Immune escape of SARS-CoV-2 Omicron variant from mRNA vaccination-elicited RBD-specific memory B cells
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Abstract
Memory B cells (MBCs) represent a second layer of immune protection against SARS-CoV-2. Whether MBCs elicited by mRNA vaccines can recognize the Omicron variant is of major concern. We used bio-layer interferometry to assess the affinity against the receptor-binding-domain (RBD) of Omicron spike of 313 naturally expressed monoclonal IgG that were previously tested for affinity and neutralization against VOC prior to Omicron. We report here that Omicron evades recognition from a larger fraction of these antibodies than any of the previous VOCs. Additionally, whereas 30% of these antibodies retained high affinity against Omicron-RBD, our analysis suggest that Omicron specifically evades antibodies displaying potent neutralizing activity against the D614G and Beta variant viruses. Further studies are warranted to understand the consequences of a lower memory B cell potency on the overall protection associated with current vaccines.
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SciScore for 10.1101/2021.12.21.473528: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources anti-Human Fc Capture (AHC) biosensors (18-5060) were immersed in supernatants from single-cell memory B cell culture (or control monoclonal antibody) at 25°C for 1800 seconds. anti-Human Fc Capture ( AHCsuggested: NoneAll mAbs with ratio superior to two for these two combinations were labeled as binding both the N501 and K417 residues, as previously described for RBS-A type of anti-RBD mAbs (Yuan et al., 2021); 2/ mAbs affected by the B.1.351, P.1, B.1.617.1 and B.1.617.2 variants, … SciScore for 10.1101/2021.12.21.473528: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources anti-Human Fc Capture (AHC) biosensors (18-5060) were immersed in supernatants from single-cell memory B cell culture (or control monoclonal antibody) at 25°C for 1800 seconds. anti-Human Fc Capture ( AHCsuggested: NoneAll mAbs with ratio superior to two for these two combinations were labeled as binding both the N501 and K417 residues, as previously described for RBS-A type of anti-RBD mAbs (Yuan et al., 2021); 2/ mAbs affected by the B.1.351, P.1, B.1.617.1 and B.1.617.2 variants, but not the B.1.1.7 variant, were labeled as binding both the E484 and L452 residues based on reported data in the literature for RBS-B/C antibodies (Yuan et al., 2021; Starr et al., 2021). anti-RBDsuggested: NoneRBS-B/Csuggested: NoneCells were fixed with 4% formaldehyde and foci were revealed using a rabbit anti-SARS-CoV-2 N antibody (gift of Nicolas Escriou) and anti-rabbit secondary HRP-conjugated secondary antibody. anti-SARS-CoV-2 Nsuggested: Noneanti-rabbitsuggested: NoneExperimental Models: Cell Lines Sentences Resources Vero E6 cells were seeded at 2×104 cells/well in a 96-well plate 24h before the assay. Vero E6suggested: NoneRecombinant DNA Sentences Resources Recombinant protein purification: Construct design: The SARS-CoV-2 Receptor Binding Domain (RBD) was cloned in pcDNA3.1(+) encompassing the Spike (S) residues 331-528, and it was flanked by an N-terminal IgK signal peptide and a C-terminal Thrombin cleavage site followed by Hisx8, Strep and Avi tags. pcDNA3.1suggested: RRID:Addgene_79663)Software and Algorithms Sentences Resources Sequence quality was verified with the CodonCode Aligner software (CodonCode Corporation) CodonCode Alignersuggested: NoneComputational analyses of VDJ sequences: Processed FASTA sequences from cultured single-cell VH sequencing were annotated using Igblast v1.16.0 against the human IMGT reference database. Igblastsuggested: (IgBLAST, RRID:SCR_002873)VH repartition was calculated using the countGenes() function from the Immcantation/alakazam v1.1.0 R package. Immcantation/alakazamsuggested: None3D representation of known mutations to the RBD surface: Panel D in Figure 5 was prepared with The PyMOL Molecular Graphics System, Version 2.1 Schrödinger, LLC. PyMOLsuggested: (PyMOL, RRID:SCR_000305)Quantification and Statistical Analysis: Statistical analyses were all performed using GraphPad Prism 9.0 (La Jolla, CA, USA). 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: We detected the following sentences addressing limitations in the study:A limitation to our conclusions relies in the fact that samples analyzed were collected early after the first vaccine boost in all individuals. The repertoire of COVID-19-naive vaccinated individuals has been shown to evolve up to 5 months after the boost (Cho et al., 2021; Goel et al., 2021a) and it remains to be assessed how this MBC repertoire will further evolve after an additional vaccine boost, with a third dose of the Wuhan (WT) spike mRNA vaccine currently being implemented in numerous countries. Additionally, our study was focused on the RBD domain of the SARS-CoV-2 spike protein, which represents the major target of neutralizing antibodies. However, neutralizing antibodies against other domains of the trimeric spike have been described, notably against the N-terminal domain (NTD) and these might be affected in a different way (Tong et al., 2021). A similar point could be made for memory T cell responses, which appear so far to be less affected by mutations selected by SARS-CoV-2 variants (Goel et al., 2021b). Answering these questions will provide us with crucial information regarding the available immune protection against Omicron or subsequent variants, and allow an informed decision as to whether vaccine specifically targeted against VOCs will need to be implemented in the near future.
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04402892 Not yet recruiting COVID-19: SARS-CoV-2 Specific Memory B and T-CD4+ Cells 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.
Results from scite Reference Check: We found no unreliable references.
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