SARS-CoV-2 evolved during advanced HIV disease immunosuppression has Beta-like escape of vaccine and Delta infection elicited immunity

  1. Sandile Cele
  2. Farina Karim
  3. Gila Lustig
  4. James Emmanuel San
  5. Tandile Hermanus
  6. Houriiyah Tegally
  7. Jumari Snyman
  8. Thandeka Moyo-Gwete
  9. Eduan Wilkinson
  10. Mallory Bernstein
  11. Khadija Khan
  12. Shi-Hsia Hwa
  13. Sasha W. Tilles
  14. Lavanya Singh
  15. Jennifer Giandhari
  16. Ntombifuthi Mthabela
  17. Matilda Mazibuko
  18. Yashica Ganga
  19. Bernadett I. Gosnell
  20. Salim Abdool Karim
  21. Willem Hanekom
  22. Wesley C. Van Voorhis
  23. Thumbi Ndung’u
  24. COMMIT-KZN Team
  25. Richard J. Lessells
  26. Penny L. Moore
  27. Mahomed-Yunus S. Moosa
  28. Tulio de Oliveira
  29. Alex Sigal
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Abstract

Characterizing SARS-CoV-2 evolution in specific geographies may help predict the properties of variants coming from these regions. We mapped neutralization of a SARS-CoV-2 strain that evolved over 6 months from the ancestral virus in a person with advanced HIV disease. Infection was before the emergence of the Beta variant first identified in South Africa, and the Delta variant. We compared early and late evolved virus to the ancestral, Beta, Alpha, and Delta viruses and tested against convalescent plasma from ancestral, Beta, and Delta infections. Early virus was similar to ancestral, whereas late virus was similar to Beta, exhibiting vaccine escape and, despite pre-dating Delta, strong escape of Delta-elicited neutralization. This example is consistent with the notion that variants arising in immune-compromised hosts, including those with advanced HIV disease, may evolve immune escape of vaccines and enhanced escape of Delta immunity, with implications for vaccine breakthrough and reinfections.

Highlights

  • A prolonged ancestral SARS-CoV-2 infection pre-dating the emergence of Beta and Delta resulted in evolution of a Beta-like serological phenotype

  • Serological phenotype includes strong escape from Delta infection elicited immunity, intermediate escape from ancestral virus immunity, and weak escape from Beta immunity

  • Evolved virus showed substantial but incomplete escape from antibodies elicited by BNT162b2 vaccination

Graphical abstract

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