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, 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
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.
Conflict of interest statement
Declaration of interests C.Y.C. is the director of the UCSF-Abbott Viral Diagnostics and Discovery and receives research support for SARS-CoV-2 studies from Abbott Laboratories. The other authors declare no competing interests.
Copyright © 2022 Elsevier Inc. All rights reserved.
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