# Frédéric Martinon
**Frédéric Martinon** is the researcher credited in the Nobel Assembly's background to the 2023 [Nobel Prize in Physiology or Medicine](https://www.edgepedia.org/nobel-prize-in-physiology-or-medicine) for having "demonstrated the induction of antigen-specific cytotoxic T lymphocyte responses in mice injected with liposome-formulated mRNA encoding the influenza virus nucleoprotein"[1](https://www.nobelprize.org/prizes/medicine/2023/advanced-information/). He was first author of the 1993 European Journal of Immunology paper that reported this result, published under the name **Frédéric Martinon**[2](https://onlinelibrary.wiley.com/doi/10.1002/eji.1830230749) • [3](https://www.nature.com/articles/s41565-023-01347-w). That paper was the first use of in vitro-transcribed mRNA as a vaccine, and it is the earliest demonstration that a synthetic mRNA, delivered in a particle, can prime a cellular immune response in a living animal[1](https://www.nobelprize.org/prizes/medicine/2023/advanced-information/).
| Key fact | Detail |
|---|---|
| Paper | Martinon, F., et al., "Induction of virus-specific cytotoxic T lymphocytes in vivo by liposome-entrapped mRNA", Eur J Immunol, 1993, 23(7), pp. 1719–1722; DOI 10.1002/eji.1830230749; PMID 8325342[1](https://www.nobelprize.org/prizes/medicine/2023/advanced-information/) • [4](https://europepmc.org/article/MED/8325342) |
| Authors and institutions | Frédéric Martinon, Sivadasan Krishnan, Gerlinde Lenzen, Rémy Magné, Elisabeth Gomard, Jean-Gérard Guillet, Jean-Paul Lévy, and Pierre Meulien; INSERM U152 (Marcy L'Etoile), Pasteur Mérieux Sérums et Vaccins, and Transgène S.A.[2](https://onlinelibrary.wiley.com/doi/10.1002/eji.1830230749) |
| Antigen and delivery | In vitro-transcribed mRNA encoding influenza A/NT nucleoprotein, encapsulated in cholesterol:dipalmitoylphosphatidylcholine:phosphatidylserine (5:4:1) liposomes extruded through 200 nm membranes[4](https://europepmc.org/article/MED/8325342) • [5](https://www.ovid.com/journals/ejoi/fulltext/10.1002/eji.202249941~nonreplicating-synthetic-mrna-vaccines-a-journey-through-the) |
| Result | Virus-specific CTLs induced in mice by intravenous or subcutaneous injection (not intraperitoneal), lysing both peptide-sensitized and virus-infected targets, across three MHC haplotypes[6](https://www.academia.edu/22640364/Induction_of_virus_specific_cytotoxic_T_lymphocytesin_vivo_by_liposome_entrapped_mRNA) |
| Encapsulation requirement | mRNA alone, or mRNA mixed with preformed vesicles, failed to raise CTL; the mRNA had to be encapsulated[6](https://www.academia.edu/22640364/Induction_of_virus_specific_cytotoxic_T_lymphocytesin_vivo_by_liposome_entrapped_mRNA) |
| Standing | Cited as reference 4 in the Nobel Assembly's 2023 advanced information; 353 citations recorded by the publisher[1](https://www.nobelprize.org/prizes/medicine/2023/advanced-information/) • [2](https://onlinelibrary.wiley.com/doi/10.1002/eji.1830230749) |
## The 1993 experiment
The paper appeared on 1 July 1993 as a Short Paper in volume 23, issue 7 of the European Journal of Immunology, pages 1719–1722[4](https://europepmc.org/article/MED/8325342) • [2](https://onlinelibrary.wiley.com/doi/10.1002/eji.1830230749). Martinon was affiliated with INSERM U152 at Marcy L'Etoile, France; the work was a collaboration between that INSERM unit, the vaccine company Pasteur Mérieux Sérums et Vaccins (where corresponding author Pierre Meulien was based), and Transgène S.A., supported by a grant from the Agence Nationale de Recherche sur le SIDA[2](https://onlinelibrary.wiley.com/doi/10.1002/eji.1830230749). A historical review in the same journal describes the team as that of Pierre Meulien at Pasteur Mérieux together with the Institut Cochin Research Centre and INSERM[5](https://www.ovid.com/journals/ejoi/fulltext/10.1002/eji.202249941~nonreplicating-synthetic-mrna-vaccines-a-journey-through-the).
The immunogen was nucleoprotein (NP) mRNA of influenza A/NT, produced by in vitro transcription and encapsulated in simple cholesterol/phosphatidylcholine/phosphatidylserine liposomes made by the detergent removal technique[4](https://europepmc.org/article/MED/8325342). The historical review gives the formulation as a 5:4:1 cholesterol:dipalmitoylphosphatidylcholine:phosphatidylserine mixture dialyzed with the mRNA and extruded through 200 nm pore membranes[5](https://www.ovid.com/journals/ejoi/fulltext/10.1002/eji.202249941~nonreplicating-synthetic-mrna-vaccines-a-journey-through-the).
Three findings carried the paper. First, *encapsulation was necessary*: injection of mRNA alone, or mRNA mixed with preformed vesicles, failed to raise CTL, so the liposome was doing more than carrying the RNA[6](https://www.academia.edu/22640364/Induction_of_virus_specific_cytotoxic_T_lymphocytesin_vivo_by_liposome_entrapped_mRNA). Second, the route mattered: subcutaneous and intravenous injection with a three-week prime-boost interval induced CTLs that killed virus-infected target cells in vitro, while intraperitoneal injection did not, a dependence the authors could not fully explain[6](https://www.academia.edu/22640364/Induction_of_virus_specific_cytotoxic_T_lymphocytesin_vivo_by_liposome_entrapped_mRNA) • [5](https://www.ovid.com/journals/ejoi/fulltext/10.1002/eji.202249941~nonreplicating-synthetic-mrna-vaccines-a-journey-through-the). Third, the response was broad: the CTLs lysed both peptide-sensitized and virus-infected targets, and the same mRNA-liposome preparation elicited virus-specific CTLs in mice of three different MHC haplotypes; the immunized animals were BALB/c mice, and CTL activity was measured by lysis of P815 and EL4 target cells[6](https://www.academia.edu/22640364/Induction_of_virus_specific_cytotoxic_T_lymphocytesin_vivo_by_liposome_entrapped_mRNA). A note added in proof records that Ulmer et al. had just reported in Science (1993;259:1745) that a DNA construct encoding NP induced CTL and protection against influenza challenge, placing the mRNA result alongside the first DNA-vaccination result within weeks of each other[6](https://www.academia.edu/22640364/Induction_of_virus_specific_cytotoxic_T_lymphocytesin_vivo_by_liposome_entrapped_mRNA).
## Scientific context and comparison with other early milestones
The 1993 study sat third in a short sequence. In 1990, mRNA-mediated gene transfer was first validated in vivo, with functional reporter-protein expression after direct injection of naked mRNA into mouse muscle; the Nobel background attributes this to [Philip Felgner](https://www.edgepedia.org/philip-l-felgner) and colleagues, while Nature's 2021 history and Karikó's lecture cite it as Wolff, J. A. et al., Science 247, 1465–1468 (1990), an attribution difference that remains unresolved[7](https://www.nobelprizemedicine.org/wp-content/uploads/2023/10/Scientific_background_2023-1.pdf) • [8](https://www.nature.com/articles/d41586-021-02483-w). In 1992, intrahypothalamic injection of vasopressin mRNA temporarily reversed diabetes insipidus in rats[9](https://pubs.rsc.org/en/content/articlehtml/2025/pm/d4pm00309h). Then came 1993: Martinon and colleagues formulated mRNA with liposomes and elicited anti-influenza cytotoxic T lymphocytes[9](https://pubs.rsc.org/en/content/articlehtml/2025/pm/d4pm00309h).
The milestone was the immune response, not expression. Wolff's 1990 work showed mRNA could make protein in vivo; Martinon's showed it could *prime a cellular immune response*, the hard problem for a vaccine, since cytotoxic T lymphocytes recognize antigen presented on MHC molecules rather than free protein. A specialist review calls this the demonstration that synthetic mRNA could be used to vaccinate[5](https://www.ovid.com/journals/ejoi/fulltext/10.1002/eji.202249941~nonreplicating-synthetic-mrna-vaccines-a-journey-through-the), and a three-decade retrospective names Martinon et al. as pioneers showing that liposomes containing mRNA encoding influenza nucleoprotein elicited virus-specific CTLs[10](https://backoffice.biblio.ugent.be/download/8628303/8628317).
Successors followed quickly. In 1995, Robert Conry and colleagues developed a cancer antigen-encoding mRNA vaccine, and Conry et al. demonstrated that a prophylactic mRNA vaccine encoding carcinoembryonic antigen induced anti-tumoral antibody responses, the humoral counterpart to Martinon's cellular result[3](https://www.nature.com/articles/s41565-023-01347-w) • [10](https://backoffice.biblio.ugent.be/download/8628303/8628317).
The field then thinned. Karikó's Nobel lecture explains that most early teams left because in vitro-transcribed mRNA was not potent and not stable, producing only small amounts of protein for a very short period[11](https://www.nobelprize.org/uploads/2026/09/kariko-lecture.pdf).
## Recognition in the 2023 Nobel Prize
The 2023 prize to [Katalin Karikó](https://www.edgepedia.org/katalin-kariko) and [Drew Weissman](https://www.edgepedia.org/drew-weissman) concerned nucleoside base modifications that enabled effective mRNA vaccines against COVID-19, and the Committee's scientific background places Martinon immediately after the 1990 muscle-expression study: "Soon thereafter, Martinon et al. demonstrated the induction of antigen-specific cytotoxic T lymphocyte responses in mice injected with liposome-formulated mRNA encoding the influenza virus nucleoprotein"[7](https://www.nobelprizemedicine.org/wp-content/uploads/2023/10/Scientific_background_2023-1.pdf). The advanced information cites the paper as reference 4 in its reference list[1](https://www.nobelprize.org/prizes/medicine/2023/advanced-information/). Karikó's own lecture states plainly that "the first application of IVT mRNA as a vaccine was developed against nucleoprotein of the influenza virus by Martinon and colleagues and was tested in mice"[11](https://www.nobelprize.org/uploads/2026/09/kariko-lecture.pdf). The Committee's framing also notes that during the 1990s only a small community of investigators continued to explore mRNA as a vaccine platform[1](https://www.nobelprize.org/prizes/medicine/2023/advanced-information/).
## Reception and afterlife of the 1993 result
Retrospective genealogies have kept it in the canon: Nature's 2021 history of mRNA vaccines lists Martinon et al., Eur. J. Immunol. 23, 1719–1722 (1993), immediately after Wolff et al. 1990 among the key early milestones[8](https://www.nature.com/articles/d41586-021-02483-w); a 2023 open-access review of mRNA vaccines and delivery systems cites it among the foundational early studies[12](https://pmc.ncbi.nlm.nih.gov/articles/PMC10405914/); and Nature Reviews Materials in 2017 flagged it as one of the earliest studies using liposome-entrapped mRNA for immunization[13](https://web.archive.org/web/20220426004604/https://www.nature.com/articles/natrevmats201756). Since the mRNA vaccine era, attention has grown: Nature Nanotechnology's 2023 review states that although mRNA vaccines as nanomedicines seem new, the concept dates to 1993, when Frédéric Martinon first developed mRNA-nanoparticle delivery systems encoding an influenza virus nucleoprotein[3](https://www.nature.com/articles/s41565-023-01347-w), and a 2025 RSC Pharmaceutics review reiterates the milestone in its timeline[9](https://pubs.rsc.org/en/content/articlehtml/2025/pm/d4pm00309h).
## References
1. [The Nobel Prize in Physiology or Medicine 2023 – Advanced information, Nobel Assembly](https://www.nobelprize.org/prizes/medicine/2023/advanced-information/)
2. [Martinon, F., et al. (1993). Induction of virus-specific cytotoxic T lymphocytes in vivo by liposome-entrapped mRNA. European Journal of Immunology 23(7):1719–1722, Wiley Online Library](https://onlinelibrary.wiley.com/doi/10.1002/eji.1830230749)
3. [mRNA therapy at the convergence of genetics and nanomedicine, Nature Nanotechnology (2023)](https://www.nature.com/articles/s41565-023-01347-w)
4. [Induction of virus-specific cytotoxic T lymphocytes in vivo by liposome-entrapped mRNA, Europe PMC record (PMID 8325342)](https://europepmc.org/article/MED/8325342)
5. [Nonreplicating synthetic mRNA vaccines: A journey through the European (Journal of Immunology) history](https://www.ovid.com/journals/ejoi/fulltext/10.1002/eji.202249941~nonreplicating-synthetic-mrna-vaccines-a-journey-through-the)
6. [Full-text copy of Martinon et al. 1993, Academia.edu](https://www.academia.edu/22640364/Induction_of_virus_specific_cytotoxic_T_lymphocytesin_vivo_by_liposome_entrapped_mRNA)
7. [Scientific background: Nobel Prize in Physiology or Medicine 2023 (PDF)](https://www.nobelprizemedicine.org/wp-content/uploads/2023/10/Scientific_background_2023-1.pdf)
8. [The tangled history of mRNA vaccines, Nature (2021)](https://www.nature.com/articles/d41586-021-02483-w)
9. [The rise of mRNA therapeutic vaccines, RSC Pharmaceutics (2025)](https://pubs.rsc.org/en/content/articlehtml/2025/pm/d4pm00309h)
10. [Three decades of messenger RNA vaccine development (institutional repository copy)](https://backoffice.biblio.ugent.be/download/8628303/8628317)
11. [Katalin Karikó Nobel lecture: Developing mRNA for therapy (PDF)](https://www.nobelprize.org/uploads/2026/09/kariko-lecture.pdf)
12. [Recent Advances in Messenger RNA (mRNA) Vaccines and Their Delivery Systems: A Review, PMC (2023)](https://pmc.ncbi.nlm.nih.gov/articles/PMC10405914/)
13. [Tools for translation: non-viral materials for therapeutic mRNA delivery, Nature Reviews Materials (2017), archived copy](https://web.archive.org/web/20220426004604/https://www.nature.com/articles/natrevmats201756)
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*Topic: Encyclopedia › Life and health › Life and health scientists › Medical and health researchers › Immunology and allergy researchers › Cellular and molecular immunology researchers › Lymphocyte and antibody researchers › Surnames A to L*
*Initially written Oct 10, 2026 · Edited: Oct 11, 2026; Oct 15, 2026*
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License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license