A thermostable messenger RNA based vaccine against rabies
Open accessAbstract
Although effective rabies virus vaccines have been existing for decades, each year, rabies virus infections still cause around 50.000 fatalities worldwide.Most of these cases occur in developing countries, where these vaccines are not available.The reasons for this are the prohibitive high costs of cell culture or egg grown rabies virus vaccines and the lack of a functional cold chain in many regions in which rabies virus is endemic.Here, we describe the excellent temperature resistance of a non-replicating mRNA based rabies virus vaccine encoding the rabies virus glycoprotein (RABV-G).Prolonged storage of the vaccine from -80˚C to up to +70˚C for several months did not impact the protective capacity of the mRNA vaccine.Efficacy after storage was demonstrated by the induction of rabies specific virus neutralizing antibodies and protection in mice against lethal rabies infection.Moreover, storing the vaccine at oscillating temperatures between +4˚and +56˚C for 20 cycles in order to simulate interruptions of the cold chain during vaccine transport, did not affect the vaccine's immunogenicity and protective characteristics, indicating that maintenance of a cold chain is not essential for this vaccine. Author summaryConventional prophylactic vaccines require transport and storage under controlled temperatures in an unbroken cold chain.Therefore, distribution of many vaccines is restricted to areas where the cold chain can be maintained which excludes especially rural areas in many countries from continues vaccine supply.Unfortunately, some diseases that can be prevented by vaccination, like the rabies virus infection, are still endemic in such areas.Therefore, logistic reasons often prevent delivery of life saving vaccines to areas in which they are most needed.Here, we describe an mRNA vaccine encoding the rabies virus glycoprotein (RABV-G) that remains protective in a mouse challenge model upon storage at highly variable temperatures.These results suggest that such a vaccine allows storage outside the cold chain and can therefore reach all areas of the world where rabies
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Both CVnCoV and CV2CoV are based on RNActive technology and consist of non-chemically modified sequence-engineered mRNA without pseudouridine.
“Both CVnCoV and CV2CoV are based on RNActive technology4–7 and consist of non-chemically modified sequence-engineered mRNA without pseudouridine6–12.”
From Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine (2022) · cites this paper as [9]
The Introduction and Methods describe a rabies vaccine based on RNActive technology, including optimization of its mRNA sequence. They do not identify CVnCoV or CV2CoV or establish that either uses this technology. The passages also do not say whether their mRNA is chemically unmodified or lacks pseudouridine. (LLM, conf=0.87)
Experimental — accuracy not yet measuredFreeze-drying for mRNA vaccine conservation was shown to effectively reduce storage requirements and is considered a promising technique to improve mRNA vaccine stability.
“A more recent storage approach involves employing freeze-drying to mRNA vaccine conservation, which was shown to effectively reduce storage requirements, being thus considered a promising technique to improve mRNA vaccine stability.472,473”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [472]
In preclinical studies, CureVac's sequence-optimized RABV-G vaccine against rabies could withstand exposure to temperatures ranging from −80 °C to +70 °C for several months.
“In preclinical studies, CureVac demonstrated that its sequence-optimized RABV-G vaccine against rabies could withstand exposure to temperatures ranging from −80 °C to +70 °C for several months243.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [243]
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Nano/microparticle Formulations for Universal Influenza Vaccines
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- Authors
- Stitz, L., Vogel, A., Schnee, M., Voss, D., Rauch, S., Mutzke, T., Ketterer, T., Kramps, T., & Petsch, B.
- Affiliations
- Friedrich-Loeffler-Institut (DE)
- CureVac (Germany) (DE)
- Corresponding author
- Petsch, Benjamin
- Venue
- PLOS Neglected Tropical Diseases
- Publisher
- Public Library of Science (PLoS)
- Published
- 2017-12-07
- Volume
- 11
- Issue
- 12
- Pages
- e0006108
- ISSN
- 1935-2727 (ISSN-L)
- 1935-2735
- PMC
- PMC5737050
- OpenAlex
- W2772901255
- Cited by
- 117
- References
- 18
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 12 · 2023: 19 · 2022: 26 · 2021: 22 · 2020: 14 · 2019: 5 · 2018: 4 · 2016: 1
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Update notices
- new_version (2017-12-19)
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS neglected tropical diseases (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- OpenAgrar (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Bundesministerium für Bildung und Forschung (02PK2178)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › Rabies epidemiology and control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- rabies virus, mRNA vaccines, rabies virus glycoprotein, thermostable vaccine, cold chain, vaccine storage, vaccine transport, virus-neutralizing antibodies, non-replicating vaccine, rabies prevention
- MeSH terms
- Immunogenicity, Vaccine, Animals, Antibodies, Viral, Antigens, Viral, Glycoproteins, Rabies, Rabies Vaccines, Rabies virus, RNA, Messenger, Temperature, Vaccines, Synthetic, Viral Envelope Proteins, Mice, Antibodies, Neutralizing, Vaccine Potency
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