Optimised non-coding regions of mRNA SARS-CoV-2 vaccine CV2CoV improves homogeneous and heterogenous neutralising antibody responses
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Abstract
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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SciScore for 10.1101/2021.05.13.443734: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable Animals: Female and male rats (Wistar, 7-8 weeks of age) were provided and handled by Preclinics Gesellschaft für präklinische Forschung mbH, (Potsdam, Germany). Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Specific S protein expression was assessed via staining with Human anti SARS CoV S antibody (CR3022) (Creative Biolabs, Cat. anti SARS CoV Ssuggested: NoneCR3022suggested: NoneMRO-1214LC) followed by goat anti-human IgG F(ab’)2 fragment PE antibody (Immuno Research, Cat. 109-116-097) in a BD FACS Canto II cell analyzer and the FlowJo 10 … SciScore for 10.1101/2021.05.13.443734: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable Animals: Female and male rats (Wistar, 7-8 weeks of age) were provided and handled by Preclinics Gesellschaft für präklinische Forschung mbH, (Potsdam, Germany). Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Specific S protein expression was assessed via staining with Human anti SARS CoV S antibody (CR3022) (Creative Biolabs, Cat. anti SARS CoV Ssuggested: NoneCR3022suggested: NoneMRO-1214LC) followed by goat anti-human IgG F(ab’)2 fragment PE antibody (Immuno Research, Cat. 109-116-097) in a BD FACS Canto II cell analyzer and the FlowJo 10 software. anti-human IgGsuggested: (Jackson ImmunoResearch Labs Cat# 109-116-097, RRID:AB_2337677)Antibody analysis: SARS-CoV-2 Spike RBD protein specific IgG1 and IgG2a binding antibodies were detected via ELISA. SARS-CoV-2 Spike RBD protein specific IgG1suggested: NoneExperimental Models: Cell Lines Sentences Resources In vitro protein expression: For detection of mRNA expression in cell culture, HeLa cells were seeded in 6-well plates at a density of 400.000 cells/well. 24h later, cells were transfected with 2μg of mRNA per well via Lipofection. HeLasuggested: NoneLastly, 100 μl of trypsinated VeroE6 cells (cells of one confluent TC175 flask per 100 ml) in DMEM with 2 % penicillin/streptomycin supplementation was added to each well. VeroE6suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)Experimental Models: Organisms/Strains Sentences Resources Animals: Female and male rats (Wistar, 7-8 weeks of age) were provided and handled by Preclinics Gesellschaft für präklinische Forschung mbH, (Potsdam, Germany). Wistarsuggested: NoneSoftware and Algorithms Sentences Resources MRO-1214LC) followed by goat anti-human IgG F(ab’)2 fragment PE antibody (Immuno Research, Cat. 109-116-097) in a BD FACS Canto II cell analyzer and the FlowJo 10 software. FlowJosuggested: (FlowJo, RRID:SCR_008520)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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