Omicron BA.4/BA.5 escape neutralizing immunity elicited by BA.1 infection

  1. Khadija Khan
  2. Farina Karim
  3. Yashica Ganga
  4. Mallory Bernstein
  5. Zesuliwe Jule
  6. Kajal Reedoy
  7. Sandile Cele
  8. Gila Lustig
  9. Daniel Amoako
  10. Nicole Wolter
  11. Natasha Samsunder
  12. Aida Sivro
  13. James Emmanuel San
  14. Jennifer Giandhari
  15. Houriiyah Tegally
  16. Sureshnee Pillay
  17. Yeshnee Naidoo
  18. Matilda Mazibuko
  19. Yoliswa Miya
  20. Nokuthula Ngcobo
  21. Nithendra Manickchund
  22. Nombulelo Magula
  23. Quarraisha Abdool Karim
  24. Anne von Gottberg
  25. Salim S. Abdool Karim
  26. Willem Hanekom
  27. Bernadett I. Gosnell
  28. COMMIT-KZN Team
  29. Thandeka Khoza
  30. Theresa Smit
  31. Emily Wong
  32. Richard J. Lessells
  33. Tulio de Oliveira
  34. Mahomed-Yunus S. Moosa
  35. Alex Sigal

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Abstract

SARS-CoV-2 Omicron (B.1.1.529) BA.4 and BA.5 sub-lineages, first detected in South Africa, have changes relative to Omicron BA.1 including substitutions in the spike receptor binding domain. Here we isolated live BA.4 and BA.5 viruses and measured BA.4/BA.5 neutralization elicited by BA.1 infection either in the absence or presence of previous vaccination as well as from vaccination without BA.1 infection. In BA.1-infected unvaccinated individuals, neutralization relative to BA.1 declines 7.6-fold for BA.4 and 7.5-fold for BA.5. In vaccinated individuals with subsequent BA.1 infection, neutralization relative to BA.1 decreases 3.2-fold for BA.4 and 2.6-fold for BA.5. The fold-drop versus ancestral virus neutralization in this group is 4.0-fold for BA.1, 12.9-fold for BA.4, and 10.3-fold for BA.5. In contrast, BA.4/BA.5 escape is similar to BA.1 in the absence of BA.1 elicited immunity: fold-drop relative to ancestral virus neutralization is 19.8-fold for BA.1, 19.6-fold for BA.4, and 20.9-fold for BA.5. These results show considerable escape of BA.4/BA.5 from BA.1 elicited immunity which is moderated with vaccination and may indicate that BA.4/BA.5 may have the strongest selective advantage in evading neutralization relative to BA.1 in unvaccinated, BA.1 infected individuals.

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  1. Version published to 10.1038/s41467-022-32396-9
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    SciScore for 10.1101/2022.04.29.22274477: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Informed consent and ethical statement: Blood samples were obtained after written informed consent from adults with PCR-confirmed SARS-CoV-2 infection who were enrolled in a prospective cohort study at the Africa Health Research Institute approved by the Biomedical Research Ethics Committee at the University of KwaZulu–Natal (reference BREC/00001275/2020).
    IRB: Informed consent and ethical statement: Blood samples were obtained after written informed consent from adults with PCR-confirmed SARS-CoV-2 infection who were enrolled in a prospective cohort study at the Africa Health Research Institute approved by the Biomedical Research Ethics Committee at the University of KwaZulu–Natal (reference BREC/00001275/2020).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    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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  3. Version published to 10.1101/2022.04.29.22274477v1 on medRxiv