Neutralization capacity of antibodies elicited through homologous or heterologous infection or vaccination against SARS-CoV-2 VOCs

  1. Meriem Bekliz
  2. Kenneth Adea
  3. Pauline Vetter
  4. Christiane S. Eberhardt
  5. Krisztina Hosszu-Fellous
  6. Diem-Lan Vu
  7. Olha Puhach
  8. Manel Essaidi-Laziosi
  9. Sophie Waldvogel-Abramowski
  10. Caroline Stephan
  11. Arnaud G. L’Huillier
  12. Claire-Anne Siegrist
  13. Arnaud M. Didierlaurent
  14. Laurent Kaiser
  15. Benjamin Meyer
  16. Isabella Eckerle

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Abstract

Emerging SARS-CoV-2 variants raise questions about escape from previous immunity. As the population immunity to SARS-CoV-2 has become more complex due to prior infections with different variants, vaccinations or the combination of both, understanding the antigenic relationship between variants is needed. Here, we have assessed neutralizing capacity of 120 blood specimens from convalescent individuals infected with ancestral SARS-CoV-2, Alpha, Beta, Gamma or Delta, double vaccinated individuals and patients after breakthrough infections with Delta or Omicron-BA.1. Neutralization against seven authentic SARS-CoV-2 isolates (B.1, Alpha, Beta, Gamma, Delta, Zeta and Omicron-BA.1) determined by plaque-reduction neutralization assay allowed us to map the antigenic relationship of SARS-CoV-2 variants. Highest neutralization titers were observed against the homologous variant. Antigenic cartography identified Zeta and Omicron-BA.1 as separate antigenic clusters. Substantial immune escape in vaccinated individuals was detected for Omicron-BA.1 but not Zeta. Combined infection/vaccination derived immunity results in less Omicron-BA.1 immune escape. Last, breakthrough infections with Omicron-BA.1 lead to broadly neutralizing sera.

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  1. Version published to 10.1038/s41467-022-31556-1
  2. Version published to 10.1101/2021.12.28.21268491v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.12.28.21268491: (What is this?)

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

    Table 1: Rigor

    EthicsField Sample Permit: In addition, anonymized left-over samples from apheresis collection of plasma (all collected in 2020) were available under the general informed consent of the University Hospitals of Geneva.
    Consent: In addition, anonymized left-over samples from apheresis collection of plasma (all collected in 2020) were available under the general informed consent of the University Hospitals of Geneva.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    All vaccinated individuals were in addition tested for the presence of nucleocapsid antibodies (Elecsys® Anti-SARS-CoV-2 anti-N) to screen for unrecognized infection prior to vaccination.
    anti-N
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Viruses and cells: Vero-E6 and Vero E6-TMPRSS cells were cultured in complete DMEM GlutaMax I medium supplemented with 10% fetal bovine serum, 1x Non-essential Amino Acids, and 1% antibiotics (Penicillin/Streptomycin) (all reagents from Gibco, USA).
    Vero E6-TMPRSS
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    Briefly, no primary Beta isolate could be obtained on VeroE6 but only on A549 cells overexpressing human ACE2 [23].
    A549
    suggested: NCI-DTP Cat# A549, RRID:CVCL_0023)
    Therefore, after primary isolation, A549-hACE2 cells were mixed with VeroE6 in a 1:1 ratio and inoculated with the passage 1 isolate.
    A549-hACE2
    suggested: RRID:CVCL_A5KB)
    The Omicron variant was primarily isolated on Vero-TMPRSS cells, then transferred to Vero E6 for generation of a virus stock.
    Vero E6
    suggested: RRID:CVCL_XD71)
    All virus stocks were titrated on Vero-E6 cells and full genome sequenced.
    Vero-E6
    suggested: None
    Software and Algorithms
    SentencesResources
    The 90% reduction endpoint titers (PRNT90) were calculated by fitting a 4-parameter logistics curve with variable slope to the plaque counts of each serum/plasma using GraphPad Prism version 9.2.0.
    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:
    Limitations of our study are the relatively low number of specimens that were available for convalescent specimens of patients previously infected with variants. Furthermore, we cannot exclude that individuals infected with a VOC have not already been infected in 2020 with a first-wave virus and thus antibodies are derived from multiple infections with more than one variant. In addition, the Beta variant, which could not be readily isolated on VeroE6 cell lines had to be adapted to VeroE6 in order to be usable for our PRNT, thus the isolate accumulated mutations, which could affect the neutralization results. No convalescent samples were available from individuals infected with Zeta, and no convalescent samples were yet available from individuals infected with Omicron without prior vaccination. Furthermore, testing of single time points after infection/vaccination can only provide a snapshot and not inform on the duration of antibody responses over time. All our blood specimens were collected at rather early time points after infection or vaccination, thus with time, a broader neutralizing capacity towards the heterologous variant might be observed due to somatic hypermutation and affinity maturation, although in the case of Omicron most likely will not restore neutralization loss [60]. Overall, we could show that responses to variants before Omicron were associated with reduced, but not complete loss in neutralization both by infection-derived as well as vaccine derived immu...

    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.
    • 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.

    About SciScore

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  4. Version published to 10.1101/2021.12.28.21268491v1 on medRxiv