Induction of virus‐specific cytotoxic T lymphocytes in vivo by liposome‐entrapped mRNA
Abstract
The induction of anti-influenza cytotoxic T lymphocytes (CTL) in vivo by immunizing mice with liposomes containing messenger RNA (mRNA) encoding the influenza virus nucleoprotein (NP) is described. NP mRNA, obtained by in vitro transcription, was encapsulated into simple cholesterol/phosphatidylcholine/phosphatidylserine liposomes by the detergent removal technique. The dependence of the route of mRNA-liposomes delivery on CTL induction was studied. The CTL induced were identical to those obtained in vivo with infectious virus in terms of specificity, lysing both peptide-sensitized and virus-infected targets. Furthermore, with the same mRNA-liposome preparation, virus-specific CTL responses could be also elicited in mice of three different haplotypes each of them known to present a distinct NP peptide in an MHC-restricted fashion. The relevance of these results in the context of vaccine development is discussed.
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mRNA vaccines have been formulated with synthetic delivery vehicles such as liposomes and cationic polymers to increase potency.
“Hence, mRNA vaccines have been formulated with synthetic delivery vehicles such as liposomes (16) and cationic polymers (17) to increase potency.”
From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [16]
It was not until 1993 that mRNA was used as a vaccine for the first time to elicit a specific immune response against the encoded pathogenic antigen in a preclinical setting using lipid-based delivery.
“It was not until 1993 that mRNA was used as a vaccine for the first time to elicit a specific immune response against the encoded pathogenic antigen in a preclinical setting using lipid-based delivery.22”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [22]
The first mRNA vaccine was made of liposomes and mRNA encoding an influenza virus nucleoprotein.
“The first mRNA vaccine was made of liposomes and mRNA encoding an influenza virus nucleoprotein184.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [184]
The first mRNA vaccine, designed in 1993, was able to induce virus-specific cytotoxic T cell responses in mice.
“This vaccine, designed in 1993, was able to induce virus-specific cytotoxic T cell responses in mice184.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [184]
Lipid nanoparticle-mRNA vaccines are being investigated as influenza vaccines, with some formulations in clinical trials.
“Lipid nanoparticle–mRNA vaccines are also being investigated as influenza vaccines29,41,156,157,159,184,189–191, with some formulations in clinical trials (Table 1).”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [184]
Martinon et al. showed that liposomes containing mRNA encoding the influenza virus nucleoprotein elicited virus-specific cytotoxic T lymphocytes.
“As pioneers, Martinon et al. showed that liposomes containing mRNA encoding the influenza virus nucleoprotein elicited virus-specific cytotoxic T lymphocytes (CTLs) [3].”
From Three decades of messenger RNA vaccine development (2019) · cites this paper as [3]
Encapsulation of RNA in lipid carriers and their utility in vaccination was demonstrated.
“encapsulation of RNA in lipid carriers 72 , and their utility in vaccination 73 , was demonstrated.”
From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [73]
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- Authors
- Martinon, F., Krishnan, S., Lenzen, G., Magné, R., Gomard, E., Guillet, J., Lévy, J., & Meulien, P.
- Affiliations
- Inserm (FR)
- Institut Cochin (FR)
- Corresponding author
- Meulien, Pierre
- ORCID
- Martinon, Frédéric
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 1993-07
- Volume
- 23
- Issue
- 7
- Pages
- 1719-1722
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- OpenAlex
- W2083958143
- Cited by
- 473
- References
- 28
- Citations by year
- 2026: 18 · 2025: 42 · 2024: 51 · 2023: 59 · 2022: 58 · 2021: 64 · 2020: 18 · 2019: 10 · 2018: 12 · 2017: 8 · 2016: 12 · 2015: 13 · 2014: 12 · 2013: 9 · 2012: 10
- FWCI
- 2.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- cytotoxic T lymphocytes, influenza virus, nucleocapsid protein, mRNA vaccines, MHC restriction, peptide presentation, vaccine development, in vitro transcription
- MeSH terms
- Animals, Antigens, Viral, Cytotoxicity, Immunologic, Immunity, Cellular, Liposomes, Mice, Inbred Strains, Nucleoproteins, Influenza A virus, RNA, Messenger, T-Lymphocytes, Cytotoxic, Vaccines, Synthetic, Viral Core Proteins, Viral Vaccines, Nucleocapsid Proteins, Mice
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