SARS-CoV-2 variant with higher affinity to ACE2 shows reduced sera neutralization susceptibility
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Abstract
Background
Several new variants of SARS-CoV-2 have emerged since fall 2020 which have multiple mutations in the receptor binding domain (RBD) of the spike protein.
Objective
We aimed to assess how mutations in the SARS-CoV-2 RBD affect receptor affinity to angiotensin-converting enzyme 2 (ACE2) and neutralization by anti-RBD serum antibodies.
Methods
We produced a SARS-CoV-2 RBD mutant (RBDmut) with key mutations (E484K, K417N, N501Y) from the newly emerged Brazilian variant. Using Biolayer Interferometry, we analyzed the binding of this mutant to ACE2, and the susceptibility to neutralization by sera from vaccinated mice and COVID-19 convalescent patients.
Results
Kinetic profiles showed increased RBDmut - ACE2 affinity compared to RBDwt, and binding of vaccine-elicited or convalescent sera was significantly reduced. Likewise, both sera types showed significantly reduced ability to block RBDmut - ACE2 binding indicating that antibodies induced by RBDwt have reduced capability to neutralize mutant virus.
Conclusion
Our physiochemical data show enhanced infectivity and reduced neutralization by polyclonal antibodies of the Brazilian variant of SARS-CoV-2.
Capsule summary
SARS-CoV-2 variant with Brazilian RBD mutations shows increased ACE2 affinity and reduced susceptibility to blockage by vaccine-elicited and convalescent sera.
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SciScore for 10.1101/2021.03.04.433887: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Female mice (8-12 weeks old) were immunized by subcutaneous injection with 40 μg CuMVTT-RBDwt or Tris buffer (20mM Tris + 5mM EDTA, pH 8.0). Table 2: Resources
Antibodies Sentences Resources Bound IgG antibodies were detected with antibody goat anti-mouse IgG-POX antibody (Jackson ImmunoResearch, Cambridgeshire, UK) or goat anti-human IgG-POX antibody (Nordic MUbio, Susteren, The Netherlands). anti-mouse IgG-POXsuggested: Noneanti-human IgG-POXsuggested: NoneExperimental Models: Organisms/Strains Sentences Resources Vaccination of mice: BALB/c mice at the … SciScore for 10.1101/2021.03.04.433887: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Female mice (8-12 weeks old) were immunized by subcutaneous injection with 40 μg CuMVTT-RBDwt or Tris buffer (20mM Tris + 5mM EDTA, pH 8.0). Table 2: Resources
Antibodies Sentences Resources Bound IgG antibodies were detected with antibody goat anti-mouse IgG-POX antibody (Jackson ImmunoResearch, Cambridgeshire, UK) or goat anti-human IgG-POX antibody (Nordic MUbio, Susteren, The Netherlands). anti-mouse IgG-POXsuggested: Noneanti-human IgG-POXsuggested: NoneExperimental Models: Organisms/Strains Sentences Resources Vaccination of mice: BALB/c mice at the age of 7 weeks were purchased from Envigo (NM Horst, The Netherlands) and kept at SPF animal facility of University of Bern. BALB/csuggested: RRID:IMSR_ORNL:BALB/cRl)Software and Algorithms Sentences Resources Unreacted SMPH and RBD proteins were removed using Amicon-Ultra 0.5, 100K (Merck-Millipore, Burlington, Mass). Amicon-Ultrasuggested: NoneData and statistical analysis: All statistical tests were performed using GraphPad PRISM 6.0 (GraphPad Software, Inc.). GraphPad PRISMsuggested: (GraphPad Prism, RRID:SCR_002798)GraphPadsuggested: (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: 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.
- No funding statement was detected.
- No protocol registration statement was detected.
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