The Opposing Effect of Type I IFN on the T Cell Response by Non-modified mRNA-Lipoplex Vaccines Is Determined by the Route of Administration
Open accessAbstract
mRNA-lipoplex vaccines are currently being explored in phase II clinical trials for the treatment of patients with advanced solid tumors. Mechanistically, these mRNA-lipoplex vaccines are characterized by the induction of type I interferon (IFN) centered innate responses. Earlier studies have identified type I IFNs as major regulators of the T cell response instigated by mRNA-lipoplex vaccines. However, stimulatory or, in contrast, profound inhibitory effects of type I IFNs were described depending on the study. In this mouse study, we demonstrated that the opposing roles of type I IFN signaling on the magnitude of the vaccine-evoked T cell responses is dependent on the route of mRNA-lipoplex administration and is regulated at the level of the T cells rather than indirectly through modulation of dendritic cell function. This study helps to understand the double-edged sword character of type I IFN induction upon mRNA-based vaccine treatment and may contribute to a more rational design of mRNA vaccination regimens.
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The type I IFN activity of mRNA vaccines can prematurely stop mRNA translation, thereby reducing antigen availability and diminishing the vaccine's efficacy to obtain adaptive immune responses.
“the type I IFN activity of mRNA vaccines can prematurely stop mRNA-translation, thereby reducing antigen availability and diminishing the vaccine's efficacy to obtain adaptive immune responses [63,64]”
From The dawn of mRNA vaccines: the COVID-19 case (2021) · cites this paper as [64]
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The dawn of mRNA vaccines: the COVID-19 case
Verbeke, R., Lentacker, I., De Smedt, S. C., & Dewitte, H. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.03.043 · Cited by 504 · see citing works
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- Authors
- Van Hoecke, L., Roose, K., Ballegeer, M., Zhong, Z., Sanders, N. N., De Koker, S., Saelens, X., & Van Lint, S.
- Affiliations
- Ghent University (BE)
- Venue
- Molecular Therapy Nucleic Acids
- Publisher
- Elsevier BV
- Published
- 2020-12
- Volume
- 22
- Pages
- 373-381
- ISSN
- 2162-2531 (ISSN-L)
- PMC
- PMC7533292
- OpenAlex
- W3085627131
- Cited by
- 55
- References
- 7
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 8 · 2023: 8 · 2022: 11 · 2021: 11
- FWCI
- 2.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Therapy — Nucleic Acids (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Horizon 2020 Framework Programme (648124)
- European Research Council
- Universiteit Gent (BOF2015/GOA/031)
- China Scholarship Council (201607650018)
- Medizinischen Hochschule Hannover
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- type I interferon, T cell response, route of administration, mRNA vaccines, cancer immunotherapy, innate immune response, dendritic cells, solid tumors, vaccine design
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