A broadly neutralizing antibody protects against SARS-CoV, pre-emergent bat CoVs, and SARS-CoV-2 variants in mice
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
SARS-CoV in 2003, SARS-CoV-2 in 2019, and SARS-CoV-2 variants of concern (VOC) can cause deadly infections, underlining the importance of developing broadly effective countermeasures against Group 2B Sarbecoviruses, which could be key in the rapid prevention and mitigation of future zoonotic events. Here, we demonstrate the neutralization of SARS-CoV, bat CoVs WIV-1 and RsSHC014, and SARS-CoV-2 variants D614G, B.1.1.7, B.1.429, B1.351 by a receptor-binding domain (RBD)-specific antibody DH1047. Prophylactic and therapeutic treatment with DH1047 demonstrated protection against SARS-CoV, WIV-1, RsSHC014, and SARS-CoV-2 B1.351infection in mice. Binding and structural analysis showed high affinity binding of DH1047 to an epitope that is highly conserved among Sarbecoviruses. We conclude that DH1047 is a broadly neutralizing and protective antibody that can prevent infection and mitigate outbreaks caused by SARS-like strains and SARS-CoV-2 variants. Our results argue that the RBD conserved epitope bound by DH1047 is a rational target for pan Group 2B coronavirus vaccines.
Article activity feed
-
SciScore for 10.1101/2021.04.27.441655: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: The study was carried out in accordance with the recommendations for care and use of animals by the Office of Laboratory Animal Welfare (OLAW), National Institutes of Health and the Institutional Animal Care and Use Committee (IACUC) of University of North Carolina (UNC permit no. A-3410-01). Sex as a biological variable Animals and challenge viruses: Eleven-month-old female BALB/c mice were purchased from Envigo (#047) and were used for the SARS-CoV, SARS-CoV-2 B1.351, and RsSHC014-CoV protection experiments. 8-10-week-old hACE2-transgenic mice were bred at UNC Chapel Hill and were used for WIV-1-CoV protection experiments. Randomization In a blinded manner, three random fields of lung … SciScore for 10.1101/2021.04.27.441655: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: The study was carried out in accordance with the recommendations for care and use of animals by the Office of Laboratory Animal Welfare (OLAW), National Institutes of Health and the Institutional Animal Care and Use Committee (IACUC) of University of North Carolina (UNC permit no. A-3410-01). Sex as a biological variable Animals and challenge viruses: Eleven-month-old female BALB/c mice were purchased from Envigo (#047) and were used for the SARS-CoV, SARS-CoV-2 B1.351, and RsSHC014-CoV protection experiments. 8-10-week-old hACE2-transgenic mice were bred at UNC Chapel Hill and were used for WIV-1-CoV protection experiments. Randomization In a blinded manner, three random fields of lung tissue were chosen and scored for the following: (A) neutrophils in the alveolar space (none = 0, 1–5 cells = 1, > 5 cells = 2), (B) neutrophils in the interstitial septa (none = 0, 1–5 cells = 1, > 5 cells = 2), (C) hyaline membranes (none = 0, one membrane = 1, > 1 membrane = 2), (D) Proteinaceous debris in air spaces (none = 0, one instance = 1, > 1 instance = 2), (E) alveolar septal thickening (< 2x mock thickness = 0, 2–4x mock thickness = 1, > 4x mock thickness = 2). Blinding Analyses and scoring were performed by a board vertified veterinary pathologist who was blinded to the treatment groups as described previously 48. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources HRP conjugated goat anti-mouse IgG secondary antibody (SouthernBiotech 1030-05) was diluted to 1:10,000 in assay diluent without azide, incubated at for 1 hour at room temperature, washed and detected with 20μl SureBlue Reserve (KPL 53-00-03) for 15 minutes. anti-mouse IgGsuggested: (SouthernBiotech Cat# 1030-05, RRID:AB_2619742)Antibody-virus and virus only mixtures were then incubated at 37°C with 5% CO2 for one hour. Antibody-virussuggested: NoneExperimental Models: Cell Lines Sentences Resources For the 96-well neutralization assay, Vero E6 USAMRID cells were plated at 20,000 cells per well the day prior in clear bottom black walled plates. Vero E6suggested: NoneExperimental Models: Organisms/Strains Sentences Resources Animals and challenge viruses: Eleven-month-old female BALB/c mice were purchased from Envigo (#047) and were used for the SARS-CoV, SARS-CoV-2 B1.351, and RsSHC014-CoV protection experiments. 8-10-week-old hACE2-transgenic mice were bred at UNC Chapel Hill and were used for WIV-1-CoV protection experiments. BALB/csuggested: NonehACE2-transgenicsuggested: NoneSoftware and Algorithms Sentences Resources The RELION 3.0 program was used for all negative stain image processing. RELIONsuggested: (RELION, RRID:SCR_016274)Data processing was performed using cryoSPARC 39. cryoSPARCsuggested: (cryoSPARC, RRID:SCR_016501)Model building and refinement was done using Phenix 40,41 Phenixsuggested: (Phenix, RRID:SCR_014224), Coot 42 Cootsuggested: (Coot, RRID:SCR_014222), Pymol 43, Chimera 44, ChimeraX 45 and Isolde 46. Pymolsuggested: (PyMOL, RRID:SCR_000305)Statistics: All statistical analyses were performed using GraphPad Prism 9. 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: Please consider improving the rainbow (“jet”) colormap(s) used on page 46. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
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.
-