustrations
Chapter 1
Figure 1.1 Structure and types of herpesviruses.
Figure 1.2 Large-scale production of vector viruses using helper viruses.
Figure 1.3 HIV genome and lentiviral vector.
Figure 1.4 Lentiviral vector in gene therapy.
Chapter 2
Figure 2.1 Transfection by viral vectors (created by Vuppu
et al.
using Bioren...
Chapter 3
Figure 3.1 Activation of innate and adaptive immune responses in response to a...
Chapter 4
Figure 4.1 Mechanisms of antigen presentation following intramuscular vaccinat...
Chapter 6
Figure 6.1 Delivery of inserted gene into the host cell.
Chapter 7
Figure 7.1 Vector development characteristics.
Figure 7.2 DNA-based viral vectors.
Figure 7.3 Application of lentiviral vector in vaccination.
Chapter 8
Figure 8.1 Fundamentals of viral-vectored vaccine manufacturing and distributi...
Figure 8.2 The four main phases of the analytical tool development process.
Figure 8.3 An overview of different vaccine platform.
Chapter 10
Figure 10.1 Advantages and challenges of viral vector vaccines.
Chapter 11
Figure 11.1 Schematic diagram of recombinant viral vectors and vaccines used i...
Chapter 12
Figure 12.1 Schematic diagram of viral vectors used in vaccines in humans and ...
Guide
Cover Page
Table of Contents
Series Page
Title Page
Copyright Page
Preface
Begin Reading
WILEY END USER LICENSE AGREEMENT
Pages
ii
iii
iv
xv
xvi
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
Scrivener Publishing100 Cummings Center, Suite 541JBeverly, MA 01915-6106
Publishers at ScrivenerMartin Scrivener ([email protected])Phillip Carmical ([email protected])
Viral Vectors for Vaccine Delivery
Edited by
Vivek P. Chavda
Dept. of Pharmaceutics and Pharmaceutical Technology, L. M. College of Pharmacy, Ahmedabad, Gujarat, India
and
Vasso Apostolopoulos
School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria, Australia
This edition first published 2025 by John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA and Scrivener Publishing LLC, 100 Cummings Center, Suite 541J, Beverly, MA 01915, USA© 2025 Scrivener Publishing LLCFor more information about Scrivener publications please visit www.scrivenerpublishing.com.
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions.
Wiley Global Headquarters111 River Street, Hoboken, NJ 07030, USA
For details of our global editorial offices, customer services, and more information about Wiley products visit us at www.wiley.com.
Limit of Liability/Disclaimer of WarrantyWhile the publisher and authors have used their best efforts in preparing this work, they make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives, written sales materials, or promotional statements for this work. The fact that an organization, website, or product is referred to in this work as a citation and/or potential source of further information does not mean that the publisher and authors endorse the information or services the organization, website, or product may provide or recommendations it may make. This work is sold with the understanding that the publisher is not engaged in rendering professional services. The advice and strategies contained herein may not be suitable for your situation. You should consult with a specialist where appropriate. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages. Further, readers should be aware that websites listed in this work may have changed or disappeared between when this work was written and when it is read.
Library of Congress Cataloging-in-Publication Data
ISBN 978-1-394-27153-5
Front cover image courtesy of Adobe FireflyCover design by Russell Richardson
Preface
The development of vaccines has been a cornerstone of public health, preventing countless diseases and saving millions of lives. However, traditional vaccine approaches often face limitations, such as the need for multiple doses, the potential for adverse reactions, and the inability to induce long-lasting immunity against complex pathogens. In recent decades, viral vectors have emerged as a promising alternative, revolutionizing the field of vaccine development.
This book provides a comprehensive overview of viral vectors and their applications in vaccine delivery. Its chapters explore various aspects of viral vector technology, from the basic principles of viral vector construction to the latest advancements in gene editing and manufacturing.
To begin, the book introduces the concept of viral vectors and their advantages over traditional vaccine platforms. Subsequent chapters delve into the intricacies of viral vector construction, including the selection of appropriate viral backbones, the insertion of foreign genes, and the optimization of vector design for maximum immunogenicity. The role of adjuvants in enhancing the efficacy of viral vector vaccines is also discussed, highlighting their importance in boosting immune responses and improving vaccine potency.
The next section explores the different types of viral vectors used for vaccine delivery, including replication-competent and non-replicating vectors. Replication-competent vectors mimic natural infections, inducing a robust immune response, while non-replicating vectors are safer but may require multiple doses. Genetically modified viral vectors, such as those engineered for targeted delivery or enhanced antigen presentation, are also covered.
The book further delves into the specific applications of viral vectors in vaccine development, including their use in veterinary medicine and the development of vaccines against emerging infectious diseases. The advantages and challenges associated with viral vector vaccines are discussed, along with the commercially available viral vector vaccines and the future potential of this technology.
This book serves as a valuable resource for researchers, scientists, and healthcare professionals working in the field of vaccine development. It provides a comprehensive understanding of viral vector technology and its potential to address the challenges of vaccine design and delivery. By exploring the latest advancements and future prospects, this book aims to contribute to the development of safer, more effective, and more accessible vaccines for a healthier global population. The editors are grateful to everyone who has supported their work and also wish to thank Martin Scrivener and Scrivener Publishing for their support and publication.
Editors
Vivek P. ChavdaVasso Apostolopoulos
1Introduction to Viral Vectors
Anjali P. Bedse1*, Suchita P. Dhamane2, Shilpa S. Raut1, Komal P. Mahajan3 and Kajal P. Baviskar4
1Department of Pharmaceutics, K K Wagh College of Pharmacy, Nashik, Maharashtra, India
2Department of Pharmaceutics, JSPM’s Jayawantrao Sawant College of Pharmacy & Research, Hadapsar, Pune, Maharashtra, India
3Department of Pharmacology, K K Wagh College of Pharmacy, Nashik, Maharashtra, India
4Department of Pharmaceutical Chemistry, K K Wagh College of Pharmacy, Nashik, Maharashtra, India
Abstract
Viral vector manipulation is the most effective way to transfer genes to modify a specific cell type or tissue. Therapeutic genes can also be expressed through this technique. Many virus species are currently being studied for their ability to introduce genes into cells for transgenic expression, which can be either temporary or permanent. These comprise herpes simplex viruses, baculoviruses, adeno-associated viruses, poxviruses, γ-retroviruses, lentiviruses, and adenoviruses (Ads). The selection of a virus for regular clinical usage depends upon several factors, including transgenic expression effectiveness, production ease, safety, toxicity, and stability. An introduction to the general properties of viral vectors frequently used in gene transfer, as well as their benefits and drawbacks for gene therapy applications, is given in this chapter.
Keywords: Viral vectors, gene transfer, transgene expression, adenoviruses, gene therapy
1.1 Introduction
For decades, traditional vaccination platforms such as live-attenuated or killed viral vaccines have been utilized effectively in inducing long-term immunity to various kinds of pathogenic human diseases. However, for many human infections, such vaccination platforms, especially liveattenuated vaccines, are unsuitable for human usage due to safety issues, low efficacy, or basic impracticality [1].
In a phase 1 clinical trial of a live-attenuated dengue virus vaccine, side effects produced by the vaccine virus strain’s under-attenuation were observed [2].
Certain infections, including the Ebola and Marburg viruses belonging to the Filoviridae family, are so deadly that live-attenuated vaccines are not even considered because the risk of the vaccine strain becoming under-attenuated or reverting to a pathogenic state would be too great. The persistent need for developing novel, safer, and more effective vaccine platforms has led researchers to explore alternate approaches for vaccine production, including DNA vaccines, viral-vectored immunizations, and recombinant protein subunit vaccines. One of the most promising platforms for recombinant vaccine research is the viral vector. A viral vector is comparable to a small delivery device that can transport genetic material to the cell nucleus. The viral vector has the genetic material loaded and packaged into it. The purpose of using viral vectors for vaccination is to introduce the target pathogen’s naturally existing antigens to the immune system without the infectious pathogen [1].
Viral vectors can be categorized into two main groups based on their genomic behavior within host cells: those that integrate into the host cellular chromatin, such as oncoretroviruses and lentiviruses, and those that primarily exist as extrachromosomal episomes within the cell nucleus, including adeno-associated viruses (AAV), adenoviruses (Ads), and herpesviruses. This classification is crucial for understanding their mechanisms of action and potential applications in gene therapy and vaccination. The selection of viral vectors for clinical use is influenced by several critical factors, including stability, toxicity, safety, ease of manufacturing, and the efficiency of transgene expression. These considerations ensure that the chosen vector is suitable for the intended therapeutic application while minimizing risks to the patient. Viral vectors encompass both RNA and DNA viruses, which can be further divided based on their genomic structure into single-stranded (ss) and double-stranded (ds) genomes. For instance, retroviruses typically possess an ssRNA genome that must be reverse-transcribed into dsDNA before integration into the host genome. In contrast, Ads are characterized by their dsDNA genomes and are known for their ability to transiently express genes without integrating into the host genome.
The distinct properties of each viral vector type contribute to their effectiveness in various therapeutic contexts. For example, retroviral vectors are particularly effective for stable gene integration in dividing cells, while AAVs are favored for their low immunogenicity and ability to transduce both dividing and nondividing cells. Ads offer high transduction efficiency and large packaging capacity, making them suitable for delivering larger genetic payloads [3, 4].
1.2 Baculovirus Vectors
A safe, nontoxic, non-integrative vector with a high replication capability is the baculovirus. Since baculoviruses may infect both latent and growing cells, they are also a highly versatile, inexpensive vector with a wide tissue and host tropism. Additionally, they are more biosafe since they only reproduce in insect cells—not in mammalian cells. Baculoviruses are a desirable choice for gene transfer due to their advantageous characteristics. Regenerative medicine, anticancer treatments, and vaccine development have all benefited greatly from the substantial advancements made in using baculoviruses in gene therapy. Nowadays, the main applications of baculoviruses are in the manufacture of vaccines and recombinant proteins. New avenues for the production of vaccines of the next generation have been made possible by the stimulation of mucosal and systemic immune responses by baculoviruses through oral or intranasal delivery. This human-friendly virus will undoubtedly be promoted as a viable vector for clinical applications if further knowledge about the biology of baculoviruses and their interactions with non-native hosts is obtained [5, 6].
The term “baculovirus” refers to the unique rod-shaped viral particles produced in infected insect cells, known as occlusion bodies. Baculoviruses are frequently employed in insect cell culture systems as expression vectors. The baculovirus can be modified to include foreign genes in its genome, which allows the virus to infect insect cells. This makes it possible to produce significant quantities of recombinant proteins for scientific or commercial uses.
Baculoviruses have been assessed as potential carriers of antigens to elicit immunological responses, making them attractive candidates for the production of vaccines [5].
1.3 Adenovirus Vectors
Adenoviral vectors (AdVs) have emerged as the most widely used vehicle for gene therapy in cancer treatment. These vectors are also employed in vaccination strategies to deliver foreign antigens and in various gene therapy applications. In many cases, AdVs are engineered to be replicationdefective; this involves the deletion of essential viral genes, which are then replaced with a genetic cassette that expresses a therapeutic gene. Such modifications allow for targeted gene delivery while minimizing the risk of viral replication in healthy tissues. In the context of cancer therapy, replicationcompetent AdVs, known as oncolytic vectors, have been developed. These vectors are specifically designed to replicate within cancer cells, utilizing the natural lytic cycle of the virus to induce cell death selectively. By exploiting the unique vulnerabilities of tumor cells, oncolytic Ads can effectively target and destroy malignant tissues while sparing normal cells.
Numerous clinical trials have demonstrated the safety and therapeutic efficacy of both replication-defective and replication-competent AdVs. For instance, studies have shown that these vectors can elicit robust immune responses against tumors, enhancing their potential as therapeutic agents. The ability of AdVs to infect a broad range of cell types and their capacity to induce strong cellular and humoral immune responses further support their utility in cancer treatment. Moreover, AdVs can be engineered to express immune-modulatory molecules or tumor-specific antigens, which can enhance antitumor immunity. This versatility makes them suitable not only for direct cancer therapies but also for combination strategies with existing treatments such as immune checkpoint inhibitors [7].
Although Ads have been used as gene delivery vehicles since the invention of gene therapy, Ad vaccines, like mRNA vaccines, are a more recent approach [8, 9]. The viral replication genes E1 and/or E3 are removed and substituted for the desired transgene, like an antigen, to form a vector. This prevents the virus from expressing the desired antigen and stops it from replicating its genome after infection. In comparison to mRNA vaccines, Ads have a number of advantages, such as the previously mentioned low cost and thermostability [10].
Ad vector vaccinations generally elicit robust transgenic antigen-specific cellular (specifically, CD8+ T cells) and/or humoral immune responses, making them immunogenic vaccines [11].
The potential of AdVs to elicit a potent and well-balanced immune response makes them ideal for use in the COVID-19 pandemic. These vectors have been studied as vaccine agents for a variety of infectious diseases [12, 13]. Early AdV systems faced biological challenges, but the distinct molecular characteristics of these vectors facilitated the rapid development of vaccines with complex designs [10, 14].
AdVs have the benefit of high infection effectiveness and a significant cargo limit. AdVs have a significant disadvantage in that they are highly cytotoxic; nevertheless, this characteristic can be useful when the vectors are employed as oncolytic viruses. Although there are drawbacks of transient gene expression, safety benefits outweigh them as gene expression on unintentional targets would be transient [14].
AdVs are categorized into first, second, and third generations based on their genetic makeup. First-generation AdVs can only be produced using a packaging cell line that expresses the E1 protein; they are not capable of self-replication. The most widely utilized packaging cells are human embryonic kidney 293 cells.
Most human cells produce E1A-like proteins; therefore, even firstgeneration AdVs with deleted E1 sections can cause robust host immune responses and persistent cytotoxicity in transduced host cells. Another strategy was to develop a second-generation Ad without E2 and E4 deletions in order to lessen the host cell’s immune response to the vector. The E2 section encodes genes related to Ad replication, while the E4 region encodes regulatory proteins related to DNA transcription.
Second-generation Ads continue to elicit host immune responses and reduce transgenic expression in target cells by expressing adenoviral proteins through the remaining genes. The production of third-generation AdVs, often referred to as “helper-dependent vectors,” involves cointroducing a “helper adenovirus”—a virus that carries the genes required for replication—into the packed cells. Third-generation Ads can be contaminated by helper Ads, and self-propagating Ads can result from homologous recombination between helper viruses and packing cells [15].
Gendicine, a recombinant human p53 adenovirus, was approved by the China Food and Drug Administration (CFDA) in 2003 as a first-in-class gene therapy product for head and neck cancer treatment. Gendicine is a biological medication that can be given in three different ways: intravascular infusion, intracavity, or minimally invasive intratumoral injection. The wild-type (wt) p53 protein produced by Gendicine-transduced cells has a tumor-suppressive role in response to cellular stress. It induces apoptosis, senescence, and/or autophagy, depending on the conditions of the cellular stress. It also promotes cell-cycle arrest and DNA repair. Gentacine has demonstrated notably higher response rates when combined with radiation and chemotherapy than when used with traditional therapies alone. Additionally, its safety record is really good. Apart from head and neck cancer, other cancer types and illness stages have also been effectively treated with metronidazole. No major side effects have been noted, with the exception of 50 to 60% of patients experiencing vector-associated transient fever, which persisted for a few hours [16].
1.4 Poxvirus Vectors
Poxviruses are a large, complex virus belonging to the Poxviridae family that can affect both vertebrates and invertebrates. Poxviruses are comparatively large and oval-shaped viruses. Poxviridae is subdivided into two subfamilies: Chordopoxvirinae (vertebrate poxviruses) and Entomopoxvirinae (insect poxviruses). The subfamily Chordopoxvirinae has been further divided into nine genera, four of which contain viruses that cause diseases in humans (Orthopoxvirus, Parapoxvirus, Molluscipoxvirus, and Yatapoxvirus). Smallpox and molluscum contagiosum are diseases that affect humans, whereas the other two are zoonotic infections. The virion is enclosed, and the genome is protected in a protein sheath. Among all DNA viruses, poxviruses are distinct in that they can only reproduce outside of the nucleus, in the cytoplasm of the host cell. To encode the various enzymes and proteins involved in viral DNA replication and gene transcription, a large genome is therefore required [17].
Poxvirus infections can cause lesions, skin nodules, or a severe rash. Variola virus, the causative agent of smallpox, caused enormous morbidity and mortality in human communities before its effective eradication. The smallpox vaccine, which was essential in the eradication of smallpox, is based on the vaccinia virus (VV), a poxvirus closely related to the variola virus. The vaccination protected against smallpox without developing it. Though smallpox is no longer around, other poxviruses can infect humans. Monkeypox and VVs are two examples. Monkeypox is related to smallpox but produces a less severe sickness in humans. The smallpox vaccine is based on the VV.
Poxviruses have been utilized as vectors for foreign gene expression in mammalian cells. Modified poxviruses, such as modified vaccinia Ankara (MVA), are used as vaccine vectors in the treatment of a variety of infectious diseases. Poxviruses are open to genetic modification because of their enormous genomes. This has been used for various applications, including gene delivery vector application in research and the development of recombinant vaccines [18].
The ability of poxviruses to produce cellular and humoral immunity, their huge genome size with several immunomodulatory genes, and their tolerance for significant heterologous gene insertions are the major characteristics that make them good antigen delivery platforms and vaccine vectors. Initially, the VV was designed to express heterologous genes. Later, with promising results, the potential of using swinepox, parapoxvirus, and avipoxvirus as vectors was additionally examined. In order to mitigate the safety risks associated with wt poxviruses, a variety of severely attenuated strains with replication defects have been created, primarily by repetitive cycles in cell culture [19].
The thymidine kinase (TK) gene has been specifically targeted for insertional inactivation in the majority of recombinant poxviruses produced too far. This involves introducing a heterologous gene into the TK locus within the poxvirus genome. Poxviridae family recombinant VV vectors proliferate and transcribe their genome in infected cells’ cytosol. Thus, it is important that viral DNA is incorporated into the host’s genome. VV is the preferred vector for transient gene expression since it infects almost all types of mammalian cells. Its massive, adaptable genome makes it possible to insert large DNA segments up to 25 kb in size. This virus has three distinct stages in its infectious cycle. Genes in the early phase code for enzyme proteins, while genes in the intermediate phase control the expression of genes in the late phase, which codes for structural proteins. Promoting the expression of the inserted gene of interest is possible by means of the 7.5kDa protein that encodes the promoter gene, which is active during both the early and late phases of infection. The wt VV is cytolytic, while less virulent poxvirus vectors like MVA or fowl pox virus are commonly used for cell transduction.
To create safer and more versatile poxvirus-vectored vaccine candidates, other immunomodulatory genes have also been used recently. In heterologous prime-boost vaccination regimens, in which poxvirus vectors are combined with other killed or DNA vaccine formulations, it has been demonstrated that poxvirus vectors are highly effective. The number of vaccinations based on the poxvirus has been approved for use against various animal infections, such as the canine distemper virus (CDV), rabies virus (RabV), avian influenza virus (AIV), and West Nile virus (WNV) [19].
VV is a member of the poxvirus family. An icosahedral papovavirus is called Simian virus-40(SV40). Recently, alterations have been implemented in Simian virus-40 (SV40) to enable it to serve as a vector for gene delivery. Gene transfer vectors that exhibit certain distinctive characteristics include recombinant SV40 (rSV40) vectors: SV40 is a widely recognized virus, and it is simple to create nonreplicative vectors at titers of 1012 IU/ml. Additionally, these successfully transduce both dormant and proliferating cells, are nonimmunogenic, and provide a broad variety of cell types with sustained transgene expression. The limited ability to clone viruses and the potential risks associated with the random integration of the viral genome into the host genome are currently the drawbacks of using rSV40 vectors for gene therapy [20].
1.5 Herpes Virus Vectors
Herpesviruses are well known for being able to cause latent infections. Some cells may experience the virus going dormant after an initial active infection, and subsequent reactivations can result in recurring infections. Many individuals carry herpes viruses without showing any symptoms, and these kinds of viruses are very widespread. Some people, particularly those with compromised immune systems, may experience more severe herpesvirus infections and consequent complications [21].
Alphaherpesvirinae, Betaherpesvirinae, and Gammaherpesvirinae are the three subfamilies of the nine herpes viruses that are known to infect humans (Figure 1.1).
Herpesviruses with reduced virulence are engineered to carry heterologous immunogens that specifically target a number of hazardous and important infections. These compounds are remarkable for their ability to elicit humoral and cell-mediated immune responses, as well as to accept large amounts of foreign DNA.
Figure 1.1 Structure and types of herpesviruses.
A strong basis for the advancement of herpesvirus-based vectors is established by a better understanding of the interaction between the vector and the host. Currently, a variety of molecular techniques, including codon optimization, homologous and two-step en passant mutagenesis, BAC technology, and the CRISPR/Cas9 system, are used to facilitate the generation of herpesvirus-based recombinant vaccine vectors [22].
Herpes simplex virus (HSV) vectors are appropriate for transferring and expressing several large therapeutic genes in brain neurons over an extended period of time, even in the total absence of viral gene expression. The advanced vector technologies are safe, long-lasting, and noninflammatory within the nucleus of nerve cells. HSV may eventually be utilized to treat a number of neurodegenerative disorders with an identified inherited cause [21].
1.6 Epstein-Barr Virus Vectors
The Epstein-Barr virus (EBV) vector is characterized by its ability to persist in the host cell nucleus as an episome, rather than integrating into the host genome. This property renders it a highly accessible and efficient vector for use in human cell lines. The EBV vector comprises two key DNA components: the nuclear antigen-1 (EBNA1) gene, which is expressed by the virus, and the OriP sequence, which serves as the origin of plasmid replication. The EBNA1 protein plays a crucial role in maintaining the stability of the episome by binding to the OriP sequence. This interaction facilitates the anchoring of OriP-containing plasmids to nuclear proteins within the host cell, allowing them to remain stable episomes during cell division. As a result, these plasmids can replicate alongside the host’s cellular machinery without disrupting genomic integrity. The unique characteristics of EBV vectors make them particularly suitable for various applications in gene therapy and vaccine development. Their episomal nature allows for sustained expression of therapeutic genes without the risks associated with genomic integration, such as insertional mutagenesis. This aspect is especially important in therapeutic contexts where long-term gene expression is desired. Furthermore, EBV vectors can be engineered to enhance their functionality. For instance, modifications can be made to improve their replication efficiency or to include additional regulatory elements that enhance transgene expression. This adaptability makes EBV vectors a valuable tool in both research and clinical settings [23].
Research on alpha herpes virus has significantly improved several genetic techniques, and EBV replication is comparable to that of other herpes viruses. However, EBV is distinct from alpha herpes viruses in that it induces latency in human B cells and modifies their growth [24].
EBV vectors with OriP-containing plasmid replicate once throughout the cell cycle in parallel with the host chromosomes. The high-affinity matrix attachment area containing oriP is responsible for anchoring EBV vectors, which have a chromatin-like structure, to the nuclear matrix in latently infected cells.
The two noncontiguous portions that make up OriP are the dyad symmetry (DS) element and the family of repetitions (FR). A 30-bp repeat sequence is present in 20 tandem flawed copies in the FR and four similar copies in the DS, the other region. The majority of sequences for EBNA1 binding are present in these 30-bp repeats.
With the use of EBV-based vectors, deficient human cell lines can be effectively corrected by cDNA or genomic DNA transfections leading to complementation and cloning of the correcting gene. It is possible to target tumor cells that express EBNA-1 specifically with vectors containing only oriP in EBV-associated neoplasms such as nasopharyngeal carcinoma and Burkitt’s lymphoma [25].
1.7 Retrovirus Vectors
Gene therapy commonly uses viruses, specifically retroviruses, as vectors. The genetic material found in retroviruses is RNA. Reverse transcription is the process by which the retrovirus converts RNA into DNA once it enters the host cell. The provirus, which is the viral DNA that has been created, is integrated into the host cell’s DNA. Proviruses often provide no risk to users. There is a significant risk, though, as some retroviruses have the ability to turn healthy cells malignant.
Retroviruses must render them harmless prior to using them as a vector. For instance, by deliberately deleting a gene that codes for the viral envelope, the retrovirus can be made inert. A retrovirus cannot enter the host cell if it does not have the envelope. A single envelope-defective retrovirus can multiply into many viral particles with the help of helper viruses. Helper viruses possess the usual genes that produce envelopes. Because the vector virus has a malfunctioning envelope gene, it can multiply together with the helper virus when it infects host cells (Figure 1.2). The vector and helper viruses multiply billions of times by repeatedly replicating in the host cells. It is possible to isolate and purify the vector viruses from the helper viruses. It is crucial to isolate vector viruses and ensure they are completely free of helper viruses. The health of patients receiving gene therapy is seriously threatened by helper virus contamination.
Figure 1.2 Large-scale production of vector viruses using helper viruses.
A retroviral vector carrying a maximum 8-kb size therapeutic DNA is useful for transforming the cells. However, the integration and delivery efficiency of therapeutic DNA is poor. To achieve high efficiency of integration, packaged retroviral RNA particles are used.
1.8 Lentivirus Vectors
Lentiviruses are among the most popular and useful viral vectors in the laboratory. Lentiviruses have two advantages: they have a large genetic capacity and can transduce both proliferating and nondividing cells. At the beginning of the 1990s, investigators developed viral vector systems based on retroviruses, such as the Moloney murine leukemia virus (MMLV).
Only actively dividing cells were susceptible to infection by the vectors, but they also had the ability to integrate into the genome and support transgenic expression for a long time. While nondividing cells might be infected by a different type of adenovirus-based vector, transgenic expression would not be produced over time. The packaging, envelope, and transfer plasmids constituted the original lentiviral vector system. The HIV-1 provirus mutant included in the packaging plasmid was unable to package itself because it lacked a few necessary proteins. The cell types that the vector could infect were determined by the viral envelope present on the envelope plasmid. Finally, the necessary transgene and HIV-1 longterminal repeats (LTRs) were included in the transfer plasmid, helping to facilitate the integration of the virus into the host genome. After these plasmids were co-transfected, 293T cells released transgene-containing lentiviral particles into the medium, which could be collected for use in research. Lentiviral vectors are still widely used for tracing and targeting brain cells because they can carry a significantly larger genetic cargo (8 kb versus 4.5 kb) than adeno-associated viral vectors, even though the latter can also target nondividing cells (Figure 1.3) [26, 27].
Lentiviruses have been studied for decades by researchers. Because it naturally inserts genetic material into cells, especially stem cells, HIV is the most well-known lentivirus. The lentiviral vector is built using an HIV virus blueprint. The HIV virus is made up of nine genes. Researchers take three or four different genes from the HIV virus’s blueprint to create the lentiviral vector, which increases the vector’s ability to transfer genetic material. Now, more genes will be added in order to produce the desired therapeutic effect. Since only a small portion of the nine genes from the original viral blueprint are used, HIV infection is impossible due to incomplete genomes.
Figure 1.3 HIV genome and lentiviral vector.
Lentiviral vectors, which are derived from the human immunodeficiency virus, have been extensively researched and improved during the past 20 years. To treat hemoglobinopathies and primary immunodeficiencies, third-generation, self-inactivating lentiviral vectors have been used in several clinical trials recently to transfer genes into hematopoietic stem cells (Figure 1.4). Furthermore, in order to create immunity against cancer, these vectors have been utilized to clone T cell receptors or introduce chimeric antigen receptors (CARs) into mature T cells. After CAR T cell therapies developed with lentiviral vectors demonstrated substantial clinical effectiveness in patients with B cell malignancies, regulators approved the first genetically modified cellular therapy [28].
1.9 Adeno-Associated Virus (AAV)
AAV is one of the gene therapy vehicles that is currently undergoing the most research. It was first discovered to be a contamination of viral preparations, which is where its name originates. A protein shell encloses and protects the 4.8-kb ssDNA genome that composes up AAV. AAV is a member of the parvovirus family [29].
Figure 1.4 Lentiviral vector in gene therapy.
Its ss genome has three genes: aap (Assembly), Rep (Replication), and Cap (Capsid). The most important consideration when creating a decent rAAV vector is the packing size of the expression cassette that will be placed in between the two ITRs (inverted terminal repeats). It is widely accepted that, even for viral ITRs, anything under 5 kb works as a good point of origin. The rate of transgene recombination (truncations) or viral production yields is considerably reduced when rAAV vectors larger than packaging cassettes (5 kb) are attempted to be generated. AAV vectors are not designed to efficiently package long coding sequences. Using dual overlapping vector techniques can aid in changing the packing. In order to achieve transgene expression, the ss AAV-delivered transgene must be transformed into a ds transgene upon delivery to the nucleus, according to its biology. Self-complementary AAV is beneficial because it bypasses that process by using its ss packed genome to complement itself and generate a ds genome in the nucleus. In contrast to the vector’s decreased packaging capacity, transgene expression occurs more quickly.
AAV is a highly effective vector for effecting gene integration into the host cell chromosome and transporting the gene into both dividing and nondividing cells. Furthermore, the genes delivered through the AAV vector may exhibit persistent expression. Using the AAV vector as a mediator, the prospect of introducing a gene into EBV-transformed B cells is investigated. The genes 6A8 and 5D4, which code for α-mannosidase and a cell membrane protein, respectively, were chosen for examination [30, 31].
1.10 Applications of Viral Vectors
1.10.1 Viral Vectors for Vaccine Development
The development of vaccines based on viral vectors has been steadily advancing, aiming to combat various malignancies as well as infectious disorders. In phase 3 trials, safety has been demonstrated for a number of vaccine candidates based on chimeric vesicular stomatitis virus (VSV) vectors. VSV-ZEBOV vector–based EBOV vaccine was approved by the FDA with the brand name Ervebo in 2019. GM-CSF–expressing oncolytic HSV-1 vector talimogene laherparepvec was approved by the FDA in 2015 for the treatment of metastatic melanoma.
For various vector systems, effective packaging cell line technologies have been developed to enable the quick and effective large-scale manufacturing of vaccine candidates suitable for clinical use [32].
1.10.2 Gene Therapy: The Performance of Viral Vectors
Promising in treating a wide range of diseases, gene therapies are presently among the most researched therapeutic approaches in both the clinical and preclinical phases. Gene therapies are a promising means of treating diseases that were previously thought to be incurable by traditional methods. It works by inserting a gene into target cells. A vector is frequently needed to transfer gene therapies into target cells; viral vectors are among the most researched vectors because of their unique benefits, including exceptional transduction efficiency. After decades of research and development, viral vector–based gene treatments have shown promise in the clinic, with multiple drugs now approved for the treatment of various infectious diseases, cancer, and monogenic disorders [33, 34].
In gene therapy, a vector is used to deliver genetic material to the cells. The molecules that make up genetic material, known as DNA or RNA, are responsible for storing information and sending instructions to the cells on what to do. It might include directions on how to make a certain protein, for instance.
Viral vectors are devices that are used in genetic engineering and molecular biology to introduce genetic material into cells. These viruses have been modified such that they can be utilized to transfer particular genes into the target cells. As a part of their normal life cycle, viruses have acquired the capacity to effectively transfer their genetic information into host cells.
Genome editing techniques have rapidly evolved, with CRISPR-Cas9 emerging as a leading method due to its precision, efficacy, and efficiency. This system relies on the collaboration of clustered regularly interspaced short palindromic repeats (CRISPR) and their associated protein, Cas9. The CRISPR/Cas9 system comprises two essential components: a Cas9 protein and a guide RNA (gRNA). A significant hurdle in therapeutic CRISPR/Cas9 applications has been the development of safe and efficient delivery methods. Viral vectors, renowned for their in vivo delivery capabilities, have emerged as promising candidates. Lentivirus vectors (LVs), AAVs, and AdVs are commonly employed due to their superior delivery efficiency compared to other methods [35].
1.10.3 Clinical Trials
Many therapeutic investigations utilizing viral vectors have been undertaken and are currently ongoing [32]. For instance, following three decades of development, pivotal-stage clinical studies for gene therapy for hemophilia are currently underway, which mainly focus on AAV-based vectors. There have been eleven clinical trials for hemophilia gene therapy, while with some degree of effectiveness, liver-directed AAV expressing either FVIII or FIX has been used in six ongoing phase 1/2 clinical trials [36, 37].
As reported by Carbonero et al., intravenous administration of enadenotucirev in patients with different cancers including colorectal cancer, urothelial cell cancer, non–small cell lung cancer, and renal cell cancer was studied. Enadenotucirev is a chimeric adenovirus that selectively targets tumors and has exhibited preclinical activity. This virus delivery was accompanied by significant local CD8+ cell infiltration in 80% of examined tumor samples, suggesting an enadenotucirev-driven immune response. In the majority of tumor samples, tumor-specific delivery was found, and there were no treatment-related significant side effects [38]. A phase 1 clinical trial with oncolytic VVs was also conducted in 11 patients with resistant advanced colorectal or other solid tumors [39]. Viral vectors under clinical trial are given in Table 1.1.
1.11 Safety Issues of Viral Vector/Biosafety Challenges
Although the introduction of viral vector gene delivery methods has resulted in a promising new chapter in gene therapy recently, not all cell types can be treated by a single delivery method, either in vitro or in vivo. Additionally, there are unique occupational health and safety issues associated with the use of viral vector systems. The safe use of viral vector systems in human gene therapy research is a concern shared by the majority of IBCs in research and clinical settings, as there is currently no single document outlining best practices for using them. Institutional biosafety committees (IBCs) and healthcare providers have limited resources when it comes to risk assessment and developing protocols to minimize risk and exposure in a research/clinical context [4].
Table 1.1 Viral vectors under clinical trial.
Viral vector
Disease
Outcome
Reference
Oncolytic HSV HF10
Different cancers
Antitumor activity, low adverse effects
[
40
]
Oncolytic HSV M032
Glioblastoma
Significant antitumor activity
[
41
]
NDV expressing multiple tumorassociated antigens (TAAs)
Ovarian, stomach, and pancreatic cancer
Long-term survival in phase 2 trials
[
42
]
CAV21
Melanoma
Antitumor activity
[
43
,
44
]
Lenti-FVIII
Hemophilia
Potential cure
[
38
]
AAV
Clinical investigations and preclinical animal research have shown that AAV vectors are extremely safe. Eighty percent of people have positive antibodies against AAV strains. Frequent doses, however, may be a limiting factor since it may trigger an immune response. Furthermore, a number of gene clinical studies have shown that AAV vectors do not induce an enhanced immune response. The incorporation of recombinant AAV enhanced the incidence of tumor formation in various animal models, although this connection has not been found in humans [4].
Adenovirus Vectors
Adenoviral genes are currently challenging to produce, even though their genomes have a carrying capacity of over 30 kb. Another problem with AdVs in general is that, unlike the relatively harmless AAV virions, the particles themselves cause cellular inflammatory responses [45, 46].
Retrovirus Vectors
Retroviral vectors have been widely employed to deliver therapeutic genes in the field of gene therapy and clinical applications for monogenic disorders, cancer, and infectious diseases, providing patients with steady and efficient transgene expression [4]. However, the greatest safety risk associated with the use of RV stems from their potential to integrate into the host cell genome, which elevates the chance of insertional mutagenesis and oncogene activation [47].
Lentivirus Vectors
Since lentiviral vectors are more effective at transducing non-proliferating or slowly proliferating cells—like CD34 stem cells—they have become more and more popular for use in therapeutic settings. However, there are still hazards associated with using LVVs in research, and evaluations are being done regarding the clinical procedures’ long-term safety. The limitations of using LVVs in clinical trials today result mostly from inadequate techniques for the production of high-titer virus stocks and safety concerns regarding their origin from HI, despite the engineering of packing cell lines and the removal of genes required for viral replication [4].
Some Other Challenges are as Follows:
Immunogenicity: The immune system may recognize and mount a response against the viral vectors, potentially limiting their effectiveness.
Insertional Mutagenesis: Some viral vectors may integrate into the host cell’s genome, which can lead to unintended consequences, such as activating or disrupting other genes.
Overexpression of target gene
Immune response to native protein or viral capsid
Hepatotoxicity
1.12 Conclusion
Gene therapy is a promising field that aims to introduce, replace, or alter genetic material within a person’s cells in order to treat or prevent disease. It is noteworthy that the selection of the viral vector is dependent upon a number of parameters, such as the intended duration of gene expression, the target tissue, and safety considerations. Therapeutic genes are delivered to target cells primarily by viral vectors. Many viral vectors exist, but retroviral and AdVs in particular, have shown great efficacy in transferring therapeutic genes to target cells. Viral vectors can either remain episomal (adenoviruses) or integrate into the host genome (retroviruses) in order to sustain gene expression. Despite their efficacy and safety, viral vectors can trigger immune responses in the host, leading to inflammation or the destruction of transduced cells. Insertional mutagenesis poses a concern since the integration of the viral genome into the host DNA can interfere with normal gene activity, particularly when using retroviral vectors. In gene therapy, viral vectors are useful tools, but more investigation and development are required to address safety issues, increase targeting specificity, and boost overall efficacy. In order to conduct competent research and apply gene therapy using viral vectors in the future, it will be necessary to balance potential benefits with ethical considerations.
References
1. Barrett, A.D.T. and Stanberry, L.R.,
Vaccines for biodefense and emerging and neglected diseases
, 1st ed., Academic Press/Elsevier, Amsterdam Boston, 2009.
2. Blaney, J.E., Matro, J.M., Murphy, B.R., Whitehead, S.S., Recombinant, Live-Attenuated Tetravalent Dengue Virus Vaccine Formulations Induce a Balanced, Broad, and Protective Neutralizing Antibody Response against Each of the Four Serotypes in Rhesus Monkeys.
J. Virol.
[Internet], 79, 9, 5516–5528, 2005, Available from:
https://journals.asm.org/doi/10.1128/JVI.79.9.5516-5528.2005
.
3. Chen, Y.H., Keiser, M.S., Davidson, B.L., Viral Vectors for Gene Transfer.
CP Mouse Biol.
[Internet], 8, 4, e58, 2018, Available from:
https://currentprotocols.onlinelibrary.wiley.com/doi/10.1002/cpmo.58
.
4. Ghosh, S., Brown, A.M., Jenkins, C., Campbell, K., Viral Vector Systems for Gene Therapy: A Comprehensive Literature Review of Progress and Biosafety Challenges.
Appl. Biosaf.
[Internet], 25, 1, 7–18, 2020, Available from:
https://www.liebertpub.com/doi/10.1177/1535676019899502
.
5. Madhan, S., Prabakaran, M., Kwang, J., Baculovirus as Vaccine Vectors.
CGT
[Internet], 10, 3, 201–213, 2010, Available from:
http://www.eurekaselect.com/openurl/content.php?genre=article&issn=1566-5232&volume=10&issue=3&spage=201
.
6. Schaly, S., Ghebretatios, M., Prakash, S., Baculoviruses in Gene Therapy and Personalized Medicine.
BTT
[Internet], 15, 115–132, 2021, Available from:
https://www.dovepress.com/baculoviruses-in-gene-therapy-and-personalizedmedicine-peer-reviewed-fulltext-article-BTT
.
7. Wold, W. and Toth, K., Adenovirus Vectors for Gene Therapy, Vaccination and Cancer Gene Therapy.
CGT
[Internet], 13, 6, 421–433, 2014, Available from:
http://www.eurekaselect.com/openurl/content.php?genre=article&issn=1566-5232&volume=13&issue=6&spage=421
.
8. Chavda, V.P., Ghali, E.N.H.K., Balar, P.C.,
et al.
, Protein subunit vaccines: Promising frontiers against COVID-19.
J. Control. Release
, 366, 761–782, 2024.
9. El-Maradny, Y.A., Ramadan, A.A., Chavda, V.P., Balar, P.C., Redwan, E.M., The fast-track development of COVID-19 vaccines [Internet], in:
Advanced Vaccination Technologies for Infectious and Chronic Diseases
, pp. 415–440, Elsevier, Amsterdam, Netherlands, 2024, [cited 2024 May 31], Available from:
https://linkinghub.elsevier.com/retrieve/pii/B9780443185649000278
.
10. Mendonça, S.A., Lorincz, R., Boucher, P., Curiel, D.T., Adenoviral vector vaccine platforms in the SARS-CoV-2 pandemic.
npj Vaccines
[Internet], 6, 1, 97, 2021, Available from:
https://www.nature.com/articles/s41541-021-00356-x
.
11. Coughlan, L., Factors Which Contribute to the Immunogenicity of Nonreplicating Adenoviral Vectored Vaccines.
Front. Immunol.
[Internet], 11, 909, 2020, Available from:
https://www.frontiersin.org/article/10.3389/fimmu.2020.00909/full
.
12. Chavda, V.P., Teli, D., Balar, P.C.,
et al.
, Potential Anti-SARS-CoV-2 Prodrugs Activated by Phosphorylation and Their Role in the Aged Population.
Molecules
, 28, 5, 2332, 2023.
13. Chavda, V.P., Vuppu, S., Mishra, T., Balar, P., The Emergence of Hybrid Variants of SARS-CoV-2: Towards Hybrid Immunity.
Vaccines
, 11, 4, 764, 2023.
14. Sayedahmed, E.E., Kumari, R., Mittal, S.K., Current Use of Adenovirus Vectors and Their Production Methods [Internet], in:
Viral Vectors for Gene Therapy
, F.P. Manfredsson and M.J. Benskey (Eds.), pp. 155–175, Springer New York, New York, NY, 2019, [cited 2023 Dec 11]. Available from:
http://link.springer.com/10.1007/978-1-4939-9065-8_9
.
15. Matsunaga, W. and Gotoh, A., Adenovirus as a Vector and Oncolytic Virus.
CIMB
[Internet], 45, 6, 4826–4840, 2023, Available from:
https://www.mdpi.com/1467-3045/45/6/307
.
16. Zhang, W.-W., Li, L., Li, D.,
et al.
, The First Approved Gene Therapy Product for Cancer Ad
p53
(Gendicine): 12 Years in the Clinic.
Hum. Gene Ther.
[Internet], 29, 2, 160–179, 2018, Available from:
http://www.liebertpub.com/doi/10.1089/hum.2017.218
.
17. Krauzewicz, N. and Griffin, B.E., Polyoma and Papilloma Virus Vectors For Cancer Gene Therapy [Internet], in:
Cancer Gene Therapy
, N.A. Habib (Ed.), pp. 73–82, Springer US, New York, NY, 2002, [cited 2023 Dec 11]. Available from:
http://link.springer.com/10.1007/0-306-46817-4_8
.
18. Poxvirus, Description, Types, Features, & Disease, Britannica [Internet], Available from:
https://www.britannica.com/science/poxvirus
.
19. Carroll, M.W. and Moss, B., Poxviruses as expression vectors.
Curr. Opin. Biotechnol.
[Internet], 8, 5, 573–577, 1997, Available from:
https://linkinghub.elsevier.com/retrieve/pii/S0958166997800316
.
20. Vera, M. and Fortes, P., Simian Virus-40 as a Gene Therapy Vector.
DNA Cell Biol.
[Internet], 23, 5, 271–282, 2004, Available from:
http://www.liebertpub.com/doi/10.1089/104454904323090903
.
21. Artusi, S., Miyagawa, Y., Goins, W., Cohen, J., Glorioso, J., Herpes Simplex Virus Vectors for Gene Transfer to the Central Nervous System.
Diseases
[Internet], 6, 3, 74, 2018, Available from:
http://www.mdpi.com/2079-9721/6/3/74
.
22. Kamel, M. and El-Sayed, A., Utilization of herpesviridae as recombinant viral vectors in vaccine development against animal pathogens.
Virus Res.
[Internet], 270, 197648, 2019, Available from:
https://linkinghub.elsevier.com/retrieve/pii/S016817021930005X
.
23. Kiyosue, K. and Miwa, Y., Epstein-Barr virus-derived vector suitable for longterm expression in neurons.
Heliyon
[Internet], 6, 3, e03504, 2020, Available from:
https://linkinghub.elsevier.com/retrieve/pii/S2405844020303492
.
24. (NAS Colloquium),
Genetic Engineering of Viruses and Viral Vectors
[Internet], National Academies Press, Washington, D.C., 1996, Available from:
http://www.nap.edu/catalog/5708
.
25. Van Craenenbroeck, K., Vanhoenacker, P., Haegeman, G., Episomal vectors for gene expression in mammalian cells.
Eur. J. Biochem.
[Internet], 267, 18, 5665–5678, 2000, Available from:
https://febs.onlinelibrary.wiley.com/doi/10.1046/j.1432-1327.2000.01645.x
.
26. Dong, W. and Kantor, B., Lentiviral Vectors for Delivery of GeneEditing Systems Based on CRISPR/Cas: Current State and Perspectives.
Viruses
[Internet], 13, 7, 1288, 2021, Available from:
https://www.mdpi.com/1999-4915/13/7/1288
.
27. Zufferey, R., Dull, T., Mandel, R.J.,
et al.
, Self-Inactivating Lentivirus Vector for Safe and Efficient
In Vivo
Gene Delivery.
J. Virol.
[Internet], 72, 12, 9873–9880, 1998, Available from:
https://journals.asm.org/doi/10.1128/JVI.72.12.9873-9880.1998
.
28. Milone, M.C. and O’Doherty, U., Clinical use of lentiviral vectors.
Leukemia
[Internet], 32, 7, 1529–1541, 2018, Available from:
https://www.nature.com/articles/s41375-018-0106-0
.
29. Kaplitt, M.G. and Loewy, A.D.,
Viral Vectors: Gene Therapy and Neuroscience Applications
, Academic Press, San Diego, California, USA, 1995.
30. Shi, G.X., Wang, Y., Liu, Y., Cui, W., Zhao, F.T., Zhu, L.P., Long-Term Expression of a Transferred Gene in Epstein–Barr Virus Transformed Human B Cells.
Scand. J. Immunol.
[Internet], 54, 3, 265–272, 2001, Available from:
https://onlinelibrary.wiley.com/doi/10.1046/j.1365-3083.2001.00924.x
.
31. Grieger, J.C., Choi, V.W., Samulski, R.J., Production and characterization of adeno-associated viral vectors.
Nat. Protoc.
[Internet], 1, 3, 1412–1428, 2006, Available from:
https://www.nature.com/articles/nprot.2006.207
.
32. Lundstrom, K., Application of Viral Vectors for Vaccine Development with a Special Emphasis on COVID-19.
Viruses
[Internet], 12, 11, 1324, 2020, Available from:
https://www.mdpi.com/1999-4915/12/11/1324
.
33. Li, X., Le, Y., Zhang, Z., Nian, X., Liu, B., Yang, X., Viral Vector-Based Gene Therapy.
IJMS
[Internet], 24, 9, 7736, 2023, Available from:
https://www.mdpi.com/1422-0067/24/9/7736
.
34. Zhao, Z., Anselmo, A.C., Mitragotri, S., Viral vector-based gene therapies in the clinic.
Bioeng. Transl. Med.
[Internet], 7, 1, e10258, 2022, Available from:
https://aiche.onlinelibrary.wiley.com/doi/10.1002/btm2.10258
.
35. Asmamaw Mengstie, M., Viral Vectors for the
in Vivo
Delivery of CRISPR Components: Advances and Challenges.
Front. Bioeng. Biotechnol.
[Internet], 10, 895713, 2022, Available from:
https://www.frontiersin.org/articles/10.3389/fbioe.2022.895713/full
.
36. Spencer, H.T., Riley, B.E., Doering, C.B., State of the art: gene therapy of haemophilia.
Haemophilia
[Internet], 22, S5, 66–71, 2016, Available from:
https://onlinelibrary.wiley.com/doi/10.1111/hae.13011
.
37. Mingozzi, F. and High, K.A., Immune responses to AAV vectors: Overcoming barriers to successful gene therapy.
Blood
[Internet], 122, 1, 23–36, 2013, Available from:
https://ashpublications.org/blood/article/122/1/23/31570/Immune-responses-to-AAV-vectors-overcoming
.
38. Garcia-Carbonero, R., Salazar, R., Duran, I.,
et al.
, Phase 1 study of intravenous administration of the chimeric adenovirus enadenotucirev in patients undergoing primary tumor resection.
J. Immunother. Cancer
[Internet], 5, 1, 71, 2017, Available from:
https://jitc.bmj.com/lookup/doi/10.1186/s40425-017-0277-7
.
39. Downs-Canner, S., Guo, Z.S., Ravindranathan, R.,
et al.
, Phase 1 Study of Intravenous Oncolytic Poxvirus (vvDD) in Patients With Advanced Solid Cancers.
Mol. Ther.
[Internet], 24, 8, 1492–1501, 2016, Available from:
https://linkinghub.elsevier.com/retrieve/pii/S1525001616336012
.
40. Eissa, I.R., Naoe, Y., Bustos-Villalobos, I.,
et al.
, Genomic Signature of the Natural Oncolytic Herpes Simplex Virus HF10 and Its Therapeutic Role in Preclinical and Clinical Trials.
Front. Oncol.
[Internet], 7, 149, 2017, Available from:
http://journal.frontiersin.org/article/10.3389/fonc.2017.00149/full
.
41. Markert, J.M., Razdan, S.N., Kuo, H.-C.,
et al.
, A Phase 1 Trial of Oncolytic HSV-1, G207, Given in Combination With Radiation for Recurrent GBM Demonstrates Safety and Radiographic Responses.
Mol. Ther.
[Internet], 22, 5, 1048–1055, 2014, Available from:
https://linkinghub.elsevier.com/retrieve/pii/S1525001616312369
.
42. Schirrmacher, V., Clinical trials of antitumor vaccination with an autologous tumor cell vaccine modified by virus infection: Improvement of patient survival based on improved antitumor immune memory.
Cancer Immunol. Immunother.
[Internet], 54, 6, 587–598, 2005, Available from:
http://link.springer.com/10.1007/s00262-004-0602-0
.
43. Pandha, H., Harrington, K., Ralph, C., Melcher, A., Grose, M., Shafren, D., Phase I/II storm study: Intravenous delivery of a novel oncolytic immunotherapy agent, Coxsackievirus A21, in advanced cancer patients.
J. Immunother. Cancer
[Internet], 3, Suppl 2, P341, 2015, Available from:
https://jitc.bmj.com/lookup/doi/10.1186/2051-1426-3-S2-P341
.
44. Andtbacka, R.H., Curti, B.D., Hallmeyer, S.,
et al.
, Phase II calm extension study: Coxsackievirus A21 delivered intratumorally to patients with advanced melanoma induces immune-cell infiltration in the tumor microenvironment.
J. Immunother. Cancer
[Internet], 3, Suppl 2, P343, 2015, Available from:
https://jitc.bmj.com/lookup/doi/10.1186/2051-1426-3-S2-P343
.
45. Lowenstein, P., Mandel, R., Xiong, W., Kroeger, K., Castro, M., Immune Responses to Adenovirus and Adeno-Associated Vectors Used for Gene Therapy of Brain Diseases: The Role of Immunological Synapses in Understanding the Cell Biology of Neuroimmune Interactions.
CGT
[Internet], 7, 5, 347–360, 2007, Available from:
http://www.eurekaselect.com/openurl/content.php?genre=article&issn=1566-5232&volume=7&issue=5&spage=347
.
46. Morsy, M.A. and Caskey, C.T., Expanded-capacity adenoviral vectors— the helper-dependent vectors.
Mol. Med. Today
[Internet], 5, 1, 18–24, 1999, Available from:
https://linkinghub.elsevier.com/retrieve/pii/S1357431098013768
.
47. Romano, G., Development of Safer Gene Delivery Systems to Minimize the Risk of Insertional Mutagenesis-Related Malignancies: A Critical Issue for the Field of Gene Therapy.
ISRN Oncol.
[Internet], 2012, 1–14, 2012, Available from:
https://www.hindawi.com/journals/isrn/2012/616310/
.
Note
*
Corresponding author
:
