Type I interferon inhibits antibody responses induced by a chimpanzee adenovirus vector.
Open accessAbstract
Recent studies have indicated that type I interferon (IFN) enhances antibody responses and promotes isotype switching. In this study, we analyzed the role of type I IFN signaling during the generation of transgene product-specific antibody responses elicited by recombinant adenovirus (Ad) vectors. A vector derived from a human Ad serotype (AdHu5) induced low levels of type I IFN following infection of dendritic cells (DCs) and stimulated normal transgene product-specific antibody responses in mice that have a defective type I IFN receptor (IFNAR(-/-)). A vector derived from a chimpanzee Ad serotype (AdC68) induced very high levels of type I IFN following infection of DCs, and surprisingly, primed stronger transgene product-specific antibody responses in IFNAR(-/-) mice compared to wild-type mice. The increased antibody response in IFNAR(-/-) mice vaccinated with the AdC68 vector was mainly due to the generation of IgG1 antibodies that were not elicited in wild-type mice. The induction of IgG1 antibodies correlated with an increase in transgene product expression in IFNAR(-/-) mice and was not associated with an increase in T helper 2 responses. We conclude that type I IFN, when induced at high levels, can downregulate transgene product expression of Ad vectors and inhibit the formation of optimal antibody responses.
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BNT162b2, mRNA-1273, and ChAdOx1 nCoV-19 have been shown to induce type I interferon.
“Both BNT162b2 and mRNA-1273, as well as the adenoviral-vectored vaccine ChAdOx1 nCoV-19, have been shown to induce type I interferon, thus potentially inducing pathogen-agnostic protection75–77.”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [76]
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References 46 · Cited by 78
- Authors
- Hensley, S. E., Cun, A. S., Giles-Davis, W., Li, Y., Xiang, Z., Lasaro, M. O., Williams, B. R. G., Silverman, R. H., & Ertl, H. C. J.
- Affiliations
- The Wistar Institute (US)
- Cleveland Clinic (US)
- Corresponding author
- Ertl, Hildegund C J
- ORCID
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2007-02
- Volume
- 15
- Issue
- 2
- Pages
- 393-403
- ISSN
- 1525-0016 (ISSN-L)
- OpenAlex
- W2012445117
- Cited by
- 78
- References
- 46
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 8 · 2022: 4 · 2021: 10 · 2020: 5 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 5 · 2012: 2
- FWCI
- 2.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania
- National Institutes of Health (5r01ai037166-09)
- National Institute of Allergy and Infectious Diseases (5R01AI037166-09, P01AI052271)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007748, DK007748-09)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- type I interferon, antibody response, recombinant adenovirus vector, IFNAR-deficient mice, dendritic cells, IgG1 antibodies, class switch recombination, transgene expression, T helper 2 response, vaccine immunogenicity
- MeSH terms
- Adenoviridae, Animals, Bone Marrow Cells, Pan troglodytes, Dendritic Cells, Enzyme-Linked Immunosorbent Assay, Genetic Vectors, Humans, Immunoglobulin G, Interferon Type I, Mice, Inbred C57BL, Signal Transduction, Cytokines, Mice, Knockout, Th2 Cells, Mice, Receptor, Interferon alpha-beta
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