Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine induces equivalent preclinical antibody titers and viral neutralization to recovered COVID-19 patients
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Abstract
The spread of the SARS-CoV-2 into a global pandemic within a few months of onset motivates the development of a rapidly scalable vaccine. Here, we present a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle as a vaccine and demonstrate induction of robust neutralization of a pseudo-virus, proportional to quantity of specific IgG and of higher quantities than recovered COVID-19 patients. These data provide insight into the vaccine design and evaluation of immunogenicity to enable rapid translation to the clinic.
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SciScore for 10.1101/2020.04.22.055608: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: All the procedures and protocols used in this study were approved by an animal ethical committee, the Animal Welfare and Ethical Review Body (AWERB).
Consent: Recovered COVID-19 patient samples: Serum samples were donated to the Communicable Diseases Research Tissue Bank, Section of Virology, Imperial College London, following written informed consent, by patients who had been infected with SARS-CoV-2.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Plates were incubated for 1 h at 37ºC, then washed and … SciScore for 10.1101/2020.04.22.055608: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: All the procedures and protocols used in this study were approved by an animal ethical committee, the Animal Welfare and Ethical Review Body (AWERB).
Consent: Recovered COVID-19 patient samples: Serum samples were donated to the Communicable Diseases Research Tissue Bank, Section of Virology, Imperial College London, following written informed consent, by patients who had been infected with SARS-CoV-2.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Plates were incubated for 1 h at 37ºC, then washed and secondary antibody added at 1:2000 dilution in blocking buffer (100 μL/well) using either anti-mouse IgG-HRP, anti-mouse IgG1-HRP or anti-mouse IgG2a-HRP (Southern Biotech). anti-mouse IgG-HRPsuggested: Noneanti-mouse IgG1-HRPsuggested: Noneanti-mouse IgG2a-HRPsuggested: NoneExperimental Models: Cell Lines Sentences Resources Cell Culture & saRNA Transfection: HEK293T/17 cells (ATCC) were cultured in complete Dulbecco’s Modified Eagle’s Medium (DMEM) (Gibco, Thermo Fisher Scientific) containing 10 % fetal bovine serum (FBS, Gibco, Thermo Fisher Scientific), 1 % L-glutamine and 1 % penicillin-streptomycin (Thermo Fisher Scientific) at 37°C, 5% CO₂. HEK293T/17suggested: NoneFor the neutralization assay, heat-inactivated sera were first serially diluted and incubated with virus for 1 h, and then the serum-virus mixture was transferred into wells pre-seeded Caco2 cells. Caco2suggested: CLS Cat# 300137/p1665_CaCo-2, RRID:CVCL_0025)Experimental Models: Organisms/Strains Sentences Resources 7 Animals and immunizations: BALB/c mice aged 6-8 weeks old were placed into groups of n = 7 or 8. BALB/csuggested: NoneSoftware and Algorithms Sentences Resources Samples were analyzed on a LSRForterssa (BD Biosciences) with FACSDiva software (BD Biosciences). FACSDivasuggested: (BD FACSDiva Software, RRID:SCR_001456)FlowJo LLC). FlowJosuggested: (FlowJo, RRID:SCR_008520)The IC50 neutralization was then calculated using GraphPad Prism (version 8.4). 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.
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SciScore for 10.1101/2020.04.22.055608: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources We observed that two saRNA LNP immunizations induced remarkably high SARS-CoV-2 specific IgG antibodies in mice, with quantities that were superior to both EP pDNA and natural infection in humans, that were able to efficiently neutralize a pseudotyped virus. specific IgGsuggested: NoneResults from OddPub: We did not find a statement about open data. We also did not find a statement about open code. Researchers are …
SciScore for 10.1101/2020.04.22.055608: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources We observed that two saRNA LNP immunizations induced remarkably high SARS-CoV-2 specific IgG antibodies in mice, with quantities that were superior to both EP pDNA and natural infection in humans, that were able to efficiently neutralize a pseudotyped virus. specific IgGsuggested: NoneResults from OddPub: We did not find a statement about open data. We also did not find a statement about open code. Researchers are encouraged to share open data when possible (see Nature blog).
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