Optimised non-coding regions of mRNA SARS-CoV-2 vaccine CV2CoV improves homogeneous and heterogenous neutralising antibody responses
Open accessAbstract
More than two years after the emergence of SARS-CoV-2, 33 COVID-19 vaccines, based on different platforms, have been approved in 197 countries. Novel variants that are less efficiently neutralised by antibodies raised against ancestral SARS-CoV-2 are circulating, highlighting the need to adapt vaccination strategies. Here, we compare the immunogenicity of a first-generation mRNA vaccine candidate, CVnCoV, with a second-generation mRNA vaccine candidate, CV2CoV, in rats. Higher levels of spike (S) protein expression were observed in cell culture with CV2CoV mRNA than with CVnCoV mRNA. Vaccination with CV2CoV also induced higher titres of virus neutralising antibodies with accelerated kinetics in rats compared with CVnCoV. Significant cross-neutralization of the SARS-CoV-2 variants, Alpha (B.1.1.7), Beta (B.1.351), and the ‘mink’ variant (B1.1.298) that were circulating at the time in early 2021 was also demonstrated. In addition, CV2CoV induced higher levels of antibodies at lower doses than CVnCoV, suggesting that dose-sparing could be possible with the next generation SARS-CoV-2 vaccine which could improve worldwide vaccine supply.
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CV2CoV is a second-generation mRNA vaccine containing non-modified nucleosides but with optimized non-coding regions and enhanced antigen expression.
“CV2CoV is a second-generation mRNA vaccine containing non-modified nucleosides but with optimized non-coding regions and enhanced antigen expression.”
From Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine (2022) · cites this paper as [3]
CV2CoV has previously been shown to lead to higher antigen expression than CVnCoV in cell culture.
“CV2CoV has previously been shown to lead to higher antigen expression than CVnCoV in cell culture3.”
From Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine (2022) · cites this paper as [3]
CV2CoV has different non-coding regions flanking the open reading frame, which have previously been shown to improve transgene expression and protection against SARS-CoV-2 in ACE2-transgenic mice.
“CV2CoV has been engineered with different non-coding regions flanking the open reading frame, which have previously been shown to improve transgene expression3 and protection against SARS-CoV-2 in ACE2-transgenic mice2.”
From Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine (2022) · cites this paper as [3]
The citation to this paper is attached to the claim of protection against SARS-CoV-2 in ACE2-transgenic mice. Sections 2.3–2.4 describe experiments in Wistar rats, and the Introduction mentions protective efficacy in non-human primates; no passage found reports protection in ACE2-transgenic mice. The paper does describe different non-coding regions and increased protein expression, but those are not the protection claim attached to this citation. (LLM, conf=0.76)
Experimental — accuracy not yet measuredCureVac further engineered the UTRs of the mRNA and showed a superior immunological profile in preclinical tests.
“However, CureVac further engineered the UTRs of the mRNA and showed a superior immunological profile in preclinical tests,136,137”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [137]
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- Authors
- Roth, N., Schön, J., Hoffmann, D., Thran, M., Thess, A., Mueller, S. O., Petsch, B., & Rauch, S.
- Affiliations
- CureVac (Germany) (DE)
- Friedrich-Loeffler-Institut (DE)
- Corresponding author
- Petsch, Benjamin
- Venue
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2021-05-13
- OpenAlex
- W3162846174
- Cited by
- 18
- References
- 40
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1 · 2022: 7 · 2021: 7
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Locations
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Funders
- Bundesministerium für Bildung und Forschung (01KI20703, SARS-CoV-2)
- Bundesministerium für Ernährung und Landwirtschaft
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- SARS-CoV-2, mRNA vaccines, neutralizing antibodies, cross-neutralization, SARS-CoV-2 variants, Alpha variant, Beta variant, dose sparing, vaccine immunogenicity, rats
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