Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice
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Abstract
In the past 20 years, three betacoronaviruses thought to have originated in bats have caused devastating disease in humans. The global pandemic caused by the latest such virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlights the need to protect against other strains that could present a threat to humans. Cohen et al. constructed nanoparticles displaying the protein domain that binds the host cell receptor (receptor-binding domain or RBD), either a homotypic SARS-CoV-2 particle or mosaic particles displaying RBDs from four or eight different betacoronaviruses. In mice, antibodies to the SARS-CoV-2 RBD were elicited just as well by mosaic particles as by homotypic nanoparticles. The mosaic nanoparticles elicited antibodies that, beyond recognizing the strains displayed, also recognized mismatched strains.
Science , this issue p. 735
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SciScore for 10.1101/2020.11.17.387092: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Concentrations of conjugated mi3 particles were determined using a Bio-Rad Protein Assay. Immunizations: Animal procedures and experiments were performed according to protocols approved by the IACUC. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Experiments were done using 4-6 week old female Balb/c mice (Charles River Laboratories), with 5 animals each for cohorts immunized with soluble SARS-CoV-2 S or SpyCatcher003-mi3, and 10 animals each for remaining cohorts (Fig 3A). Table 2: Resources
Antibodies Sentences Resources Half-maximal inhibitory dilutions (ID50 values) were determined using 4-parameter … SciScore for 10.1101/2020.11.17.387092: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Concentrations of conjugated mi3 particles were determined using a Bio-Rad Protein Assay. Immunizations: Animal procedures and experiments were performed according to protocols approved by the IACUC. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Experiments were done using 4-6 week old female Balb/c mice (Charles River Laboratories), with 5 animals each for cohorts immunized with soluble SARS-CoV-2 S or SpyCatcher003-mi3, and 10 animals each for remaining cohorts (Fig 3A). Table 2: Resources
Antibodies Sentences Resources Half-maximal inhibitory dilutions (ID50 values) were determined using 4-parameter nonlinear regression in AntibodyDatabase (57). AntibodyDatabasesuggested: NoneExperimental Models: Organisms/Strains Sentences Resources Experiments were done using 4-6 week old female Balb/c mice (Charles River Laboratories), with 5 animals each for cohorts immunized with soluble SARS-CoV-2 S or SpyCatcher003-mi3, and 10 animals each for remaining cohorts (Fig 3A). Balb/csuggested: NoneSoftware and Algorithms Sentences Resources Phylogenetic tree: A sequence alignment of coronavirus RBD domains was made using Clustal Omega (51). Clustal Omegasuggested: (Clustal Omega, RRID:SCR_001591)A phylogenetic tree was calculated from this amino acid alignment using PhyML 3.0 (52), and a figure of this tree was made using PRESTO (http://www.atgc-montpellier.fr/presto). PhyMLsuggested: (PhyML, RRID:SCR_014629)PRESTOsuggested: (pRESTO, RRID:SCR_001782)Curves were plotted and integrated to obtain the area under the curve (AUC) using Graphpad Prism 8.3 assuming a one-site binding model with a Hill coefficient (Fig. 3; fig. Graphpad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Statistical Analysis: Comparisons between groups for ELISAs and neutralization assays were calculated with one-way analysis of variance (ANOVA) using Tukey’s post hoc test in Prism 9.0 (Graphpad). Prismsuggested: (PRISM, RRID:SCR_005375)For correlation analysis between ELISA and neutralization titers, significance (p), Spearman coefficients (rs), and linear plots were calculated using Prism 9.0 (Graphpad). Graphpadsuggested: (GraphPad, RRID:SCR_000306)Stained cells were analyzed with a SY3200 Cell Sorter (Sony) configured to detect 6 fluorochromes. 2,000,000 events were collected per sample and analyzed via FlowJo software (TreeStar). FlowJosuggested: (FlowJo, RRID:SCR_008520)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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
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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