BA.2 and BA.5 omicron differ immunologically from both BA.1 omicron and pre-omicron variants

  1. Annika Rössler
  2. Antonia Netzl
  3. Ludwig Knabl
  4. Helena Schäfer
  5. Samuel H. Wilks
  6. David Bante
  7. Barbara Falkensammer
  8. Wegene Borena
  9. Dorothee von Laer
  10. Derek J. Smith
  11. Janine Kimpel

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Abstract

Several studies have shown that SARS-CoV-2 BA.1 omicron is an immune escape variant. Meanwhile, however, omicron BA.2 and BA.5 became dominant in many countries and replaced BA.1. As both have several mutations compared to BA.1, we analyzed whether BA.2 and BA.5 show further immune escape relative to BA.1. Here, we characterized neutralization profiles against the BA.2 and BA.5 omicron sub-variants in plasma samples from individuals with different history of exposures to infection/vaccination and found that unvaccinated individuals after a single exposure to BA.2 had limited cross-neutralizing antibodies to pre-omicron variants and to BA.1. Consequently, our antigenic map including all Variants of Concern and BA.1, BA.2 and BA.5 omicron sub-variants, showed that all omicron sub-variants are distinct to pre-omicron variants, but that the three omicron variants are also antigenically distinct from each other. The antibody landscapes illustrate that cross-neutralizing antibodies against the current antigenic space, as described in our maps, are generated only after three or more exposures to antigenically close variants but also after two exposures to antigenically distant variants. Here, we describe the antigenic space inhabited by the relevant SARS-CoV-2 variants, the understanding of which will have important implications for further vaccine strain adaptations.

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  1. Version published to 10.1038/s41467-022-35312-3
  2. ScreenIT

    SciScore for 10.1101/2022.05.10.22274906: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethics statement: The ethics committee (EC) of the Medical University of Innsbruck has approved the study with EC numbers: 1100/2020, 1111/2020, 1330/2020, 1064/2021, 1093/2021, 1168/2021, 1191/2021, and 1197/2021.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Viruses were grown on Vero cells stably overexpressing TMPRSS2 and ACE2.
    Vero
    suggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)
    Software and Algorithms
    SentencesResources
    1,19 Continuous 50% neutralization titers were calculated in GraphPad Prism 9.0.1
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    (GraphPad Software, Inc., La Jolla, CA, USA) using a non-linear regression.
    GraphPad
    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:
    One limitation of our study is that most samples were collected shortly after infection and therefore we could not analyze longevity of cross-neutralizing antibodies. However, others also found improved levels and durability of cross-neutralizing antibodies after three or more exposures (vaccination or infection).3,8,27 In a non-human primate model, titers of cross-neutralizing antibodies were similarly increased by either a third dose of a wild type-specific mRNA vaccine or a beta-specific mRNA vaccine after two doses of a wild type-specific mRNA vaccine.28 We propose three hypotheses for the improved cross-neutralization after repeated exposure even for non-exposed variants. Firstly, this could be a consequence of antibody saturation against the encountered virus variants while the reactivity against unencountered viruses could still be boosted with overall increasing antibody titers, resulting in smaller differences in neutralization between exposed and unexposed variants with overall increased antibody titers. Secondly, the prior encounter of two different pre-omicron variants could boost immunity against conserved epitopes shared with the two omicron sub-lineages. Some monoclonal antibodies have been shown to retain activity against BA.1 and/or BA.2 omicron.29 Thirdly, the broad polyclonality of the response after exposure to two different variants might contribute to omicron neutralization, as a cocktail of monoclonal antibodies was reported to improve neutralization of...

    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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  3. Version published to 10.1101/2022.05.10.22274906v1 on medRxiv