Adenovirus vector induced innate immune responses: impact upon efficacy and toxicity in gene therapy and vaccine applications.
Open accessAbstract
Extensively characterized, modified, and employed for a variety of purposes, adenovirus (Ad) vectors are generally regarded as having great potential by many applied virologists who wish to manipulate and use viral biology to achieve beneficial clinical outcomes. Despite widespread functional prominence and utility (i.e., Ad-based clinical trials have begun to progress to critical Phase III levels, it has recently become apparent that investigations regarding the innate immune response to Ads may reveal not only reasons behind previous failures, but also reveal novel insights that will allow for safer, more efficacious uses of this important gene transfer platform. Insights gained by the exploration of Ad induced innate immune responses will likely be most important to the fields of vaccine development, since Ad-based vaccines are regarded as one of the more promising vaccine platforms in development today. Adenovirus is currently known to interact with several different extracellular, intracellular, and membrane-bound innate immune sensing systems. Past and recent studies involving manipulation of the Ad infectious cycle as well as use of different mutants have shed light on some of the initiation mechanisms underlying Ad induced immune responses. More recent studies using microarray-based analyses, genetically modified cell lines and/or mouse mutants, and advanced generation Ad vectors have revealed important new insights into the scope and mechanism of this cellular defensive response. This review is an attempt to synthesize these studies, update Ad biologists to the current knowledge surrounding these increasingly important issues, as well as highlight areas where future research should be directed. It should also serve as a sobering reality to researchers exploring the use of any gene transfer vector, as to the complexities potentially involved when contemplating use of such vectors for human applications.
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Antigen non-specific stimulation of type I interferon pathways has been demonstrated with other mRNA formulations in animal models.
“however, antigen non-specific stimulation of type I interferon pathways has been demonstrated with other formulations of mRNA in animal models78,79.”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [78]
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- Authors
- Hartman, Z. C., Appledorn, D. M., & Amalfitano, A.
- Affiliations
- Duke Medical Center (US)
- Michigan State University (US)
- Corresponding author
- Amalfitano, Andrea
- ORCID
- Hartman, Zachary C.
- Venue
- Virus Research
- Publisher
- Elsevier BV
- Published
- 2008-03
- Volume
- 132
- Issue
- 1-2
- Pages
- 1-14
- ISSN
- 0168-1702 (ISSN-L)
- PMC
- PMC4039020
- OpenAlex
- W2075338937
- Cited by
- 239
- References
- 101
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 6 · 2023: 9 · 2022: 6 · 2021: 14 · 2020: 13 · 2019: 8 · 2018: 6 · 2017: 14 · 2016: 3 · 2015: 11 · 2014: 14 · 2013: 17 · 2012: 15
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Virus Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (P01CA078673, CA078673)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK069884, R01DK069884)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- adenoviral vector, innate immune response, gene therapy, vaccine development, adjuvants, immune evasion, gene delivery vectors, vector toxicity
- MeSH terms
- Adenoviridae, Animals, Genetic Vectors, Humans, Immunity, Innate, Receptors, Virus, Viral Vaccines, Genetic Therapy, Mice
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