Induction of neutralizing antibodies against SARS-CoV-2 variants by a multivalent mRNA-lipid nanoparticle vaccine encoding SARS-CoV-2/SARS-CoV Spike protein receptor-binding domains
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Abstract
To address the need for multivalent vaccines against Coronaviridae that can be rapidly developed and manufactured, we compared antibody responses against SARS-CoV, SARS-CoV-2, and several variants of concern in mice immunized with mRNA-lipid nanoparticle vaccines encoding homodimers or heterodimers of SARS-CoV/SARS-CoV-2 receptor-binding domains. All vaccine constructs induced robust anti-viral antibody responses, and the heterodimeric vaccine elicited an IgG response capable of cross-neutralizing SARS-CoV, SARS-CoV-2 Wuhan-Hu-1, B.1.351 (beta), and B.1.617.2 (delta) variants.
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SciScore for 10.1101/2022.04.28.489834: (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 Immunization of mice with RBD mRNA-LNPs: Male C57BL/6J mice (aged 4–5 weeks) were purchased from the Jackson Laboratory and housed according to the regulatory standards of the University of California, San Diego. Randomization Mice were randomly allocated to experimental groups. Blinding not detected. Power Analysis not detected. Cell Line Authentication Contamination: The cell lines were tested and confirmed to be negative for mycoplasma. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Cell lines: HEK293FT and Vero E6 cells were maintained in Dulbecco’s Modified Eagle’s Medium containing 10% fetal bovine serum (GIBCO). HEK293FTsuggested: NoneSciScore for 10.1101/2022.04.28.489834: (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 Immunization of mice with RBD mRNA-LNPs: Male C57BL/6J mice (aged 4–5 weeks) were purchased from the Jackson Laboratory and housed according to the regulatory standards of the University of California, San Diego. Randomization Mice were randomly allocated to experimental groups. Blinding not detected. Power Analysis not detected. Cell Line Authentication Contamination: The cell lines were tested and confirmed to be negative for mycoplasma. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Cell lines: HEK293FT and Vero E6 cells were maintained in Dulbecco’s Modified Eagle’s Medium containing 10% fetal bovine serum (GIBCO). HEK293FTsuggested: NoneVero E6suggested: NoneSARS-CoV-2 pseudovirus production: Plasmids encoding the Spike proteins (lacking the C-terminal 19-amino acids) of SARS-CoV-1 (CUHK-W1), SARS-CoV-2 (Wuhan-Hu-1), variant B.1.351, variant B.1.617.2, Wuhan-N501Y, and Wuhan-E484K were transfected into 293T cells with Lipofectamine 3000 (ThermoFisher). 293Tsuggested: NoneVerification of protein-coding capability of vaccine mRNAs: To confirm that the synthesized mRNAs could be translated into GFP or RBD proteins, 293FT cells were seeded at 3 × 105 cells/mL in 6-well plates, grown for 24 h, and then transfected with 1 mg mRNA per well using Lipofectamine 3000 (Invitrogen) according to the manufacturer’s instructions. 293FTsuggested: NoneVero cells were seeded at 2 × 105 cells/mL of 100 μL/well in 96-well plates and cultured overnight at 37°C. Verosuggested: NoneExperimental Models: Organisms/Strains Sentences Resources Immunization of mice with RBD mRNA-LNPs: Male C57BL/6J mice (aged 4–5 weeks) were purchased from the Jackson Laboratory and housed according to the regulatory standards of the University of California, San Diego. C57BL/6Jsuggested: RRID:IMSR_JAX:000664)Software and Algorithms Sentences Resources Statistical analyses were conducted using GraphPad Prism 8.0. 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 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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