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Limited cross-variant immunity from SARS-CoV-2 Omicron without vaccination - Nature.com

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Abstract

SARS-CoV-2 Delta and Omicron are globally relevant variants of concern (VOCs). While individuals infected with Delta are at risk to develop severe lung disease, infection with Omicron often causes milder symptoms, especially in vaccinated individuals1,2. The question arises whether widespread Omicron infections could lead to future cross-variant protection, accelerating the end of the pandemic. Here we show that without vaccination, infection with Omicron induces a limited humoral immune response in mice and humans. Sera from mice overexpressing the human ACE2 receptor and infected with Omicron neutralize only Omicron, but no other VOCs, whereas broader cross-variant neutralization was observed after WA1 and Delta infections. Unlike WA1 and Delta, Omicron replicates to low levels in the lungs and brains of infected animals, leading to mild disease with reduced pro-inflammatory cytokine expression and diminished activation of lung-resident T cells. Sera from unvaccinated, Omicron-infected individuals show the same limited neutralization of only Omicron itself. In contrast, Omicron breakthrough infections induce overall higher neutralization titers against all VOCs. Our results demonstrate that Omicron infection enhances preexisting immunity elicited by vaccines but, on its own, may not confer broad protection against non-Omicron variants in unvaccinated individuals.

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Author notes

  1. These authors contributed equally: Rahul K. Suryawanshi, Irene P. Chen and Tongcui Ma

Affiliations

  1. Gladstone Institutes, San Francisco, CA, USA

    Rahul K. Suryawanshi, Irene P. Chen, Tongcui Ma, Abdullah M. Syed, Camille R. Simoneau, Alison Ciling, Mir M. Khalid, Bharath Sreekumar, Pei-Yi Chen, G. Renuka Kumar, Mauricio Montano, Ronne Gascon, Chia-Lin Tsou, Frank W. Soveg, Ashley F. George, Warner C. Greene, Nadia R. Roan, Jennifer A. Doudna & Melanie Ott

  2. Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, CA, USA

    Irene P. Chen

  3. Department of Medicine, University of California San Francisco, San Francisco, CA, USA

    Irene P. Chen, Camille R. Simoneau, Warner C. Greene, Charles Y. Chiu & Melanie Ott

  4. Quantitative Biosciences Institute COVID-19 Research Group, University of California San Francisco, San Francisco, CA, USA

    Irene P. Chen, Camille R. Simoneau & Melanie Ott

  5. UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA

    Tongcui Ma & Charles Y. Chiu

  6. Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA

    Abdullah M. Syed, Alison Ciling, Charles Y. Chiu & Jennifer A. Doudna

  7. Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA

    Noah Brazer, Prachi Saldhi, Alicia Sotomayor-Gonzalez, Venice Servellita, Amelia Gliwa, Jenny Nguyen & Charles Y. Chiu

  8. Michael Hulton Center for HIV Cure Research at Gladstone, San Francisco, CA, USA

    Mauricio Montano & Warner C. Greene

  9. Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA

    Miguel A. Garcia-Knight, Warner C. Greene & Raul Andino

  10. Curative Inc., 430 S Cataract Ave, San Dimas, CA, USA

    Ines Silva, Bilal Milbes, Noah Kojima, Victoria Hess, Maria Shacreaw, Lauren Lopez, Matthew Brobeck, Fred Turner & Lee Spraggon

  11. Department of Urology, University of California, San Francisco, San Francisco, USA

    Ashley F. George & Nadia R. Roan

  12. Department of Medicine and Department of Anesthesia, Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA

    Xiaohui Fang, Mazharul Maishan & Michael Matthay

  13. California Department of Public Health, Richmond, CA, USA

    Mary Kate Morris, Debra Wadford & Carl Hanson

  14. Chan Zuckerberg Biohub, San Francisco, CA, USA

    Charles Y. Chiu & Melanie Ott

  15. Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA

    Jennifer A. Doudna

  16. Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA

    Jennifer A. Doudna

  17. Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA, USA

    Jennifer A. Doudna

  18. Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA

    Jennifer A. Doudna

  19. California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, USA

    Jennifer A. Doudna

Authors
  1. Rahul K. Suryawanshi
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  2. Irene P. Chen
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  3. Tongcui Ma
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  4. Abdullah M. Syed
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  5. Noah Brazer
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  6. Prachi Saldhi
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  7. Camille R. Simoneau
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  8. Alison Ciling
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  9. Mir M. Khalid
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  10. Bharath Sreekumar
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  11. Pei-Yi Chen
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  12. G. Renuka Kumar
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  13. Mauricio Montano
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  14. Ronne Gascon
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  15. Chia-Lin Tsou
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  16. Miguel A. Garcia-Knight
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  17. Alicia Sotomayor-Gonzalez
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  18. Venice Servellita
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  19. Amelia Gliwa
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  20. Jenny Nguyen
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  21. Ines Silva
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  22. Bilal Milbes
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  23. Noah Kojima
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  24. Victoria Hess
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  25. Maria Shacreaw
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  26. Lauren Lopez
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  27. Matthew Brobeck
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  28. Fred Turner
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  29. Frank W. Soveg
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  30. Ashley F. George
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  31. Xiaohui Fang
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  32. Mazharul Maishan
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  33. Michael Matthay
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  34. Mary Kate Morris
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  35. Debra Wadford
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  36. Carl Hanson
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  37. Warner C. Greene
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  38. Raul Andino
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  39. Lee Spraggon
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  40. Nadia R. Roan
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  41. Charles Y. Chiu
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  42. Jennifer A. Doudna
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  43. Melanie Ott
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Corresponding authors

Correspondence to Nadia R. Roan, Charles Y. Chiu, Jennifer A. Doudna or Melanie Ott.

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Suryawanshi, R.K., Chen, I.P., Ma, T. et al. Limited cross-variant immunity from SARS-CoV-2 Omicron without vaccination. Nature (2022). https://ift.tt/7KmwnvL

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