SARS-CoV-2 vaccination induces neutralizing antibodies against pandemic and pre-emergent SARS-related coronaviruses in monkeys
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
Betacoronaviruses (betaCoVs) caused the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, and now the SARS-CoV-2 pandemic. Vaccines that elicit protective immune responses against SARS-CoV-2 and betaCoVs circulating in animals have the potential to prevent future betaCoV pandemics. Here, we show that immunization of macaques with a multimeric SARS-CoV-2 receptor binding domain (RBD) nanoparticle adjuvanted with 3M-052-Alum elicited cross-neutralizing antibody responses against SARS-CoV-1, SARS-CoV-2, batCoVs and the UK B.1.1.7 SARS-CoV-2 mutant virus. Nanoparticle vaccination resulted in a SARS-CoV-2 reciprocal geometric mean neutralization titer of 47,216, and robust protection against SARS-CoV-2 in macaque upper and lower respiratory tracts. Importantly, nucleoside-modified mRNA encoding a stabilized transmembrane spike or monomeric RBD protein also induced SARS-CoV-1 and batCoV cross-neutralizing antibodies, albeit at lower titers. These results demonstrate current mRNA vaccines may provide some protection from future zoonotic betaCoV outbreaks, and provide a platform for further development of pan-betaCoV nanoparticle vaccines.
Article activity feed
-
SciScore for 10.1101/2021.02.17.431492: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: The study protocol and all veterinarian procedures were approved by the Bioqual IACUC per a memorandum of understanding with the Duke IACUC, and were performed based on standard operating procedures. Randomization For clusters of size >5, 5 spike sequences were randomly downsampled from each cluster. 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 To measure dissociation of the antibody-RBD-scNP complex, the tip was incubated in PBS for 600 s. antibody-RBD-scNPsuggested: NonePlasma IgG blocking of RBD monoclonal antibody binding: … SciScore for 10.1101/2021.02.17.431492: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: The study protocol and all veterinarian procedures were approved by the Bioqual IACUC per a memorandum of understanding with the Duke IACUC, and were performed based on standard operating procedures. Randomization For clusters of size >5, 5 spike sequences were randomly downsampled from each cluster. 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 To measure dissociation of the antibody-RBD-scNP complex, the tip was incubated in PBS for 600 s. antibody-RBD-scNPsuggested: NonePlasma IgG blocking of RBD monoclonal antibody binding: Blocking assays for DH1041 and DH1047 were performed as stated above for ACE2, except plates were coated with either DH1041 or DH1047 instead of ACE2. ACE2suggested: NoneAntibody-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 The SARS-CoV-2 RBD was expressed in Freestyle293 cells and purified by StrepTactin affinity chromatography (IBA) and superdex200 size exclusion chromatography as stated above. Freestyle293suggested: ATCC Cat# PTA-5080, RRID:CVCL_D603)Pseudovirions were produced in HEK 293T/17 cells (ATCC cat. no. CRL-11268) by transfection using Fugene 6 (Promega, Catalog #E2692). HEK 293T/17suggested: ATCC Cat# CRL-11268, RRID:CVCL_1926)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: NoneSoftware and Algorithms Sentences Resources The binding response at the end of the 400 s association phase was plotted in GraphPad Prism v9.0. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Processing of negative stain images: The RELION 3.0 program was used for all negative stain image processing. RELIONsuggested: (RELION, RRID:SCR_016274)Betacoronavirus sequence analysis: Heatmaps of amino acid sequence similarity were computed for a representative set of betacoronaviruses using the ComplexHeatmap package in R. ComplexHeatmapsuggested: (ComplexHeatmap, RRID:SCR_017270)To map group 2b betaCoV sequence conservation onto the RBD structure, group 2b spike sequences were retrieved from Genbank and clustered using USEARCH 67 with a sequence identity threshold of 0.99 resulting in 39 clusters. USEARCHsuggested: (mubiomics, RRID:SCR_006785)The resulting set of 73 sequences was aligned using MAFFT 68. MAFFTsuggested: (MAFFT, RRID:SCR_011811)The conservation scores were then mapped to the RBD domain coordinates (PDB: 7LD1) and images rendered with PyMol version 2.3.5. PyMolsuggested: (PyMOL, RRID:SCR_000305)Statistics Analysis: Data were plotted using Prism GraphPad 8.0. GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Wilcoxon rank sum exact test was performed to compare differences between groups with p-value < 0.05 considered significant using SAS 9.4 (SAS Institute, Cary, NC). SAS Institutesuggested: (Statistical Analysis System, RRID:SCR_008567)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: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04177355 Recruiting Evaluating the Safety and Immunogenicity of HIV-1 BG505 SOSI… 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 34. 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.
-