One dose of COVID-19 nanoparticle vaccine REVC-128 provides protection against SARS-CoV-2 challenge at two weeks post immunization
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Abstract
A COVID-19 vaccine with capability to induce early protection is needed to efficiently eliminate viral spread. Here, we demonstrate the development of a nanoparticle vaccine candidate, REVC-128, in which multiple trimeric spike ectodomain subunits with glycine (G) at position 614 were multimerized onto a nanoparticle. In-vitro characterization of this vaccine confirms its structural and antigenic integrity. In-vivo immunogenicity evaluation in mice indicates that a single dose of this vaccine induces potent serum neutralizing antibody titer at two weeks post immunization, which is significantly higher than titer induced by trimeric spike protein without nanoparticle presentation. The comparison of serum binding to spike subunits between animals immunized by spike with and without nanoparticle presentation indicates that nanoparticle prefers the display of spike RBD (Receptor-Binding Domain) over S2 subunit, likely resulting in a more neutralizing but less cross-reactive antibody response. Moreover, a Syrian golden hamster in-vivo model for SARS-CoV-2 virus challenge was implemented at two weeks post a single dose of REVC-128 immunization. The results show that vaccination protects hamsters against SARS-CoV-2 virus challenge with evidence of steady body weight, suppressed viral loads and alleviation of tissue damage (lung and nares) for protected animals, compared with ~10% weight loss, higher viral loads and tissue damage in unprotected animals. Furthermore, the data show that vaccine REVC-128 is thermostable at up to 37°C for at least 4 weeks. These findings, along with a long history of safety for protein vaccines, suggest that the REVC-128 is a safe, stable and efficacious single-shot vaccine candidate to induce the earliest protection against SARS-CoV-2 infection.
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SciScore for 10.1101/2021.04.02.438218: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Animal experiments: Animal experiments were carried out in compliance with all pertinent US National Institutes of Health regulations and approval from the Animal Care and Use Committee (ACUC) of Noble Life Sciences and Bioqual. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable For the immunogenicity study, 6-to 8-week-old female C57BL/6 mice (Jackson Laboratory) were inoculated subcutaneously in two sites. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Antibody Fab was captured onto anti-human Fab-CH1 biosensors at concentration of 10 μg/ml as ligand and the tested … SciScore for 10.1101/2021.04.02.438218: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Animal experiments: Animal experiments were carried out in compliance with all pertinent US National Institutes of Health regulations and approval from the Animal Care and Use Committee (ACUC) of Noble Life Sciences and Bioqual. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable For the immunogenicity study, 6-to 8-week-old female C57BL/6 mice (Jackson Laboratory) were inoculated subcutaneously in two sites. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Antibody Fab was captured onto anti-human Fab-CH1 biosensors at concentration of 10 μg/ml as ligand and the tested samples of spike NP or non-NP was diluted in 7 × 2-fold series starting from 250 nM to 3.9 nM in solution, respectively. anti-human Fab-CH1suggested: NoneExperimental Models: Cell Lines Sentences Resources These expression vectors were codon optimized and confirmed by sequencing prior to being transiently transfected into FreeStyle™ 293F cells (Thermo Fisher) 293Fsuggested: RRID:CVCL_D615)VSV-spike pseudovirus production and neutralization assay: To generate SARS-CoV-2 spike VSV pseudovirus, a plasmid encoding SARS-CoV-2 spike harboring a C-terminal 18-residue truncation was transfected into pre-seeded 293T cells. 293Tsuggested: NCBI_Iran Cat# C498, RRID:CVCL_0063)This pseudovirus was first titrated with duplicate on Vero E6 cells cultured in EMEM supplemented with 10% fetal bovine serum and 100 I.U./mL penicillin and 100 μg/mL streptomycin at 37°C. Vero E6suggested: RRID:CVCL_XD71)Experimental Models: Organisms/Strains Sentences Resources For the immunogenicity study, 6-to 8-week-old female C57BL/6 mice (Jackson Laboratory) were inoculated subcutaneously in two sites. C57BL/6suggested: NoneSoftware and Algorithms Sentences Resources Data was fit to a 4PL curve in GraphPad Prism 7. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Single particles were picked with DogPicker and processed in RELION 3.0. RELIONsuggested: (RELION, RRID:SCR_016274)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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