Design, immunogenicity, and efficacy of a pan-sarbecovirus dendritic-cell targeting vaccine
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SciScore for 10.1101/2021.12.28.474244: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: All animal procedures (including surgery, anesthesia, and euthanasia, as applicable) used in the current study were submitted to the Institutional Animal Care and Use Committee of the CIPHE approved by the French authorities (CETEA DSV – APAFIS#26484-2020062213431976 v6).
IRB: Ethics approval was given on February 5, 2020, by the French Ethics Committee CPP-Ile-de-France VI (ID RCB: 2020-A00256-33).
Consent: The study was conducted with the understanding and consent of each participant or their surrogate covering the sampling, storage, and use of biological samples.Sex as a biological variable Vaccination and infection of hCD40/K18-hACE2 transgenic mice: Mice of 8 to 12 weeks of age of … SciScore for 10.1101/2021.12.28.474244: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: All animal procedures (including surgery, anesthesia, and euthanasia, as applicable) used in the current study were submitted to the Institutional Animal Care and Use Committee of the CIPHE approved by the French authorities (CETEA DSV – APAFIS#26484-2020062213431976 v6).
IRB: Ethics approval was given on February 5, 2020, by the French Ethics Committee CPP-Ile-de-France VI (ID RCB: 2020-A00256-33).
Consent: The study was conducted with the understanding and consent of each participant or their surrogate covering the sampling, storage, and use of biological samples.Sex as a biological variable Vaccination and infection of hCD40/K18-hACE2 transgenic mice: Mice of 8 to 12 weeks of age of both sexes received two intraperitoneal injections of the CD40.CoV2 vaccine (10 µg) plus polyinosinic-polycytidylic acid (Poly-IC; Oncovir) (50 µg) or poly(IC) alone three weeks apart. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Materials availability: The CD40.CoV2 vaccine generated in this study was deposited in GenBank: anti-human CD40 12E12 antibody IgG4 H chain (GenBank ID: AJD85779.1 residues 20-467) fused to SARS_CoV_2RBD (GenBank ID: UEP92470.1 residues 17-240) followed by EPEA (C-tag) and the anti-human CD40 12E12 antibody kappa L chain (GenBank ID: AJD85780.1 residues 21-236) fused sequentially to a linker (GenBank ID: AJD85777.1 residues 699-725), nucleocapsid phosphoprotein, partial [Severe acute respiratory syndrome coronavirus 2] (GenBank ID: QWE63393.1 residues 95-230), linker residues AR, Chain A, Spike protein S1 [Severe acute respiratory syndrome coronavirus 2] (GenBank ID: 7M8J_A residues 113-237), linker residues TR, and Sequence 12 from patent US 8518410 C-tagsuggested: None[IgG] Kits, MesoScale Discovery, Rockville, MD, USA) were used on all available plasma samples to measure plasma IgG antibodies to SARS-CoV-2, SARS-CoV, MERS-CoV, and HCoVs. plasma IgGsuggested: NoneAntibody concentrations were quantified using a reference standard (ACE2 Calibration Reagent) and are expressed as units/mL (one unit per mL concentration of ACE2 Calibration Reagent corresponds to neutralizing activity of 1 µg/mL monoclonal antibody to SARS-CoV-2 Spike protein). SARS-CoV-2 Spike protein) .suggested: NoneThe flow cytometry panel included a viability marker, CD3, CD4, and CD8 to determine the T-cell lineage, and IFN-γ, TNF, and IL-2 antibodies. CD3suggested: NoneCD4suggested: NoneCD8suggested: NoneTNFsuggested: NoneIL-2 antibodiessuggested: NoneIL-2suggested: NoneExperimental Models: Cell Lines Sentences Resources Infectious stocks were grown by inoculating Vero E6 cells and collecting supernatants upon observation of the cytopathic effect. Vero E6suggested: RRID:CVCL_XD71)Experimental Models: Organisms/Strains Sentences Resources Heterozygous K18-hACE C57BL/6J mice (strain: 2B6.Cg-Tg (K18-ACE2)2Prlmn/J) were obtained from The Jackson Laboratory. C57BL/6Jsuggested: RRID:MGI:3589388)2B6.Cg-Tg ( K18-ACE2)2Prlmn/Jsuggested: NoneFor the AIM assay, PBMCs were stimulated in vitro with various concentrations of the CD40.CoV2 vaccine or an equimolar combination of 15-mer overlapping peptide pools covering the full-length sequence of vaccine antigens (vS1 + vS2 + vRBD + vN2) referred to as vOLPmix. vS1 + vS2 + vRBD + vN2suggested: NoneSoftware and Algorithms Sentences Resources Distributions were plotted using SPICE version 5.22, downloaded from http://exon.niaid.nih.gov/spice (Roederer et al., 2011) SPICEsuggested: (SPICE, RRID:SCR_016603)Statistical analysis: Graphpad Prism software version 8 was used for nonparametric statistics and plots, as described in the figure legends. Graphpad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our study had several limitations. These included the absence of characterization of cross-neutralizing antibodies in vaccinated mice against the B.1.1.529 Omicron variant, which emerged during the writing of this manuscript. However, we could expect that our vaccine would elicit T-cell responses against N epitopes because of the high homology (100%) between vaccine sequences and this VOC. Due to the limited availability of hCD40/K18-hACE2 mice, we did not evaluate various VOC challenges in mice. Finally we favored the analysis of T cell responses using samples from recovered individuals instead of in vivo preclinical models. Although these responses may be dependent on the “clinical history” of patients and their HLA haplotypes, they are less biased than those that would be observed in an animal model. Our results show that the in-vitro vaccine responses are directed against all vaccine proteins, which confirmed the broad HLA coverage of the vaccine sequences. In conclusion, it is becoming urgent to develop a “pan-sarbecovirus vaccine”. The development of a new protein-based vaccine with expected improved tolerability suitable for people with specific vulnerabilities and children would extend the portfolio of current vaccines and be instrumental in controlling the circulation of the virus and the emergence of new variants. By selecting a narrow range of immunodominant epitopes, presented by a wide variety of HLA alleles and less prone to genetic variations across sarbecoviru...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04842682 Recruiting Dose Escalation Trial of CD40.HIVRI.Env Vaccine Combined or … NCT04262921 Recruiting French COVID Cohort 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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