Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants

Venice Servellita; Abdullah M Syed; Mary Kate Morris; Noah Brazer; Prachi Saldhi; Miguel Garcia-Knight; Bharath Sreekumar; Mir M Khalid; Alison Ciling; Pei-Yi Chen; G Renuka Kumar; Amelia S Gliwa; Jenny Nguyen; Alicia Sotomayor-Gonzalez; Yueyuan Zhang; Edwin Frias; John Prostko; John Hackett Jr; Raul Andino; Debra A Wadford; Carl Hanson; Jennifer Doudna; Melanie Ott; Charles Y Chiu

doi:10.1016/j.cell.2022.03.019

Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants

Cell. 2022 Apr 28;185(9):1539-1548.e5. doi: 10.1016/j.cell.2022.03.019. Epub 2022 Mar 18.

Authors

Venice Servellita¹, Abdullah M Syed², Mary Kate Morris³, Noah Brazer¹, Prachi Saldhi¹, Miguel Garcia-Knight⁴, Bharath Sreekumar⁵, Mir M Khalid⁵, Alison Ciling², Pei-Yi Chen⁵, G Renuka Kumar⁵, Amelia S Gliwa¹, Jenny Nguyen¹, Alicia Sotomayor-Gonzalez¹, Yueyuan Zhang¹, Edwin Frias⁶, John Prostko⁶, John Hackett Jr⁶, Raul Andino⁴, Debra A Wadford³, Carl Hanson⁷, Jennifer Doudna⁸, Melanie Ott⁹, Charles Y Chiu¹⁰

Affiliations

¹ Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA; UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA.
² Gladstone Institute of Data Science and Biotechnology, San Francisco, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
³ Viral and Rickettsial Disease Laboratory, California Department of Public Health, Richmond, CA, USA.
⁴ Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
⁵ Gladstone Institutes, San Francisco, CA, USA.
⁶ Abbott Laboratories, Abbott Park, IL, USA.
⁷ Viral and Rickettsial Disease Laboratory, California Department of Public Health, Richmond, CA, USA. Electronic address: carl.hanson@cdph.ca.gov.
⁸ Gladstone Institute of Data Science and Biotechnology, San Francisco, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA, USA; Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA. Electronic address: doudna@berkeley.edu.
⁹ California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA, USA; Gladstone Institutes, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: melanie.ott@gladstone.ucsf.edu.
¹⁰ Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA; UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA; Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: charles.chiu@ucsf.edu.

Abstract

Virus-like particle (VLP) and live virus assays were used to investigate neutralizing immunity against Delta and Omicron SARS-CoV-2 variants in 259 samples from 128 vaccinated individuals. Following Delta breakthrough infection, titers against WT rose 57-fold and 3.1-fold compared with uninfected boosted and unboosted individuals, respectively, versus only a 5.8-fold increase and 3.1-fold decrease for Omicron breakthrough infection. Among immunocompetent, unboosted patients, Delta breakthrough infections induced 10.8-fold higher titers against WT compared with Omicron (p = 0.037). Decreased antibody responses in Omicron breakthrough infections relative to Delta were potentially related to a higher proportion of asymptomatic or mild breakthrough infections (55.0% versus 28.6%, respectively), which exhibited 12.3-fold lower titers against WT compared with moderate to severe infections (p = 0.020). Following either Delta or Omicron breakthrough infection, limited variant-specific cross-neutralizing immunity was observed. These results suggest that Omicron breakthrough infections are less immunogenic than Delta, thus providing reduced protection against reinfection or infection from future variants.

Keywords: B.1.1.529; B.1.617.2; COVID-19; Delta variant; Omicron variant; SARS-CoV-2; VLP; antibody neutralization; boosted breakthrough infection; breakthrough infection; humoral immunity; pseudovirus infectivity studies; quantitative antibody assay; variant of concern; variant severity; virus-like particle.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Research Support, N.I.H., Extramural

MeSH terms

Antibodies, Neutralizing
Antibodies, Viral
BNT162 Vaccine
COVID-19 Vaccines
COVID-19* / immunology
COVID-19* / prevention & control
Humans
SARS-CoV-2*

Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants

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