Distinct antigenic properties of the SARS-CoV-2 Omicron lineages BA.4 and BA.5

  1. Brian J. Willett
  2. Ashwini Kurshan
  3. Nazia Thakur
  4. Joseph Newman
  5. Maria Manali
  6. Grace Tyson
  7. Nicola Logan
  8. Pablo R. Murcia
  9. Luke B. Snell
  10. Jonathan D. Edgeworth
  11. Jie Zhou
  12. Ksenia Sukhova
  13. Gayatri Amirthalingam
  14. Kevin Brown
  15. Bryan Charleston
  16. Michael H. Malim
  17. Emma C. Thomson
  18. Wendy S. Barclay
  19. Dalan Bailey
  20. Katie J. Doores
  21. Thomas P. Peacock

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Abstract

Over the course of the pandemic variants have arisen at a steady rate. The most recent variants to emerge, BA.4 and BA.5, form part of the Omicron lineage and were first found in Southern Africa where they are driving the current wave of infection.

In this report, we perform an in-depth characterisation of the antigenicity of the BA.4/BA.5 Spike protein by comparing sera collected post-vaccination, post-BA.1 or BA.2 infection, or post breakthrough infection of vaccinated individuals with the Omicron variant. In addition, we assess sensitivity to neutralisation by commonly used therapeutic monoclonal antibodies.

We find sera collected post-vaccination have a similar ability to neutralise BA.1, BA.2 and BA.4/BA.5. In contrast, in the absence of vaccination, prior infection with BA.2 or, in particular, BA.1 results in an antibody response that neutralises BA.4/BA.5 poorly. Breakthrough infection with Omicron in vaccinees leads to a broad neutralising response against the new variants. The sensitivity of BA.4/BA.5 to neutralisation by therapeutic monoclonal antibodies was similar to that of BA.2.

These data suggest BA.4/BA.5 are antigenically distinct from BA.1 and, to a lesser extent, BA.2. The enhanced breadth of neutralisation observed following breakthrough infection with Omicron suggests that vaccination with heterologous or multivalent antigens may represent viable strategies for the development of cross-neutralising antibody responses.

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  1. ScreenIT

    SciScore for 10.1101/2022.05.25.493397: (What is this?)

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

    Table 1: Rigor

    EthicsField Sample Permit: Antisera and ethics: Hamster antisera was generated as we have described previously7, and was carried out under a United Kingdom Home Office License, P48DAD9B4.
    Consent: All DOVE participants gave informed consent to take part in the study, which was approved by the North-West Liverpool Central Research Ethics Committee (REC reference 21/NW/0073).
    IRB: All DOVE participants gave informed consent to take part in the study, which was approved by the North-West Liverpool Central Research Ethics Committee (REC reference 21/NW/0073).
    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
    Briefly, HEK 293T cells were transfected with lentiviral packaging plasmids and the named Spike construct - D614G(WT), BA.1, BA.2 or BA.4/5 to produce
    HEK 293T
    suggested: None
    Sera was then combined with target cells expressing human ACE2 (HEK293T or HeLa) and incubated for 48-72 hours.
    HeLa
    suggested: None

    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.
    • 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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  2. Version published to 10.1101/2022.05.25.493397v1 on bioRxiv