Cited by 121RNA Interference and Gene DeliveryImmunotherapy and Immune ResponsesNanoparticle-Based Drug Delivery

Particle-mediated intravenous delivery of antigen mRNA results in strong antigen-specific T-cell responses despite the induction of type I interferon

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Broos, Katrijn, Van der Jeught, Kevin, Puttemans, Janik, Goyvaerts, Cleo, Heirman, Carlo, Dewitte, Heleen, Verbeke, Rein, Lentacker, Ine +2 more·2016·Molecular Therapy — Nucleic Acids

Abstract

Cancer vaccines based on mRNA are extensively studied. The fragile nature of mRNA has instigated research into carriers that can protect it from ribonucleases and as such enable its systemic use. However, carrier-mediated delivery of mRNA has been linked to production of type I interferon (IFN) that was reported to compromise the effectiveness of mRNA vaccines. In this study, we evaluated a cationic lipid for encapsulation of mRNA. The nanometer-sized, negatively charged lipid mRNA particles (LMPs) efficiently transfected dendritic cells and macrophages in vitro. Furthermore, i.v. delivery of LMPs resulted in rapid expression of the mRNA-encoded protein in spleen and liver, predominantly in CD11c(+) cells and to a minor extent in CD11b(+) cells. Intravenous immunization of mice with LMPs containing ovalbumin, human papilloma virus E7, and tyrosinase-related protein-2 mRNA, either combined or separately, elicited strong antigen-specific T-cell responses. We further showed the production of type I IFNs upon i.v. LMP delivery. Although this decreased the expression of the mRNA-encoded protein, it supported the induction of antigen-specific T-cell responses. These data question the current notion that type I IFNs hamper particle-mediated mRNA vaccines.

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Crossref · 10.1038/mtna.2016.38

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  • Several research groups underlined that the type I interferon response can act as a driving force for mRNA vaccines to elicit cytotoxic T cell responses.

    “several research groups underlined that the type I IFN response can act as a driving force for mRNA vaccines to elicit cytotoxic T cell responses [1,60,61]”

    From The dawn of mRNA vaccines: the COVID-19 case (2021) · cites this paper as [61]

  • i.v. administration of mRNA vaccines has been shown to induce stronger antigen-specific cytotoxic T cell responses compared with local injection.

    “For example, i.v. administration of mRNA vaccines has been shown to induce stronger antigen-specific cytotoxic T cell responses compared with local injection26,148,149.”

    From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [149]

  • In cancer immunotherapy, it is essential to evoke a systemic immune response to obtain antitumor immunity, making i.v. delivery appealing for mRNA-based cancer vaccines.

    “In the specific case of cancer immunotherapy, it was proven essential to evoke a systemic immune response to obtain antitumor immunity, which makes i.v.delivery a highly appealing administration route for mRNA-based cancer vaccines [92,136,137].”

    From Three decades of messenger RNA vaccine development (2019) · cites this paper as [136]

  • Two papers showed that intravenous administration of unmodified mRNA lipid nanoparticles triggered a rapid and systemic induction of type I IFNs, involving selective targeting of dendritic cells and macrophages and activation of the TLR7 pathway.

    “Two papers showed that the i.v.administration of unmodified mRNA LNPs triggered a rapid and systemic induction of type I IFNs, which involved the selective targeting of DCs and macrophages and the activation of the TLR7 pathway[92,136].”

    From Three decades of messenger RNA vaccine development (2019) · cites this paper as [136]

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Research works printed but not linked: 1

  1. Van Lint, S, Heirman, C, Thielemans, K and Breckpot, K (2013). mRNA: from a chemical blueprint for protein production to an off-the-shelf therapeutic. Hum Vaccin Immunother 9: 265–274. 23291946 PMC3859745

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Authors
Broos, K., Van der Jeught, K., Puttemans, J., Goyvaerts, C., Heirman, C., Dewitte, H., Verbeke, R., Lentacker, I., Thielemans, K., & Breckpot, K.
Affiliations
  • Vrije Universiteit Brussel (BE)
  • Ghent University (BE)
Corresponding author
Breckpot, Karine
Venue
Molecular Therapy — Nucleic Acids
Publisher
Elsevier BV
Published
2016
Volume
5
Issue
6
Pages
e326
ISSN
2162-2531 (ISSN-L)
OpenAlex
W2466602492
Cited by
121
References
68
Citations by year
2026: 4 · 2025: 15 · 2024: 20 · 2023: 14 · 2022: 14 · 2021: 16 · 2020: 8 · 2019: 9 · 2018: 8 · 2017: 9 · 2016: 4
FWCI
5.20
Type
journal article
Language
en
Open access
Locations
  • Molecular Therapy — Nucleic Acids (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • VUBIR (Vrije Universiteit Brussel) (submittedVersion)
Funders
  • Bundesministerium für Gesundheit
  • Fonds Wetenschappelijk Onderzoek
  • Vlaamse Liga Tegen Kanker
  • Vlaamse regering
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
mRNA vaccines, intravenous delivery, type I interferon, antigen-specific T cell responses, dendritic cells, macrophages, ovalbumin, E7 oncoprotein, tyrosinase-related protein 2, cancer vaccines

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