Optimization of Non-Coding Regions Improves Protective Efficacy of an mRNA SARS-CoV-2 Vaccine in Nonhuman Primates
Open accessAbstract
The CVnCoV (CureVac) mRNA vaccine for SARS-CoV-2 has recently been evaluated in a phase 2b/3 efficacy trial in humans. CV2CoV is a second-generation mRNA vaccine with optimized non-coding regions and enhanced antigen expression. Here we report a head-to-head study of the immunogenicity and protective efficacy of CVnCoV and CV2CoV in nonhuman primates. We immunized 18 cynomolgus macaques with two doses of 12 ug of lipid nanoparticle formulated CVnCoV, CV2CoV, or sham (N=6/group). CV2CoV induced substantially higher binding and neutralizing antibodies, memory B cell responses, and T cell responses as compared with CVnCoV. CV2CoV also induced more potent neutralizing antibody responses against SARS-CoV-2 variants, including B.1.351 (beta), B.1.617.2 (delta), and C.37 (lambda). While CVnCoV provided partial protection against SARS-CoV-2 challenge, CV2CoV afforded robust protection with markedly lower viral loads in the upper and lower respiratory tract. Antibody responses correlated with protective efficacy. These data demonstrate that optimization of non-coding regions can greatly improve the immunogenicity and protective efficacy of an mRNA SARS-CoV-2 vaccine in nonhuman primates.
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Phase I clinical data showed CVnCoV has acceptable tolerance and high immunogenicity.
“Phase I clinical data showed that CVnCoV has acceptable tolerance and high immunogenicity.29,427”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [427]
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References 41 · Cited by 8
Research works printed but not linked: 1
- Nicole Roth, J.S., Donata Hoffmann, Moritz Thran, Andreas Thess, Stefan O. Mueller, Benjamin Petsch and Susanne Rauch, CV2CoV, an enhanced mRNA-based SARS-CoV-2 vaccine candidate, supports higher protein expression and improved immunogenicity in rats. bioRxiv, 2021.
- Authors
- Gebre, M. S., Rauch, S., Roth, N., Yu, J., Chandrashekar, A., Mercado, N. B., He, X., Liu, J., McMahan, K., Martinot, A., Giffin, T., Hope, D., Patel, S., Sellers, D., Sanborn, O., Barrett, J., Liu, X., Cole, A. C., Pessaint, L., Valentin, D., Flinchbaugh, Z., Yalley-Ogunro, J., Muench, J., Brown, R., Cook, A., Teow, E., Andersen, H., Lewis, M. G., Mueller, S. O., Petsch, B., & Barouch, D. H.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- CureVac (Germany) (DE)
- Tufts University (US)
- Bioqual (US)
- Corresponding author
- Rauch, Susanne
- Barouch, Dan H.
- ORCID
- Gebre, Makda S.
- Rauch, Susanne
- Yu, Jingyou
- Chandrashekar, Abishek
- Mercado, Noe B.
- He, Xuan
- Liu, Jinyan
- McMahan, Katherine
- Martinot, Amanda
- Hope, David
- Patel, Shivani
- Sellers, Daniel
- Barrett, Julia
- Liu, Xiaowen
- Cole, Andrew C.
- Pessaint, Laurent
- Muench, Jeanne
- Brown, Renita
- Cook, Anthony
- Lewis, Mark G.
- Mueller, Stefan O.
- Petsch, Benjamin
- Barouch, Dan H.
- Venue
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2021-08-16
- OpenAlex
- W3195246271
- Cited by
- 8
- References
- 41
- Citations by year
- 2023: 2 · 2022: 3 · 2021: 3
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nd
- Locations
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- Funders
- Bundesministerium für Bildung und Forschung (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, lipid nanoparticles, immunogenicity, neutralizing antibodies, memory B cells, T cell response, SARS-CoV-2 variants, Beta variant, Delta variant, viral load, respiratory tract, non-human primates, cynomolgus macaques, vaccine efficacy
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