SARS-CoV-2 Variant Exposures Elicit Antibody Responses With Differential Cross-Neutralization of Established and Emerging Strains Including Delta and Omicron

  1. Matthew T Laurie
  2. Jamin Liu
  3. Sara Sunshine
  4. James Peng
  5. Douglas Black
  6. Anthea M Mitchell
  7. Sabrina A Mann
  8. Genay Pilarowski
  9. Kelsey C Zorn
  10. Luis Rubio
  11. Sara Bravo
  12. Carina Marquez
  13. Joseph J Sabatino
  14. Kristen Mittl
  15. Maya Petersen
  16. Diane Havlir
  17. Joseph DeRisi

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Abstract

The wide spectrum of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with phenotypes impacting transmission and antibody sensitivity necessitates investigation of immune responses to different spike protein versions. Here, we compare neutralization of variants of concern, including B.1.617.2 (delta) and B.1.1.529 (omicron), in sera from individuals exposed to variant infection, vaccination, or both. We demonstrate that neutralizing antibody responses are strongest against variants sharing certain spike mutations with the immunizing exposure, and exposure to multiple spike variants increases breadth of variant cross-neutralization. These findings contribute to understanding relationships between exposures and antibody responses and may inform booster vaccination strategies.

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  1. Version published to 10.1093/infdis/jiab635
  2. ScreenIT

    SciScore for 10.1101/2021.09.08.21263095: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Serum collection: Samples for laboratory studies were obtained under informed consent from participants in an ongoing community based, SARS-CoV-2 testing, genomic surveillance, and vaccination program “Unidos en Salud”, which serves a predominantly Latino community in the Mission neighborhood in San Francisco, California [8,9].
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line AuthenticationContamination: Cells were verified to be free of mycoplasma contamination with the MycoAlert Mycoplasma detection kit (Lonza).

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Pseudoviruses were titered on Huh7.5.1 cells overexpressing ACE2 and TMPRSS2 (gift of Andreas Puschnik) using GFP expression to measure the concentration of focus forming units (ffu) [13].
    Huh7.5.1
    suggested: RRID:CVCL_E049)
    Pseudovirus neutralization experiments: Huh7.5.1-ACE2-TMPRSS2 cells were seeded in 96-well plates at a density of 7000 cells/well one day prior to pseudovirus inoculation.
    Huh7.5.1-ACE2-TMPRSS2
    suggested: None
    Software and Algorithms
    SentencesResources
    Data analysis: Pseudovirus flow cytometry data was analyzed with FlowJo to determine the percentage of GFP-positive cells, indicating pseudovirus transduction.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Neutralization titers (NT50 and NT90) were calculated from eight-point response curves generated in GraphPad Prism 7 using four-parameter logistic regression.
    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:
    A limitation of this study is the relatively small number of serum samples, however the shift in neutralization titer between D614G and variant pseudoviruses shows strong consistency between samples. These serology data leverage human exposures to an array of naturally occurring spike mutations, including those relevant to B.1.617.2, providing a real-world complement to previous animal studies investigating heterologous boosting or multivalent vaccination strategies [14,15]. Together, these results contribute additional evidence suggesting that heterologous boosting strategies may be an important and effective measure to address newly emergent variants with the potential to evade existing acquired immunity. Future studies investigating immune responses to additional emerging variants in vaccinated and unvaccinated individuals will contribute to identifying spike antigen versions that elicit broadly neutralizing antibody responses.

    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

    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.

  3. Version published to 10.1101/2021.09.08.21263095 on medRxiv