Design of SARS-CoV-2 RBD mRNA Vaccine Using Novel Ionizable Lipids
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Abstract
The novel coronavirus SARS-CoV-2 has been identified as the causal agent of COVID-19 and stands at the center of the current global human pandemic, with death toll exceeding one million. The urgent need for a vaccine has led to the development of various immunization approaches. mRNA vaccines represent a cell-free, simple and rapid platform for immunization, and therefore have been employed in recent studies towards the development of a SARS-CoV-2 vaccine. In this study, we present the design of a lipid nanoparticles (LNP)-encapsulated receptor binding domain (RBD) mRNA vaccine. Several ionizable lipids have been evaluated in vivo in a luciferase mRNA reporter assay, and two leading LNPs formulation have been chosen for the subsequent RBD mRNA vaccine experiment. Intramuscular administration of LNP RBD mRNA elicited robust humoral response, high level of neutralizing antibodies and a Th1-biased cellular response in BALB/c mice. These novel lipids open new avenues for mRNA vaccines in general and for a COVID19 vaccine in particular.
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SciScore for 10.1101/2020.10.15.341537: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: All animal experiments were conducted in accordance with the guideline of the Israel Institute for Biological Research (IIBR) animal experiments committee. Randomization Animals: Female BALB/c mice (6–8 weeks old) were obtained from Charles River and randomly assigned into cages in groups of 10 animals. Blinding not detected. Power Analysis not detected. Sex as a biological variable Animals: Female BALB/c mice (6–8 weeks old) were obtained from Charles River and randomly assigned into cages in groups of 10 animals. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources For plaque reduction neutralization test … SciScore for 10.1101/2020.10.15.341537: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: All animal experiments were conducted in accordance with the guideline of the Israel Institute for Biological Research (IIBR) animal experiments committee. Randomization Animals: Female BALB/c mice (6–8 weeks old) were obtained from Charles River and randomly assigned into cages in groups of 10 animals. Blinding not detected. Power Analysis not detected. Sex as a biological variable Animals: Female BALB/c mice (6–8 weeks old) were obtained from Charles River and randomly assigned into cages in groups of 10 animals. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources For plaque reduction neutralization test (PRNT), Vero E6 cells (0.5*106 cells/well in 12-well plates) were cultured in DMEM supplemented with 10% FCS, MEM non-essential amino acids, 2nM L-Glutamine, 100 Units/ml Penicillin, 0.1 mg/ml streptomycin and 12.5 Units/ml Nystatin (Biological Industries, Israel) overnight at 37°C, 5% CO2. Vero E6suggested: RRID:CVCL_XD71)Experimental Models: Organisms/Strains Sentences Resources Animals: Female BALB/c mice (6–8 weeks old) were obtained from Charles River and randomly assigned into cages in groups of 10 animals. BALB/csuggested: NoneSoftware and Algorithms Sentences Resources The purified protein was sterile-filtered and stored in PBS. mRNA: CleanCap® firefly luciferase mRNA was a kind gift from BioNtech RNA Pharmaceuticals (Mainz, Germany). BioNtechsuggested: NoneAll statistical analyses were performed using GraphPad Prism 8 statistical software. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on page 8. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
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.
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