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Viruses
Special Issues
New Aspects of Adenoviral Vaccine Vectors and Adenoviral Gene Therapy
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New Aspects of Adenoviral Vaccine Vectors and Adenoviral Gene Therapy

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 15670

Special Issue Editors

Prof. Dr. Thomas Dobner

E-Mail Website
Guest Editor
Department of Viral Transformation, Leibniz Institute for Experimental Virology (HPI), Hamburg, Germany
Interests: adenoviruses; mechanisms of viral replication; viral transformation
Dr. Luca Bertzbach

E-Mail Website
Guest Editor
Department of Viral Transformation, Leibniz Institute for Experimental Virology (HPI), Hamburg, Germany
Interests: virus-host interactions; DNA viruses; viral oncogenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

Adenoviruses are commonly used as efficient high-capacity vectors and as excellent gene delivery vehicles. Their applications range from basic molecular research to gene therapy and viral vector vaccines. Adenoviral vectors are currently being used in regenerative and cancer therapies and, most importantly, as vaccines such as in first-generation COVID-19 vaccines. Despite widespread applications and constant progress, various challenges and safety concerns still limit using adenoviral vectors to their full potential. Our Special Issue will publish original research articles and reviews that include, but are not limited to, investigations on (cross-species) adenoviral vector development, viral persistence and genomic integration, adenoviral tissue tropism, and relevant studies on adenoviral biology. Together, this collection of articles will provide new aspects of adenoviral vectors and their applications in vaccine and gene therapy settings.

We’re looking forward to reading your contributions!

Prof. Dr. Thomas Dobner
Dr. Luca Bertzbach
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • adenovirus
  • viral vector vaccine
  • gutless vectors
  • high-capacity vectors
  • transgene expression
  • cancer therapy
  • oncolytic vectors

Published Papers (6 papers)

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Editorial

Jump to: Research, Review

2 pages, 156 KiB  
Editorial
Updates and New Perspectives on Adenoviral Gene Therapy and Vaccine Vectors
by Thomas Dobner and Luca D. Bertzbach
Viruses 2023, 15(2), 514; https://0-doi-org.brum.beds.ac.uk/10.3390/v15020514 - 13 Feb 2023
Viewed by 1483
Abstract
Adenoviruses are commonly used as efficient high-capacity vectors and excellent gene delivery vehicles [...] Full article
(This article belongs to the Special Issue New Aspects of Adenoviral Vaccine Vectors and Adenoviral Gene Therapy)

Research

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17 pages, 6012 KiB  
Article
A Single Oral Immunization with Replication-Competent Adenovirus-Vectored Vaccine Induces a Neutralizing Antibody Response in Mice against Canine Distemper Virus
by Xiang Du, Emeline Goffin, Lucie Gillard, Bénédicte Machiels and Laurent Gillet
Viruses 2022, 14(9), 1847; https://0-doi-org.brum.beds.ac.uk/10.3390/v14091847 - 23 Aug 2022
Cited by 3 | Viewed by 1922
Abstract
Canine Distemper Virus (CDV) is a fatal and highly contagious pathogen of multiple carnivores. While injectable vaccines are very effective in protecting domestic animals, their use in the wild is unrealistic. Alternative vaccines are therefore needed. Adenovirus (AdV) vectors are popular vaccine vectors [...] Read more.
Canine Distemper Virus (CDV) is a fatal and highly contagious pathogen of multiple carnivores. While injectable vaccines are very effective in protecting domestic animals, their use in the wild is unrealistic. Alternative vaccines are therefore needed. Adenovirus (AdV) vectors are popular vaccine vectors due to their capacity to elicit potent humoral and cellular immune responses against the antigens they carry. In parallel, vaccines based on live human AdV-4 and -7 have been used in U.S. army for several decades as replicative oral vaccines against respiratory infection with the same viruses. Based on these observations, the use of oral administration of replication competent AdV-vectored vaccines has emerged as a promising tool especially for wildlife vaccination. Developing this type of vaccine is not easy, however, given the high host specificity of AdVs and their very low replication in non-target species. To overcome this problem, the feasibility of this approach was tested using mouse adenovirus 1 (MAV-1) in mice as vaccine vectors. First, different vaccine vectors expressing the entire or part H or F proteins of CDV were constructed. These different strains were then used as oral vaccines in BALB/c mice and the immune response to CDV was evaluated. Only the strain expressing the full length CDV H protein generated a detectable and neutralizing immune response to CDV. Secondly, using this strain, we were able to show that although this type of vaccine is sensitive to pre-existing immunity to the vector, a second oral administration of the same vaccine is able to boost the immune response against CDV. Overall, this study demonstrates the feasibility of using replicating AdVs as oral vaccine vectors to immunize against CDV in wildlife carnivores. Full article
(This article belongs to the Special Issue New Aspects of Adenoviral Vaccine Vectors and Adenoviral Gene Therapy)
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19 pages, 2936 KiB  
Article
Properties of Adenovirus Vectors with Increased Affinity to DSG2 and the Potential Benefits of Oncolytic Approaches and Gene Therapy
by Nora A. Bahlmann, Raphael L. Tsoukas, Sebastian Erkens, Hongjie Wang, Franziska Jönsson, Malik Aydin, Ella A. Naumova, André Lieber, Anja Ehrhardt and Wenli Zhang
Viruses 2022, 14(8), 1835; https://0-doi-org.brum.beds.ac.uk/10.3390/v14081835 - 21 Aug 2022
Cited by 5 | Viewed by 2149
Abstract
Carcinomas are characterized by a widespread upregulation of intercellular junctions that create a barrier to immune response and drug therapy. Desmoglein 2 (DSG2) represents such a junction protein and serves as one adenovirus receptor. Importantly, the interaction between human adenovirus type 3 (Ad3) [...] Read more.
Carcinomas are characterized by a widespread upregulation of intercellular junctions that create a barrier to immune response and drug therapy. Desmoglein 2 (DSG2) represents such a junction protein and serves as one adenovirus receptor. Importantly, the interaction between human adenovirus type 3 (Ad3) and DSG2 leads to the shedding of the binding domain followed by a decrease in the junction protein expression and transient tight junction opening. Junction opener 4 (JO-4), a small recombinant protein derived from the Ad3 fiber knob, was previously developed with a higher affinity to DSG2. JO-4 protein has been proven to enhance the effects of antibody therapy and chemotherapy and is now considered for clinical trials. However, the effect of the JO4 mutation in the context of a virus remains insufficiently studied. Therefore, we introduced the JO4 mutation to various adenoviral vectors to explore their infection properties. In the current experimental settings and investigated cell lines, the JO4-containing vectors showed no enhanced transduction compared with their parental vectors in DSG2-high cell lines. Moreover, in DSG2-low cell lines, the JO4 vectors presented a rather weakened effect. Interestingly, DSG2-negative cell line MIA PaCa-2 even showed resistance to JO4 vector infection, possibly due to the negative effect of JO4 mutation on the usage of another Ad3 receptor: CD46. Together, our observations suggest that the JO4 vectors may have an advantage to prevent CD46-mediated sequestration, thereby achieving DSG2-specific transduction. Full article
(This article belongs to the Special Issue New Aspects of Adenoviral Vaccine Vectors and Adenoviral Gene Therapy)
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Review

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16 pages, 560 KiB  
Review
A Renaissance for Oncolytic Adenoviruses?
by Paola Blanchette and Jose G. Teodoro
Viruses 2023, 15(2), 358; https://0-doi-org.brum.beds.ac.uk/10.3390/v15020358 - 26 Jan 2023
Cited by 9 | Viewed by 2439
Abstract
In the 1990s, adenovirus became one of the first virus types to be genetically engineered to selectively destroy cancer cells. In the intervening years, the field of “oncolytic viruses” has slowly progressed and culminated in 2015 with the FDA approval of Talimogene laherparepvec, [...] Read more.
In the 1990s, adenovirus became one of the first virus types to be genetically engineered to selectively destroy cancer cells. In the intervening years, the field of “oncolytic viruses” has slowly progressed and culminated in 2015 with the FDA approval of Talimogene laherparepvec, a genetically engineered herpesvirus, for the treatment of metastatic melanoma. Despite the slower progress in translating oncolytic adenovirus to the clinic, interest in the virus remains strong. Among all the clinical trials currently using viral oncolytic agents, the largest proportion of these are using recombinant adenovirus. Many trials are currently underway to use oncolytic virus in combination with immune checkpoint inhibitors (ICIs), and early results using oncolytic adenovirus in this manner are starting to show promise. Many of the existing strategies to engineer adenoviruses were designed to enhance selective tumor cell replication without much regard to interactions with the immune system. Adenovirus possesses a wide range of viral factors to attenuate both innate anti-viral pathways and immune cell killing. In this review, we summarize the strategies of oncolytic adenoviruses currently in clinical trials, and speculate how the mutational backgrounds of these viruses may impact upon the efficacy of these agents in oncolytic and immunotherapy. Despite decades of research on human adenoviruses, the interactions that these viruses have with the immune system remains one of the most understudied aspects of the virus and needs to be improved to rationally design the next generation of engineered viruses. Full article
(This article belongs to the Special Issue New Aspects of Adenoviral Vaccine Vectors and Adenoviral Gene Therapy)
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14 pages, 1677 KiB  
Review
The Adenovirus Vector Platform: Novel Insights into Rational Vector Design and Lessons Learned from the COVID-19 Vaccine
by Erwan Sallard, Wenli Zhang, Malik Aydin, Katrin Schröer and Anja Ehrhardt
Viruses 2023, 15(1), 204; https://0-doi-org.brum.beds.ac.uk/10.3390/v15010204 - 11 Jan 2023
Cited by 10 | Viewed by 3994
Abstract
The adenovirus vector platform remains one of the most efficient toolboxes for generation of transfer vehicles used in gene therapy and virotherapy to treat tumors, as well as vaccines to protect from infectious diseases. The adenovirus genome and capsids can be modified using [...] Read more.
The adenovirus vector platform remains one of the most efficient toolboxes for generation of transfer vehicles used in gene therapy and virotherapy to treat tumors, as well as vaccines to protect from infectious diseases. The adenovirus genome and capsids can be modified using highly efficient techniques, and vectors can be produced at high titers, which facilitates their rapid adaptation to current needs and disease applications. Over recent years, the adenovirus vector platform has been in the center of attention for vaccine development against the ongoing coronavirus SARS-CoV-2/COVID-19 pandemic. The worldwide deployment of these vaccines has greatly deepened the knowledge on virus-host interactions and highlighted the need to further improve the effectiveness and safety not only of adenovirus-based vaccines but also of gene therapy and oncolytic virotherapy vectors. Based on the current evidence, we discuss here how adenoviral vectors can be further improved by intelligent molecular design. This review covers the full spectrum of state-of-the-art strategies to avoid vector-induced side effects ranging from the vectorization of non-canonical adenovirus types to novel genome engineering techniques. Full article
(This article belongs to the Special Issue New Aspects of Adenoviral Vaccine Vectors and Adenoviral Gene Therapy)
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21 pages, 3181 KiB  
Review
Significance of Preexisting Vector Immunity and Activation of Innate Responses for Adenoviral Vector-Based Therapy
by Wen-Chien Wang, Ekramy E. Sayedahmed and Suresh K. Mittal
Viruses 2022, 14(12), 2727; https://0-doi-org.brum.beds.ac.uk/10.3390/v14122727 - 06 Dec 2022
Cited by 7 | Viewed by 2644
Abstract
An adenoviral (AdV)-based vector system is a promising platform for vaccine development and gene therapy applications. Administration of an AdV vector elicits robust innate immunity, leading to the development of humoral and cellular immune responses against the vector and the transgene antigen, if [...] Read more.
An adenoviral (AdV)-based vector system is a promising platform for vaccine development and gene therapy applications. Administration of an AdV vector elicits robust innate immunity, leading to the development of humoral and cellular immune responses against the vector and the transgene antigen, if applicable. The use of high doses (1011–1013 virus particles) of an AdV vector, especially for gene therapy applications, could lead to vector toxicity due to excessive levels of innate immune responses, vector interactions with blood factors, or high levels of vector transduction in the liver and spleen. Additionally, the high prevalence of AdV infections in humans or the first inoculation with the AdV vector result in the development of vector-specific immune responses, popularly known as preexisting vector immunity. It significantly reduces the vector efficiency following the use of an AdV vector that is prone to preexisting vector immunity. Several approaches have been developed to overcome this problem. The utilization of rare human AdV types or nonhuman AdVs is the primary strategy to evade preexisting vector immunity. The use of heterologous viral vectors, capsid modification, and vector encapsulation are alternative methods to evade vector immunity. The vectors can be optimized for clinical applications with comprehensive knowledge of AdV vector immunity, toxicity, and circumvention strategies. Full article
(This article belongs to the Special Issue New Aspects of Adenoviral Vaccine Vectors and Adenoviral Gene Therapy)
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