Polarization of immunity induced by direct injection of naked sequence-stabilized mRNA vaccines
Open accessAbstract
In the context of developing a safe genetic vaccination strategy we tested and studied globin-stabilized mRNA-based vaccination in mice. This vaccination strategy has the advantages of genetic vaccination (easy production, adaptability to any disease and inexpensive storage when lyophilized), but not the drawbacks of DNA vaccination (long-term uncontrolled expression of a transgene, possibility of integration into the host genome and possible induction of anti-DNA antibodies). We report here that injection of naked beta-globin untranslated region (UTR)-stabilized mRNA coding for beta-galactosidase is followed by detectable translation in vivo. In addition, we show that such a vaccination strategy primes a T helper 2 (Th2) type of response which can be enhanced and shifted to a Th1-type immune response by application of recombinant granulocyte/macrophage colony-stimulating factor 1 day after mRNA injection. Our data demonstrate that the administration of globin UTR-stabilized mRNA is a versatile vaccination strategy that can be manipulated to fit the requirement of antiviral, antibacterial or antitumor immunity.
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Antigen-encoding RNA has the advantages of a genetic vaccine (delivery of all epitopes of the whole antigen, easy manufacturing, standardized purification) and is a safe pharmaceutical characterized by transient expression and lack of integration into the genome of the treated host.
“Antigen-encoding RNA 1,2 has the advantages of a genetic vaccine (delivery of all epitopes of the whole antigen, easy manufacturing, standardized purification) and the added value of a safe pharmaceutical characterized by transient expression and lack of integration into the genome of the treated host.”
From Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells (2006) · cites this paper as [2]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredThe 5′ UTR is mostly retrieved from genes such as globin, Hsp70, axon dynein heavy chain 2 (DNAH2), and hydroxysteroid dehydrogenase (3β-HSD).
“In contrast, the 5′ UTR is mostly retrieved from genes such as globin, Hsp70, axon dynein heavy chain 2 (DNAH2), and hydroxysteroid dehydrogenase (3β-HSD).144,145”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [144]
Intradermal injections of GM-CSF contributed to infiltration of monocytes and migration of mRNA-transfected, matured dendritic cells to lymph nodes.
“Intradermal injections of granulocyte-macrophage colony-stimulating factor (GM-CSF) contributed to the infiltration of monocytes, and to the migration of mRNA-transfected, matured DCs to the LNs [86,87].”
From Three decades of messenger RNA vaccine development (2019) · cites this paper as [87]
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- Authors
- Carralot, J.-P., Probst, J., Hoerr, I., Scheel, B., Teufel, R., Jung, G., Rammensee, H.-G., & Pascolo, S.
- Affiliations
- CureVac (Germany) (DE)
- University of Tübingen (DE)
- Corresponding author
- Pascolo, S.
- Venue
- Cellular and Molecular Life Sciences CMLS
- Published
- 2004-09
- Volume
- 61
- Issue
- 18
- Pages
- 2418-2424
- ISSN
- 1420-682X (ISSN-L)
- 1420-9071
- PMC
- PMC7079797
- OpenAlex
- W2038715317
- Cited by
- 149
- References
- 26
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 8 · 2023: 11 · 2022: 9 · 2021: 14 · 2020: 5 · 2019: 5 · 2018: 6 · 2017: 3 · 2016: 7 · 2015: 7 · 2014: 7 · 2013: 8 · 2012: 5
- FWCI
- 2.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cellular and Molecular Life Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- mRNA vaccines, beta-galactosidase, genetic immunization, T helper 2 response, Th1 polarization, GM-CSF, in vivo translation, immunogenicity
- MeSH terms
- Animals, Antigens, beta-Galactosidase, Cell Line, Female, Globins, Injections, Mice, Inbred BALB C, RNA, Messenger, Protein Biosynthesis, Vaccines, Granulocyte-Macrophage Colony-Stimulating Factor, Cytokines, Th1 Cells, Th2 Cells, Mice
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