SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral Spike vaccines
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Abstract
The SARS-CoV-2 Spike glycoprotein mediates virus entry and is a major target for neutralizing antibodies. All current vaccines are based on the ancestral Spike with the goal of generating a protective neutralizing antibody response. Several novel SARS-CoV-2 variants with multiple Spike mutations have emerged, and their rapid spread and potential for immune escape have raised concerns. One of these variants, first identified in the United Kingdom, B.1.1.7 (also called VUI202012/01), contains eight Spike mutations with potential to impact antibody therapy, vaccine efficacy and risk of reinfection. Here we employed a lentivirus-based pseudovirus assay to show that variant B.1.1.7 remains sensitive to neutralization, albeit at moderately reduced levels (~2-fold), by serum samples from convalescent individuals and recipients of two different vaccines based on ancestral Spike: mRNA-1273 (Moderna), and protein nanoparticle NVX-CoV2373 (Novavax). Some monoclonal antibodies to the receptor binding domain (RBD) of Spike were less effective against the variant while others were largely unaffected. These findings indicate that B.1.1.7 is not a neutralization escape variant that would be a major concern for current vaccines, or for an increased risk of reinfection.
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SciScore for 10.1101/2021.01.27.428516: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethics Statement: Clinical trials described in this manuscript were approved by the appropriate Institutional Review Boards ( Randomization Samples tested were randomly collected and not pre-selected for higher titer respones at 2 weeks post 2nd inoculation (day 35). 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 Antibodies B38, H4, P2B-2F6, and S309 (42–44), were provided by Dr. Peter Kwong. H4suggested: NoneS309suggested: NoneAntibodies DH1041, DH1042, DH1043, and DH1047 were provided by Drs. DH1042suggested: NoneDH1043suggested: NoneStru… SciScore for 10.1101/2021.01.27.428516: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethics Statement: Clinical trials described in this manuscript were approved by the appropriate Institutional Review Boards ( Randomization Samples tested were randomly collected and not pre-selected for higher titer respones at 2 weeks post 2nd inoculation (day 35). 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 Antibodies B38, H4, P2B-2F6, and S309 (42–44), were provided by Dr. Peter Kwong. H4suggested: NoneS309suggested: NoneAntibodies DH1041, DH1042, DH1043, and DH1047 were provided by Drs. DH1042suggested: NoneDH1043suggested: NoneStructural analyses: We used PDB: 7C2L (50) for the full trimeric spike structure, and antibody spike complex structures from Li et al. (45) for DH1041-DH1047 antibodies, PDB: 6WPS (44) for S309, PDB: 7BWJ (43) for P2B-2F6, and PDB: 6XDG for REGN antibodies (51). DH1041-DH1047suggested: NoneP2B-2F6suggested: NoneFor B38, to identify the most amenable Y-501 rotamers, the N501Y mutation was modeled with the antibody-RBD complex; however, all identified rotamers induced substantial clashes and the rotamer with the least clash was retained. antibody-RBDsuggested: NoneExperimental Models: Cell Lines Sentences Resources Transfection mixtures were added to pre-seeded HEK 293T/17 cells in T-75 flasks containing 12 ml of growth medium and incubated for 16-20 hours at 37°C. HEK 293T/17suggested: ATCC Cat# CRL-11268, RRID:CVCL_1926)Software and Algorithms Sentences Resources Antibody epitope, electrostatics and polar bonds calculations as well as mutation modeling were performed in PyMOL (The PyMOL Molecular Graphics System, Version 2.0 Schrödinger, LLC.). PyMOLsuggested: (PyMOL, RRID:SCR_000305)To correct for multiple test corrections, false discovery rates (FDR or q values) were calculated as in (52) implemented in a Python package (https://github.com/nfusi/qvalue) for Python version 3.4.2. Pythonsuggested: (IPython, RRID:SCR_001658)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 NCT04283461 Active, not recruiting Safety and Immunogenicity Study of 2019-nCoV Vaccine (mRNA-1… NCT04470427 Active, not recruiting A Study to Evaluate Efficacy, Safety, and Immunogenicity of … NCT04368988 Active, not recruiting Evaluation of the Safety and Immunogenicity of a SARS-CoV-2 … NCT04403880 Recruiting Characterizing SARS-CoV-2-specific Immunity in Individuals W… 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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