A novel, disruptive vaccination technology: Self-adjuvanted RNActive ® vaccines
Open accessAbstract
Nucleotide based vaccines represent an enticing, novel approach to vaccination. We have developed a novel immunization technology, RNActive(®) vaccines, that have two important characteristics: mRNA molecules are used whose protein expression capacity has been enhanced by 4 to 5 orders of magnitude by modifications of the nucleotide sequence with the naturally occurring nucleotides A (adenosine), G (guanosine), C (cytosine), U (uridine) that do not affect the primary amino acid sequence. Second, they are complexed with protamine and thus activate the immune system by involvement of toll-like receptor (TLR) 7. Essentially, this bestows self-adjuvant activity on RNActive(®) vaccines. RNActive(®) vaccines induce strong, balanced immune responses comprising humoral and cellular responses, effector and memory responses as well as activation of important subpopulations of immune cells, such as Th1 and Th2 cells. Pre-germinal center and germinal center B cells were detected in human patients upon vaccination. RNActive(®) vaccines successfully protect against lethal challenges with a variety of different influenza strains in preclinical models. Anti-tumor activity was observed preclinically under therapeutic as well as prophylactic conditions. Initial clinical experiences suggest that the preclinical immunogenicity of RNActive(®) could be successfully translated to humans.
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Vaccines based on mRNA offer multifaceted advantages including flexible antigen design, a cost-effective manufacturing process allowing for parallel production of multiple mRNA vaccines, and rapid manufacturing.
“Vaccines based on mRNA could meet these requirements because they offer multifaceted advantages including flexible antigen design, a cost-effective manufacturing process allowing for parallel production of multiple mRNA vaccines1–5 and rapid manufacturing, which could be of crucial importance during pandemics.6”
From Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines (2017) · cites this paper as [2]
The Introduction describes nucleotide-based vaccines as a simple, inexpensive platform compatible with protein engineering, and the Conclusion describes RNA production as flexible and scalable with modest investment (page numbers unavailable). The paper does not establish parallel production of multiple mRNA vaccines. Rapid manufacturing is attached to a separate citation in the citing sentence, not specifically to this source. (LLM, conf=0.84)
Experimental — accuracy not yet measuredBenefits of mRNA vaccines are the induction of balanced and enduring immunity as demonstrated for anti-tumor and prophylactic vaccination, simple supply, and storage at elevated temperature.
“Benefits are the induction of balanced and enduring immunity as demonstrated for anti-tumor and prophylactic vaccination [14–16], simple supply, and storage at elevated temperature, as reviewed elsewhere [17,18].”
The RNActive® platform designed by CureVac combines the use of co-delivered RNA and protamine (a polycationic peptide) complex as adjuvant, which has been shown to effectively trigger innate immune responses and enhance vaccine immunogenicity.
“A vaccine platform (RNActive®) was designed by CureVac186 combining the use of co-delivered RNA and protamine (a polycationic peptide) complex as adjuvant, which has been shown to effectively trigger innate immune responses and enhance vaccine immunogenicity.186–189”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [188]
Protamine was shown to activate TLR7 and TLR8 pathways, thereby showing potential as a delivery vehicle with adjuvant effect for vaccines or gene therapy.
“In addition, protamine was shown to activate TLR7 and TLR8 pathways, thereby showing potential as a delivery vehicle with adjuvant effect for vaccines or gene therapy.188”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [188]
In a preclinical study, CureVac's RNActive delivery platform activated TLR7 and generated durable immune responses against a lethal influenza dose in 18-month-old mice.
“In a preclinical study, CureVac’s RNActive delivery platform activated TLR7 and generated durable immune responses against a lethal influenza dose in 18-month-old mice105.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [105]
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- Authors
- Kallen, K.-J., Heidenreich, R., Schnee, M., Petsch, B., Schlake, T., Thess, A., Baumhof, P., Scheel, B., Koch, S. D., & Fotin-Mleczek, M.
- Affiliations
- CureVac (Germany) (DE)
- Corresponding author
- Kallen, Karl-Josef
- Venue
- Human Vaccines & Immunotherapeutics
- Publisher
- Informa UK Limited
- Published
- 2013-10-04
- Volume
- 9
- Issue
- 10
- Pages
- 2263-2276
- ISSN
- 2164-5515 (ISSN-L)
- 2164-554X
- PMC
- PMC3906413
- OpenAlex
- W1995580450
- Cited by
- 223
- References
- 36
- Citations by year
- 2026: 11 · 2025: 19 · 2024: 17 · 2023: 31 · 2022: 34 · 2021: 30 · 2020: 16 · 2019: 14 · 2018: 11 · 2017: 8 · 2016: 10 · 2015: 6 · 2014: 13 · 2013: 3
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Human Vaccines & Immunotherapeutics (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- 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 Response and Inflammation
- Keywords
- mRNA vaccines, protamine, humoral and cellular immune response, Th1/Th2 balance, germinal center B cells, influenza vaccination, anticancer activity, immunogenicity
- MeSH terms
- Humans, RNA, Vaccination, Viral Vaccines, Cancer Vaccines, Toll-Like Receptor 7
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