Reduced sensitivity of infectious SARS-CoV-2 variant B.1.617.2 to monoclonal antibodies and sera from convalescent and vaccinated individuals
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Abstract
The SARS-CoV-2 B.1.617 lineage emerged in October 2020 in India 1–6 . It has since then become dominant in some indian regions and further spread to many countries. The lineage includes three main subtypes (B1.617.1, B.1617.2 and B.1.617.3), which harbour diverse Spike mutations in the N-terminal domain (NTD) and the receptor binding domain (RBD) which may increase their immune evasion potential. B.1.617.2 is believed to spread faster than the other versions. Here, we isolated infectious B.1.617.2 from a traveller returning from India. We examined its sensitivity to monoclonal antibodies (mAbs) and to antibodies present in sera from COVID-19 convalescent individuals or vaccine recipients, in comparison to other viral lineages. B.1.617.2 was resistant to neutralization by some anti-NTD and anti-RBD mAbs, including Bamlanivimab, which were impaired in binding to the B.1.617.2 Spike. Sera from convalescent patients collected up to 12 months post symptoms and from Pfizer Comirnaty vaccine recipients were 3 to 6 fold less potent against B.1.617.2, relative to B.1.1.7. Sera from individuals having received one dose of AstraZeneca Vaxzevria barely inhibited B.1.617.2. Thus, B.1.617.2 spread is associated with an escape to antibodies targeting non-RBD and RBD Spike epitopes.
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SciScore for 10.1101/2021.05.26.445838: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: This study was approved by the ILE DE FRANCE IV ethical committee.
Consent: At enrolment, written informed consent was collected and participants completed a questionnaire which covered sociodemographic characteristics, virological findings (SARS-CoV-2 RT-PCR results, including date of testing), clinical data (date of symptom onset, type of symptoms, hospitalization), and data related to anti-SARS-CoV-2 vaccination if ever (brand product, date of first and second vaccination).
IRB: This study was approved by Institutional Review Board of Strasbourg University Hospital.Sex as a biological variable not detected. Randomization The experiments were not randomized and the investigators were not … SciScore for 10.1101/2021.05.26.445838: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: This study was approved by the ILE DE FRANCE IV ethical committee.
Consent: At enrolment, written informed consent was collected and participants completed a questionnaire which covered sociodemographic characteristics, virological findings (SARS-CoV-2 RT-PCR results, including date of testing), clinical data (date of symptom onset, type of symptoms, hospitalization), and data related to anti-SARS-CoV-2 vaccination if ever (brand product, date of first and second vaccination).
IRB: This study was approved by Institutional Review Board of Strasbourg University Hospital.Sex as a biological variable not detected. Randomization The experiments were not randomized and the investigators were not blinded to allocation during experiments and outcome assessment. Blinding The experiments were not randomized and the investigators were not blinded to allocation during experiments and outcome assessment. Power Analysis No statistical methods were used to predetermine sample size. Cell Line Authentication Contamination: Cells were tested negative for mycoplasma. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Titration of viral stocks was performed on Vero E6, with a limiting dilution technique allowing a calculation of TCID50, or on S-Fuse cells. Vero E6suggested: NoneSequences were deposited on GISAID immediately after their generation, with the following IDs: D614G: EPI_ISL_414631; B.1.1.7: EPI_ISL_735391; B.1.1.351: EPI_ISL_964916; B.1.617.2: ID: EPI_ISL_2029113. Flow Cytometry: Vero cells with the indicated viral strains at a multiplicity of infection (MOI) of 0.1. Verosuggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)Software and Algorithms Sentences Resources 2 were prepared with The PyMOL Molecular Graphics System, Version 2.1 Schrödinger, LLC. PyMOLsuggested: (PyMOL, RRID:SCR_000305)Statistical analysis: Flow cytometry data were analyzed with FlowJo v10 software (TriStar). FlowJosuggested: (FlowJo, RRID:SCR_008520)Figures were drawn on Prism 9 (GraphPad Software). GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Statistical analysis was conducted using GraphPad Prism 9. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: Thank you for sharing your code.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Potential limitations of our work include a relatively low number of vaccine recipients analyzed and the absence of samples from individuals that received two-doses of AstraZeneca vaccine. We have not analyzed the impact of cellular immunity, which may display higher cross-reactivity than the humoral response. Future work with more individuals and longer survey periods will help characterize the role of humoral responses in vaccine efficacy against the panel of circulating variants. In conclusion, our results demonstrate that the novel emerging B.617.2 variant partially but significantly escapes neutralizing antibodies targeting the NTD and RBD, and polyclonal antibodies elicited by previous SARS-CoV-2 infection or vaccination.
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04750720 Recruiting Study of the Kinetics of COVID-19 Antibodies for 24 Months i… NCT04441684 Recruiting Seroprevalence of SARS-CoV-2 in Strasbourg University Hospit… 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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