The DOI matches its Crossref record; 101 of the 109 references it cites were found in a registry or an index, and 8 are not checked yet.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 Gene
Poltorak, A., He, X., Smirnova, I., Liu, M.-Y., Huffel, C. V., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., et al. (1998) · Science · doi:10.1126/science.282.5396.2085 · Cited by 7,631
Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses
Kato, H., Takeuchi, O., Sato, S., Yoneyama, M., Yamamoto, M., Matsui, K., Uematsu, S., Jung, A., Kawai, T., Ishii, K. J., et al. (2006) · Nature · doi:10.1038/nature04734 · Cited by 3,888
Phylogenetic Perspectives in Innate Immunity
Hoffmann, J. A., Kafatos, F. C., Janeway, C. A., & Ezekowitz, R. A. B. (1999) · Science · doi:10.1126/science.284.5418.1313 · Cited by 2,524
Decoding the Patterns of Self and Nonself by the Innate Immune System
Medzhitov, R., & Janeway, C. A. (2002) · Science · doi:10.1126/science.1068883 · Cited by 2,154
VISA Is an Adapter Protein Required for Virus-Triggered IFN-β Signaling
Xu, L., Wang, Y., Han, K.-J., Li, L., Zhai, Z., & Shu, H. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.08.014 · Cited by 1,849
Innate immune sensing and its roots: the story of endotoxin
Beutler, B., & Rietschel, E. (2003) · Nature reviews. Immunology · doi:10.1038/nri1004 · Cited by 1,392
Cell Type-Specific Involvement of RIG-I in Antiviral Response
Kato, H., Sato, S., Yoneyama, M., Yamamoto, M., Uematsu, S., Matsui, K., Tsujimura, T., Takeda, K., Fujita, T., Takeuchi, O., et al. (2005) · Immunity · doi:10.1016/j.immuni.2005.04.010 · Cited by 1,368
Toll-like Receptor 9–mediated Recognition of Herpes Simplex Virus-2 by Plasmacytoid Dendritic Cells
Lund, J. M., Sato, A., Akira, S., Medzhitov, R. M., & Iwasaki, A. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030162 · Cited by 1,197
Gitlin, L., Barchet, W., Gilfillan, S., Cella, M., Beutler, B., Flavell, R. A., Diamond, M., & Colonna, M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603082103 · Cited by 1,177
Multiple-laboratory comparison of microarray platforms
Irizarry, R. A., Warren, D., Spencer, F., Kim, I. F., Biswal, S., Frank, B. C., Gabrielson, E., Garcia, J. G. N., Geoghegan, J., Germino, G., et al. (2005) · Nature Methods · doi:10.1038/nmeth756 · Cited by 862
Flagged first, then by citations
Cited by
Sorted by citations
Items 201–239 of 239
Tsitoura, E., Kazazi, D., Arslan, D. Ö., Sever, E. A., Khalili, S., Vassilaki, N., Aslanoglou, E., Dérian, N., Six, A., Sezerman, O. U., et al. (2018) · Human Gene Therapy · doi:10.1089/hum.2018.161 · Cited by 2
Ayalew, L. E., Gaba, A., Wang, W., & Tikoo, S. K. (2020) · Springer eBooks · doi:10.1007/978-3-030-51927-8_5 · Cited by 2
siRNA Therapeutic Design: Tools and Challenges
Malefyt, A., Angart, P. A., Chan, C., & Walton, S. P. (2011) · Springer eBooks · doi:10.1007/978-3-642-22517-8_19 · Cited by 2
The gene delivery system for rheumatoid synovium
Nakasato, M., Nonomura, Y., Miyasaka, N., & Kohsaka, H. (2008) · Japanese Journal of Clinical Immunology · doi:10.2177/jsci.31.17 · Cited by 1
Diagnosis and Assessment of Microbial Infections with Host and Microbial microRNA Profiles
Cui, L., Stratton, C. W., & Tang, Y. (2012) · Springer eBooks · doi:10.1007/978-1-4614-3970-7_46 · Cited by 1
Methods to mitigate immune response
Ezeuko, C. C., Efa, B. B., & Matthews, Q. L. (2025) · Elsevier eBooks · doi:10.1016/b978-0-323-89821-8.00005-x · Cited by 1
Human mastadenovirus pneumonia in two immunocompetent patients
Hosch, S., Hamelin, B., Haslbauer, J. D., Field, C. M., Heim, A., Boeck, L., Prince, S. S., Gradistanac, T., Gander, A. E., Keller, P. M., et al. (2025) · Virology Journal · doi:10.1186/s12985-025-02823-6 · Cited by 1
Muscle as a Target for Genetic Vaccine
Zhi, Y., & Gao, G. (2009) · Springer eBooks · doi:10.1007/978-1-4419-1207-7_14 · Cited by 1
Adenovirus-Based Vaccines for the Treatment of Substance Use Disorders
Havlicek, D. F., Rosenberg, J. B., Sondhi, D., Crystal, R. G., & Kaminsky, S. M. (2015) · Springer eBooks · doi:10.1007/978-3-319-23150-1_13 · Cited by 1
Review on Adeno Virus; As a Vaccine Vehicle
Tadesse, B. (2017) · Open Access Journal of Veterinary Science & Research · doi:10.23880/oajvsr-16000138 · Cited by 1
Diagnosis and Assessment of Microbial Infections with Host and Microbial MicroRNA Profiles
Cui, L., Markou, A. N., Stratton, C. W., & Lianidou, E. S. (2018) · Springer eBooks · doi:10.1007/978-3-319-95111-9_23 · Cited by 1
Translating Sleeping Beauty transposition into cellular therapies: Victories and challenges
Izsvák, Z., Hackett, P. B., Cooper, L. J. N., & Ivics, Z. (2011) · BioEssays · doi:10.1002/bies.201190025 · Cited by 1
Gene Silencing Methods Using Vector‐Encoded siRNAs or miRNAs
Liu, Y. P., & Berkhout, B. (2014) · Wiley eBooks · doi:10.1002/9783527647064.ch55 · Cited by 1
Targeted delivery of anti-cancer drugs by MS2 virus-like particles
Yan, R. (2015) · White Rose eTheses Online (University of Leeds, The University of Sheffield, University of York) · Cited by 1
Recombinant adenovirus causes prolonged mobilization of macrophages in the anterior chamber of micePreprint
Meyer, K. J., Pellack, D. R., Hedberg‐Buenz, A., Pomernackas, N., Soukup, D. A., Wang, K., Fingert, J. H., & Anderson, M. G. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.01.13.426423 · Cited by 1
Nokisalmi, P. (2013) · Työväentutkimus Vuosikirja
Recombinant Adenoviruses for Vaccination
Paolo, N. C. D., Shayakhmetov, D. M., & Lieber, A. (2012) · doi:10.1002/9781118345313.ch15
Adenovirus-based gene therapy approaches for hemophilia B
Zhang, W. (2012) · Electronic Theses of LMU Munich (Ludwig-Maximilians-Universität München) · doi:10.5282/edoc.14566
Li, W., Liu, L., Zhu, W., Wang, D., & Zeng, Y. (2013) · Micro & Nano Letters · doi:10.1049/mnl.2012.0384
PDGF Gene Therapy to Accelerate Dental Implant Osseointegration
Jin, Q. (2009) · Deep Blue (University of Michigan)
Replication-competent adenovirus 11p vector as a new oncolytic agent
Silver, J. (2011) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
Towards therapeutic gene delivery to human cancer cells : targeting and entry of baculovirus
Mäkelä, A. R. (2008) · Jyväskylä University Digital Archive (University of Jyväskylä)
Gene- and Viral-Based Therapies for Gliomas
Asadi-Moghaddam, K., & Chiocca, E. A. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4160-5316-3.00109-x
Improving adenovirus-based immunotherapies for treatment of solid tumors
Siurala, M. (2017) · Työväentutkimus Vuosikirja
A Novel Role for Tid1 in HIF2α Regulation
Burnett, D. (2010) · TSpace (University of Toronto)
Dual role of matrix metalloproteinases-2 in thoracic aortic aneurysm
Lee, J. W. (2014) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r3rr1pv80
Transposon Based Gene Therapy as a Treatment for Cancer
Stauber, J. (2015) · Touro Scholar (Touro College)
Katzman, C., Israely, T., Melamed, S., Politi, B., Sittner, A., Yahalom-Ronen, Y., Weiss, S., Rass, R. A., Zamostiano, R., Bacharach, E., et al. (2021) · Viruses · doi:10.3390/v14010011
Gene Transfer Into the Inner Ear
Oestreicher, D. (2019) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-7690
Review on Adeno Virus; As a Vaccine Vehicle
(2017) · ARC Journal of Animal and Veterinary Sciences · doi:10.20431/2455-2518.0302003
The Rationale Behind the Effectiveness of COVID-19 Vaccines and Associated Immunological Mechanisms
Khatib, S. E. (2022) · Turkish Journal of Immunology · doi:10.4274/tji.galenos.2022.55264
Induced Pluripotency: Current Reprogramming Methods and Areas for Improved Therapeutic CapabilitiesPreprint
Lu, B., & Horowitz, N. B. (2023) · doi:10.14293/pr2199.000455.v1
Torres, K. E., & Pollock, R. E. (2010) · Springer eBooks · doi:10.1007/978-1-4419-6102-0_14
Sharma, R. R., Sharma, R., Dua, K., Gupta, G., Chellappan, D. K., Singh, S. K., Singh, T., & Negi, P. (2026) · Pathology - Research and Practice · doi:10.1016/j.prp.2026.156351 · Cited by 1
Xin, P., Chen, Z., Zhang, Y., Gu, J., Jiang, N., & Chen, L. J. (2026) · Biology and Fertility of Soils · doi:10.1007/s00374-025-01972-8
Yamamoto, H., Tamari, M., Wada, S., Takahashi, H., Yoshida-Komiya, H., Saito, H., Morita, H., Matsumoto, K., & Motomura, K. (2026) · Placenta · doi:10.1016/j.placenta.2026.01.005
One virus—many strategies: type-specific interactions between human adenoviruses and innate immunity
Hanrieder, L., & Schreiner, S. (2026) · Journal of Virology · doi:10.1128/jvi.00204-26
Antoun, E., Liu, G., Jayathilaka, D., Yao, X., Rostron, T., Waugh, C., Clark, K., Sopp, P., Fry, J. W., Xia, T., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.08.18.745226
Lee, W., Lee, J., Lee, S. M., & Kim, E. H. (2026) · Vaccines · doi:10.3390/vaccines14090793
Metadata
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
