SARS-CoV-2 evolution and patient immunological history shape the breadth and potency of antibody-mediated immunity

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Since the emergence of SARS-CoV-2, humans have been exposed to distinct SARS-CoV-2 antigens, either by infection with different variants, and/or vaccination. Population immunity is thus highly heterogeneous, but the impact of such heterogeneity on the effectiveness and breadth of the antibody-mediated response is unclear. We measured antibody-mediated neutralisation responses against SARS-CoV-2 Wuhan , SARS-CoV-2α, SARS-CoV-2δ and SARS-CoV-2ο pseudoviruses using sera from patients with distinct immunological histories, including naive, vaccinated, infected with SARS-CoV-2 Wuhan , SARS-CoV-2α or SARS-CoV-2δ, and vaccinated/infected individuals. We show that the breadth and potency of the antibody-mediated response is influenced by the number, the variant, and the nature (infection or vaccination) of exposures, and that individuals with mixed immunity acquired by vaccination and natural exposure exhibit the broadest and most potent responses. Our results suggest that the interplay between host immunity and SARS-CoV-2 evolution will shape the antigenicity and subsequent transmission dynamics of SARS-CoV-2, with important implications for future vaccine design.

Author Summary

Neutralising antibodies provide protection against viruses and are generated because of vaccination or prior infections. The main target of anti-SARS-CoV-2 neutralising antibodies is a protein called Spike, which decorates the viral particle and mediates viral entry into cells. As SARS-CoV-2 evolves, mutations accumulate in the spike protein, allowing the virus to escape antibody-mediated immunity and decreasing vaccine effectiveness. Multiple SARS-CoV-2 variants have appeared since the start of the COVID-19 pandemic, causing various waves of infection through the population and infecting-in some cases-people that had been previously infected or vaccinated. Since the antibody response is highly specific, individuals infected with different variants are likely to have different repertoires of neutralising antibodies. We studied the breadth and potency of the antibody-mediated response against different SARS-CoV-2 variants using sera from vaccinated people as well as from people infected with different variants. We show that potency of the antibody response against different SARS-CoV-2 variants depends on the particular variant that infected each person, the exposure type (infection or vaccination) and the number and order of exposures. Our study provides insight into the interplay between virus evolution and immunity, as well as important information for the development of better vaccination strategies.

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  1. SciScore for 10.1101/2022.05.06.490867: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethics statement: Ethical approval was provided by NHSGGC Biorepository (application 550).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    Cells: HEK293T and 293-ACE2 cells were maintained at 37°C, 5% CO2, in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% foetal bovine serum, 2mM L-glutamine, 100μg/ml streptomycin and 100 IU/ml penicillin.
    suggested: None
    suggested: RRID:CVCL_DR94)
    HEK293 cells were used to produce HEK293-ACE2 target cells by stable transduction with pSCRPSY-hACE2 and were maintained in complete DMEM supplemented with 2μg/ml puromycin.
    suggested: None
    Recombinant DNA
    HEK293 cells were used to produce HEK293-ACE2 target cells by stable transduction with pSCRPSY-hACE2 and were maintained in complete DMEM supplemented with 2μg/ml puromycin.
    suggested: None
    HEK293T cells were transfected with the appropriate SARS-CoV-2 Spike gene expression vector (Wuhan, Alpha, Delta, or Omicron) together with p8.9171 and pCSFLW72 using polyethylenimine (PEI, Polysciences, Warrington, USA).
    suggested: None
    Software and Algorithms
    All analyses and data visualisations were executed using the stats[25] and ggplot2[26] packages respectively, from R version 4.0.5.
    suggested: (ggplot2, RRID:SCR_014601)

    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.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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