Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies

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Abstract

SARS-CoV-2 B.1.1.7 and B.1.351 variants emerged respectively in United Kingdom and South Africa and spread in many countries. Here, we isolated infectious B.1.1.7 and B.1.351 strains and examined their sensitivity to anti-SARS-CoV-2 antibodies present in sera and nasal swabs, in comparison with a D614G reference virus. We established a novel rapid neutralization assay, based on reporter cells that become GFP+ after overnight infection. B.1.1.7 was neutralized by 79/83 sera from convalescent patients collected up to 9 months post symptoms, almost similar to D614G. There was a mean 6-fold reduction in titers and even loss of activity against B.1.351 in 40% of convalescent sera after 9 months. Early sera from 19 vaccinated individuals were almost as potent against B.1.1.7 but less efficacious against B.1.351, when compared to D614G. Nasal swabs from vaccine recipients were not neutralizing, except in individuals who were diagnosed COVID-19+ before vaccination. Thus, faster-spreading variants acquired a partial resistance to humoral immunity generated by natural infection or vaccination, mostly visible in individuals with low antibody levels.

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  1. SciScore for 10.1101/2021.02.12.430472: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIACUC: 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).
    RandomizationThe experiments were not randomized and the investigators were not blinded to allocation during experiments and outcome assessment Orléans Cohort of convalescent and vaccinated individuals: Orleans’ Cohort of convalescent and/or vaccinated individuals: since April 2020, a prospective, monocentric, longitudinal, cohort clinical study enrolling 170 SARS-CoV-2-infected individuals and 30 non-infected healthy controls is on-going, aiming to describe the persistence of specific and neutralizing antibodies over a 24-months period.
    BlindingThe experiments were not randomized and the investigators were not blinded to allocation during experiments and outcome assessment Orléans Cohort of convalescent and vaccinated individuals: Orleans’ Cohort of convalescent and/or vaccinated individuals: since April 2020, a prospective, monocentric, longitudinal, cohort clinical study enrolling 170 SARS-CoV-2-infected individuals and 30 non-infected healthy controls is on-going, aiming to describe the persistence of specific and neutralizing antibodies over a 24-months period.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line AuthenticationContamination: Cells were tested negative for mycoplasma.

    Table 2: Resources

    Antibodies
    SentencesResources
    The vaccine recipients were tested for anti-S antibodies at Hôpital Européen Georges Pompidou (Paris) with the following assays: Abbott SARS-CoV-2 IgG assays (Des Plaines, IL, USA) targeting SARS-CoV-2 nucleoprotein (N) were performed on Architect™ i2000SR analyzer (Abbott)
    anti-S
    suggested: None
    Antibodies and ACE-2 ectodomain: Human anti-SARS-CoV2 monoclonal antibodies were cloned from S-specific blood memory B cells of Covid19 convalescents (Planchais et al, manuscript in preparation).
    anti-SARS-CoV2
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    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 E6
    suggested: None
    Viruses were sequenced directly on nasal swabs, and after one or two passages on Vero cells.
    Vero
    suggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)
    Briefly, HEK293T (referred as 293T) cells were acquired from ATCC (ATCC® CRL-3216™) and tested negative for mycoplasma.
    HEK293T
    suggested: None
    293T Cells were transfected with the indicated Spike expression plasmids or a control plasmid using Lipofectamine 2000 (Life technologies).
    293T
    suggested: None
    Human anti-S IgG mAbs and His-tagged recombinant ACE2 ectodomain (amino acids 19-615) cloned into pcDNA3.1 vector were produced by transient transfection of Freestyle™ 293-F cells and purified by affinity chromatography as previously described 37
    293-F
    suggested: None
    Software and Algorithms
    SentencesResources
    Commercial serological assays: The serum samples from the Strasbourg cohort were first tested at Hôpital de Strasbourg using two commercial assays: 1) a CE-Marked LFA for detection of IgM and IgG against the SARS-CoV-2 RBD of the S protein developed by Biosynex® (
    Biosynex®
    suggested: None
    The vaccine recipients were tested for anti-S antibodies at Hôpital Européen Georges Pompidou (Paris) with the following assays: Abbott SARS-CoV-2 IgG assays (Des Plaines, IL, USA) targeting SARS-CoV-2 nucleoprotein (N) were performed on Architect™ i2000SR analyzer (Abbott)
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Architect™
    suggested: None
    Results were analysed with FlowJo 10.7.1 (Becton Dickinson).
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Figures were drawn on Prism 9 (GraphPad Software).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Statistical analysis was conducted using GraphPad Prism 9.
    GraphPad Prism
    suggested: (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:
    Potential limitations of our study are the relatively low number of individuals analyzed and the short time frame of analysis after vaccination. Furthermore, we have not investigated the impact of pre-existing cellular immunity, which may be more cross-reactive against variants than the humoral response. Future work with more vaccine recipients that have or haven’t been previously infected, and longer periods of survey, will help characterizing the role of local and systemic humoral responses in vaccine efficacy. In conclusion, our results demonstrate that suboptimal or declining antibody responses are associated with a loss of cross-reactivity against novel emerging viral strains.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04750720RecruitingStudy of the Kinetics of COVID-19 Antibodies for 24 Months i…
    NCT04441684RecruitingSeroprevalence 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.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.