Soluble Spike DNA Vaccine Provides Long-Term Protective Immunity against SARS-CoV-2 in Mice and Nonhuman Primates
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Abstract
The unprecedented and rapid spread of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) has motivated the need for a rapidly producible and scalable vaccine. Here, we developed a synthetic soluble SARS-CoV-2 spike (S) DNA-based vaccine candidate, GX-19. In mice, immunization with GX-19 elicited not only S-specific systemic and pulmonary antibody responses but also Th1-biased T cell responses in a dose-dependent manner. GX-19-vaccinated nonhuman primates seroconverted rapidly and exhibited a detectable neutralizing antibody response as well as multifunctional CD4+ and CD8+ T cell responses. Notably, when the immunized nonhuman primates were challenged at 10 weeks after the last vaccination with GX-19, they had reduced viral loads in contrast to non-vaccinated primates as a control. These findings indicate that GX-19 vaccination provides a durable protective immune response and also support further development of GX-19 as a vaccine candidate for SARS-CoV-2.
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SciScore for 10.1101/2020.10.09.334136: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Immunization procedures were approved by the Institutional Animal Care and Use Committee (IACUC permit number ORIENT-IACUC-20044), and challenging procedures were approved by KRIBB IACUC (permit number KRIBB-AEC-20178). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Mouse immunizations: Female BALB/c mice aged 6-8 weeks (Koatech) were immunized with GX-19 vaccine or pGX27 in a total volume of 50 μl of PBS into the tibialis anterior muscle with in vivo electroporation with OrbiJector® (SL VAXiGEN Inc.) at weeks 0, 2. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources ELISPO… SciScore for 10.1101/2020.10.09.334136: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Immunization procedures were approved by the Institutional Animal Care and Use Committee (IACUC permit number ORIENT-IACUC-20044), and challenging procedures were approved by KRIBB IACUC (permit number KRIBB-AEC-20178). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Mouse immunizations: Female BALB/c mice aged 6-8 weeks (Koatech) were immunized with GX-19 vaccine or pGX27 in a total volume of 50 μl of PBS into the tibialis anterior muscle with in vivo electroporation with OrbiJector® (SL VAXiGEN Inc.) at weeks 0, 2. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources ELISPOT plates were coated with purified anti-mouse IFN-γ capture antibody and incubated overnight at 4°C. anti-mouse IFN-γsuggested: NoneAntibodies for staining cells were CD8 FITC (Biolegend 100706), IL-2 PE (Biolegend 503808) IL-2 PEsuggested: (BioLegend Cat# 503808, RRID:AB_315302)Antibodies for staining cells were CD3 PE (BD bioscience 552127), CD4 PerCP-Cy5.5 (Biolegend 317428) CD4suggested: (BioLegend Cat# 317428, RRID:AB_1186122)Experimental Models: Cell Lines Sentences Resources 30 μl of TrueBlue solution was added on the Vero cells and incubate at room temperature for 30 minutes. Verosuggested: NoneExperimental Models: Organisms/Strains Sentences Resources Mouse immunizations: Female BALB/c mice aged 6-8 weeks (Koatech) were immunized with GX-19 vaccine or pGX27 in a total volume of 50 μl of PBS into the tibialis anterior muscle with in vivo electroporation with OrbiJector® (SL VAXiGEN Inc.) at weeks 0, 2. BALB/csuggested: NoneSoftware and Algorithms Sentences Resources , IgG1 (Jackson ImmunoResearch Laboratories 115-035-205), or IgG2a (Jackson ImmunoResearch Laboratories 115-035-206) or IgG2b (Jackson ImmunoResearch Laboratories 115-035-207) for the mouse sera/BAL or anti-monkey IgG (Bethyl Laborabories A140-102P) for the NHP sera for 1 hour at 37°C. Bethyl Laboraboriessuggested: NoneThe numbers of focus of each well were read using CTL reader (Cellular Technology Ltd.) and the neutralizing Ab titers were calculated using Microsoft Excel and SoftMax (Version 5.4.1.) Microsoft Excelsuggested: (Microsoft Excel, RRID:SCR_016137)Fluorescence-activated cell sorting analysis was accomplished by Fortessa flow cytometer (BD bioscience), and the data were analyzed using FlowJo software. FlowJosuggested: (FlowJo, RRID:SCR_008520)Statistical analysis: Analysis of virologic and immunologic data was performed using GraphPad Prism 5 (GraphPad Software). GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)GraphPadsuggested: (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.
- No funding statement was detected.
- No protocol registration statement was detected.
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