Optimised Non-Coding Regions of mRNA SARS-CoV-2 Vaccine CV2CoV Improves Homologous and Heterologous 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 the CV2CoV mRNA than with the CVnCoV mRNA. Vaccination with CV2CoV also induced higher titres of virus neutralising antibodies with accelerated kinetics in rats compared with CVnCoV. Significant cross-neutralisation 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 were 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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
CV2CoV induces high neutralizing antibodies in rats and non-human primates, with titers comparable to those seen with Comirnaty.
“CV2CoV has now entered clinical testing (NCT05260437) and has been shown to induce high neutralizing antibodies in rats10 and non-human primates11, with titers comparable to those seen with Comirnaty, a licensed mRNA COVID-19 vaccine.”
From Efficacy of an unmodified bivalent mRNA vaccine against SARS-CoV-2 variants in female small animal models (2023) · cites this paper as [10]
Results §3.3 reports high neutralising-antibody titres in CV2CoV-vaccinated rats. The Discussion §4 mentions non-human-primate findings from a prior study, but this paper does not report a comparison of CV2CoV titres with Comirnaty; its direct comparator is CVnCoV. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe optimised non-coding regions of mRNA SARS-CoV-2 vaccine CV2CoV improve homologous and heterologous neutralising antibody responses in rats and non-human primates, compared with CVnCoV and other modified mRNA vaccines.
“The optimised non-coding regions of mRNA SARS-CoV-2 vaccine CV2CoV have previously been shown to improve homologous and heterologous neutralising antibody responses in rats and non-human primates, compared with CVnCoV and other modified mRNA vaccines10,11.”
From Efficacy of an unmodified bivalent mRNA vaccine against SARS-CoV-2 variants in female small animal models (2023) · cites this paper as [10]
The Abstract and Discussion (page numbers unavailable) report stronger homologous and variant cross-neutralising responses with CV2CoV than with CVnCoV in rats. The Discussion also reports consistent findings from a non-human-primate study. This paper does not establish that CV2CoV outperformed other modified mRNA vaccines. (LLM, conf=0.87)
Experimental — accuracy not yet measuredRat-derived data translated very well to improved immunogenicity and protective efficacy in a non-human primate challenge model for SARS-CoV-2.
“The rat-derived data translated very well to improved immunogenicity and protective efficacy in a non-human primate challenge model for SARS-CoV-210,11 and our cross-neutralization results emphasize the broad antigen coverage induced by the bivalent vaccine.”
From Efficacy of an unmodified bivalent mRNA vaccine against SARS-CoV-2 variants in female small animal models (2023) · cites this paper as [10]
The mRNA CV2CoV vaccine does not include chemically modified nucleosides.
“does not include chemically modified nucleosides, as previously described10.”
From Efficacy of an unmodified bivalent mRNA vaccine against SARS-CoV-2 variants in female small animal models (2023) · cites this paper as [10]
Previous studies did not unveil variability between sexes.
“Previous studies did not unveil variability between sexes10 and manipulation of female animals reduces the biosafety risks in BSL3 during challenge infection.”
From Efficacy of an unmodified bivalent mRNA vaccine against SARS-CoV-2 variants in female small animal models (2023) · cites this paper as [10]
Materials and Methods §2.3 says the study used female and male rats, but does not compare outcomes by sex. Results §3.2 reports no body-weight difference between vaccine groups, not between sexes. Searches for sex differences and male-versus-female antibody responses found no passage establishing the claimed absence of sex variability; page numbers were not available in our copy. (LLM, conf=0.72)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A SIMPLE METHOD OF ESTIMATING FIFTY PER CENT ENDPOINTS12
REED, L. J., & Muench, H. (1938) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a118408 · Cited by 20,341 · see citing works
Detection of a SARS-CoV-2 variant of concern in South Africa
Tegally, H., Wilkinson, E., Giovanetti, M., Iranzadeh, A., Fonseca, V., Giandhari, J., Doolabh, D., Pillay, S., San, E. J., Msomi, N., et al. (2021) · Nature · doi:10.1038/s41586-021-03402-9 · Cited by 2,510 · see citing works
Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization
Planas, D., Veyer, D., Baidaliuk, A., Staropoli, I., Guivel-Benhassine, F., Rajah, M. M., Planchais, C., Porrot, F., Robillard, N., Puech, J., et al. (2021) · Nature · doi:10.1038/s41586-021-03777-9 · Cited by 1,992 · see citing works
Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity
Garcia-Beltran, W. F., Lam, E. C., St. Denis, K., Nitido, A. D., Garcia, Z. H., Hauser, B. M., Feldman, J., Pavlovic, M. N., Gregory, D. J., Poznansky, M. C., et al. (2021) · Cell · doi:10.1016/j.cell.2021.03.013 · Cited by 1,353 · see citing works
Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant
Madhi, S. A., Baillie, V., Cutland, C. L., Voysey, M., Koen, A. L., Fairlie, L., Padayachee, S. D., Dheda, K., Barnabas, S. L., Bhorat, Q. E., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2102214 · Cited by 1,257 · see citing works
SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma
Wibmer, C. K., Ayres, F., Hermanus, T., Madzivhandila, M., Kgagudi, P., Oosthuysen, B., Lambson, B. E., de Oliveira, T., Vermeulen, M., van der Berg, K., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01285-x · Cited by 1,147 · see citing works
Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen
Pallesen, J., Wang, N., Corbett, K. S., Wrapp, D., Kirchdoerfer, R. N., Turner, H. L., Cottrell, C. A., Becker, M. M., Wang, L., Shi, W., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1707304114 · Cited by 1,073 · see citing works
Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera
Zhou, D., Dejnirattisai, W., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H. M. E., Tuekprakhon, A., Nutalai, R., et al. (2021) · Cell · doi:10.1016/j.cell.2021.02.037 · Cited by 992 · see citing works
SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies
Hoffmann, M., Arora, P., Groß, R., Seidel, A., Hörnich, B. F., Hahn, A. S., Krüger, N., Graichen, L., Hofmann-Winkler, H., Kempf, A., et al. (2021) · Cell · doi:10.1016/j.cell.2021.03.036 · Cited by 897 · see citing works
Antibody evasion by the P.1 strain of SARS-CoV-2
Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H. M. E., Tuekprakhon, A., Nutalai, R., et al. (2021) · Cell · doi:10.1016/j.cell.2021.03.055 · Cited by 583 · see citing works
New Vaccine Technologies to Combat Outbreak Situations
Rauch, S., Jasny, E., Schmidt, K. E., & Petsch, B. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01963 · Cited by 579 · see citing works
Self-citationNeutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine–elicited human sera
Muik, A., Wallisch, A.-K., Sänger, B., Swanson, K. A., Mühl, J., Chen, W., Cai, H., Maurus, D., Sarkar, R., Türeci, Ö., et al. (2021) · Science · doi:10.1126/science.abg6105 · Cited by 515 · see citing works
Kirchdoerfer, R. N., Wang, N., Pallesen, J., Wrapp, D., Turner, H. L., Cottrell, C. A., Corbett, K. S., Graham, B. S., McLellan, J. S., & Ward, A. B. (2018) · Scientific Reports · doi:10.1038/s41598-018-34171-7 · Cited by 466 · see citing works
Wu, K., Werner, A. P., Moliva, J. I., Koch, M., Choi, A., Stewart-Jones, G. B. E., Bennett, H., Boyoglu-Barnum, S., Shi, W., Graham, B. S., et al. (2021) · doi:10.1101/2021.01.25.427948 · Cited by 419 · see citing works
Fotin-Mleczek, M., Duchardt, K. M., Lorenz, C., Pfeiffer, R., Ojkić-Zrna, S., Probst, J., & Kallen, K.-J. (2011) · Journal of Immunotherapy · doi:10.1097/cji.0b013e3181f7dbe8 · Cited by 335 · cited 1× · see citing works
“mRNA Vaccines Both CVnCoV and CV2CoV mRNAs, produced using the RNActive® platform, have a 5′ cap1 structure, GC-enriched open reading frame (ORF), 3′ UTR, a polyA stretch, and chemically unmodified nucleosides [14].”
MethodKübler, H., Scheel, B., Gnad-Vogt, U., Miller, K., Schultze-Seemann, W., vom Dorp, F., Parmiani, G., Hampel, C., Wedel, S., Trojan, L., et al. (2015) · Journal for Immunotherapy of Cancer · doi:10.1186/s40425-015-0068-y · Cited by 287 · see citing works
Zeng, B., Gao, L., Zhou, Q., Yu, K., & Sun, F. (2022) · BMC Medicine · doi:10.1186/s12916-022-02397-y · Cited by 267 · see citing works
Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines
Lutz, J., Lazzaro, S., Habbeddine, M., Schmidt, K. E., Baumhof, P., Mui, B. L., Tam, Y. K., Madden, T. D., Hope, M. J., Heidenreich, R., et al. (2017) · npj Vaccines · doi:10.1038/s41541-017-0032-6 · Cited by 257 · see citing works
Aldrich, C., Leroux–Roels, I., Huang, K. B., Bica, M. A., Loeliger, E., Schoenborn-Kellenberger, O., Walz, L., Leroux-Roels, G., von Sonnenburg, F., & Oostvogels, L. (2021) · Vaccine · doi:10.1016/j.vaccine.2020.12.070 · Cited by 204 · see citing works
Rauch, S., Roth, N., Schwendt, K., Fotin-Mleczek, M., Mueller, S. O., & Petsch, B. (2021) · npj Vaccines · doi:10.1038/s41541-021-00311-w · Cited by 165 · see citing works
Self-citationAu, W. Y., & Cheung, P. P.-H. (2022) · BMJ · doi:10.1136/bmj-2022-069989 · Cited by 143 · see citing works
Neutralization of SARS-CoV-2 Variants by mRNA and Adenoviral Vector Vaccine-Elicited Antibodies
Tada, T., Zhou, H., Samanovic, M. I., Dcosta, B. M., Cornelius, A. R., Herati, R. S., Mulligan, M. J., & Landau, N. R. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.797589 · Cited by 131 · see citing works
Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine
Gebre, M. S., Rauch, S., Roth, N., Yu, J., Chandrashekar, A., Mercado, N. B., He, X., Liu, J., McMahan, K., Martinot, A., et al. (2022) · Nature · doi:10.1038/s41586-021-04231-6 · Cited by 127 · see citing works
Self-citationA thermostable messenger RNA based vaccine against rabies
Stitz, L., Vogel, A., Schnee, M., Voss, D., Rauch, S., Mutzke, T., Ketterer, T., Kramps, T., & Petsch, B. (2017) · PLOS Neglected Tropical Diseases · doi:10.1371/journal.pntd.0006108 · Cited by 117 · see citing works
Self-citationFotin‐Mleczek, M., Zanzinger, K., Heidenreich, R., Lorenz, C., Thess, A., Duchardt, K. M., & Kallen, K. (2012) · The Journal of Gene Medicine · doi:10.1002/jgm.2605 · Cited by 103 · see citing works
Tada, T., Zhou, H., Samanovic, M., et al. (2021) · bioRxiv · doi:10.1101/2021.07.19.452771 · Cited by 97 · see citing works
Structures of Omicron spike complexes and implications for neutralizing antibody development
Guo, H., Gao, Y., Li, T., Li, T., Lu, Y., Zheng, L., Liu, Y., Yang, T., Luo, F., Song, S., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110770 · Cited by 59 · see citing works
mRNA vaccine CVnCoV protects non-human primates from SARS-CoV-2 challenge infection
Rauch, S., Gooch, K., Hall, Y., Salguero, F. J., Dennis, M. J., Gleeson, F. V., Harris, D., Ho, C., Humphries, H. E., Longet, S., et al. (2020) · doi:10.1101/2020.12.23.424138 · Cited by 48 · see citing works
Self-citationCheng, H., Peng, Z., Si, S., Alifu, X., Zhou, H., Chi, P., Zhuang, Y., Mo, M., & Yu, Y. (2022) · Vaccines · doi:10.3390/vaccines10050798 · Cited by 44 · see citing works
Lassaunière, R., Fonager, J., Rasmussen, M., Frische, A., Polacek, C., Rasmussen, T. B., Lohse, L., Belsham, G. J., Underwood, A. P., Winckelmann, A. A., et al. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.698944 · Cited by 43 · see citing works
Hoerr, I. (2000) · doi:10.1002/1521-4141(200001)30:1
Flagged first, then by citations
Cited by
Sorted by citations
The Storage and In-Use Stability of mRNA Vaccines and Therapeutics: Not A Cold Case
Blenke, E. O., Örnskov, E., Schöneich, C., Nilsson, G. Å., Volkin, D. B., Mastrobattista, E., Almarsson, Ö., & Crommelin, D. J. A. (2022) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2022.11.001 · Cited by 214 · see citing works
Revolutionizing immunization: a comprehensive review of mRNA vaccine technology and applications
Leong, K. Y., Tham, S. K., & Poh, C. L. (2025) · Virology Journal · doi:10.1186/s12985-025-02645-6 · Cited by 128 · see citing works
mRNA-based VP8* nanoparticle vaccines against rotavirus are highly immunogenic in rodents
Roier, S., Prasad, V. M., McNeal, M., Lee, K. K., Petsch, B., & Rauch, S. (2023) · npj Vaccines · doi:10.1038/s41541-023-00790-z · Cited by 32 · see citing works
Self-citationFrom Immunogen to COVID-19 vaccines: Prospects for the post-pandemic era
Miao, G., Chen, Z., Cao, H., Wu, W., Chu, X., Liu, H., Zhang, L., Zhu, H., Cai, H., Lu, X., et al. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.114208 · Cited by 26 · see citing works
Recent Advancements in mRNA Vaccines: From Target Selection to Delivery Systems
Wu, Z., Sun, W., & Qi, H. (2024) · Vaccines · doi:10.3390/vaccines12080873 · Cited by 25 · see citing works
Corleis, B., Hoffmann, D., Rauch, S., Fricke, C., Roth, N., Gergen, J., Kovacikova, K., Schlottau, K., Halwe, N. J., Ulrich, L., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36110-1 · Cited by 22 · see citing works
Self-citationInnate sensing of mRNA vaccines
Wuebben, C., Bartok, E., & Hartmann, G. (2022) · Current Opinion in Immunology · doi:10.1016/j.coi.2022.102249 · Cited by 16 · see citing works
Hensley, C., Roier, S., Zhou, P., Schnur, S., Nyblade, C., Parreño, V. G., Frazier, A., Frazier, M., Kiley, K., O’Brien, S., et al. (2024) · Vaccines · doi:10.3390/vaccines12030260 · Cited by 14 · see citing works
Self-citationThe Bright Future of mRNA as a Therapeutic Molecule
Vélez, D. E., Torres, B. L., & Hernández, G. (2025) · Genes · doi:10.3390/genes16040376 · Cited by 10 · see citing works
Roth, N., Gergen, J., Kovacikova, K., Mueller, S. O., Ulrich, L., Schön, J., Halwe, N. J., Fricke, C., Corleis, B., Dorhoi, A., et al. (2023) · Vaccines · doi:10.3390/vaccines11020318 · Cited by 10 · see citing works
Self-citationPreclinical development of an mRNA-based multiepitope immunotherapeutic for glioblastoma
Lutz, J., Feist, R. K., Sonntag, T., Peguero-Sánchez, E., Wolter, K., Bick, R., Bauer, J., Walz, J. S., & Heidenreich, R. (2025) · Cancer Immunology, Immunotherapy · doi:10.1007/s00262-025-04178-x · Cited by 9 · see citing works
From Sequence to System: Enhancing IVT mRNA Vaccine Effectiveness through Cutting-Edge Technologies
Xu, L., Li, C., Liao, R., Xiao, Q., Wang, X., Zhao, Z., Zhang, W., Ding, X., Cao, Y., Cai, L., et al. (2024) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.4c00863 · Cited by 10 · see citing works
Pre-clinical models to define correlates of protection for SARS-CoV-2
Brady, C., Tipton, T., Longet, S., & Carroll, M. W. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1166664 · Cited by 6 · see citing works
Leroux‐Roels, I., Coster, I. D., Borobia, A. M., Langley, J. M., Mazarro, D. O., Ruíz‐Antorán, B., Berrè, S., Germain, S., Knauer, C., Koch, S., et al. (2026) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2026.2631804 · Cited by 5 · see citing works
Boulch, M. L., Jacquet, E., Nhiri, N., Shmulevitz, M., & Jais, P. H. (2024) · Scientific Reports · doi:10.1038/s41598-024-55947-0 · Cited by 4 · see citing works
Introduction to RNA Vaccines Post COVID-19
Kramps, T. (2024) · Methods in molecular biology · doi:10.1007/978-1-0716-3770-8_1 · Cited by 4 · see citing works
Omange, R. W., Varco-Merth, B. D., Fadeyi, O., Marenco, A., Takata, H., Duell, D. M., Goodwin, W. D., Armitage, P., Fennessey, C. M., Köse, E., et al. (2026) · Journal of Clinical Investigation · doi:10.1172/jci198294 · Cited by 2 · see citing works
Self-citationKrueger, J., Ruotsalainen, J. J., Lutz, J., & Heidenreich, R. (2026) · Scientific Reports · doi:10.1038/s41598-026-65120-4 · Cited by 1 · see citing works
mRNA vaccine-induced IgG mediates nasal SARS-CoV-2 clearance in mice
Fricke, C., Ulrich, L., Kochmann, J., Gergen, J., Kovacikova, K., Roth, N., Beer, J., Schnepf, D., Mettenleiter, T. C., Rauch, S., et al. (2024) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2024.102360 · Cited by 1 · see citing works
Self-citationModified or Unmodified mRNA Vaccines? – The Biochemistry of Pseudouridine and mRNA Pseudouridylation
Morais, P., & Yu, Y. (2024) · Wiley eBooks · doi:10.1002/9783527838394.ch3 · Cited by 2 · see citing works
Krog, T. F., Haukland, I. S., & Haugland, G. T. (2026) · Vaccines · doi:10.3390/vaccines14050367
Draycheva, A., Millecam, J., & Caba, E. (2026) · International Journal of Toxicology · doi:10.1177/10915818261446630
- 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
- Vaccines
- Publisher
- MDPI AG
- Published
- 2022-08-04
- Volume
- 10
- Issue
- 8
- Pages
- 1251
- ISSN
- 2076-393X (ISSN-L)
- PMC
- PMC9414064
- OpenAlex
- W4289861418
- Cited by
- 22
- References
- 28
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 7 · 2023: 5 · 2022: 2
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Vaccines (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- OpenAgrar (submittedVersion, cc-by)
- Funders
- German Federal Ministry of Education and Research (01KI20703)
- core funds of the German Federal Ministry of Food and Agriculture (01KI20703)
- CureVac AG (01KI20703)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- SARS-CoV-2, mRNA vaccines, non-coding regions, virus neutralising antibodies, cross-neutralization, SARS-CoV-2 variants, Alpha variant, Beta variant, dose sparing, vaccine immunogenicity, rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
