Abstract
Omicron has become the globally dominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, creating additional challenges due to its ability to evade neutralization. Here, we report that neutralizing antibodies against Omicron variants are undetected following COVID-19 infection with ancestral or past SARS-CoV-2 variant viruses or after two-dose mRNA vaccination. Compared with two-dose vaccination, a three-dose vaccination course induces broad neutralizing antibody responses with improved durability against different SARS-CoV-2 variants, although neutralizing antibody titers against Omicron remain low. Intriguingly, among individuals with three-dose vaccination, Omicron breakthrough infection substantially augments serum neutralizing activity against a broad spectrum of SARS-CoV-2 variants, including Omicron variants BA.1, BA.2, and BA.5. Additionally, after Omicron breakthrough infection, memory T cells respond to the spike proteins of both ancestral and Omicron SARS-CoV-2 by producing cytokines with polyfunctionality. These results suggest that Omicron breakthrough infection following three-dose mRNA vaccination induces pan-SARS-CoV-2 immunity that may protect against emerging SARS-CoV-2 variants of concern.
Original language | English |
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Article number | 100764 |
Journal | Cell Reports Medicine |
Volume | 3 |
Issue number | 10 |
DOIs | |
Publication status | Published - 2022 Oct 18 |
Bibliographical note
Funding Information:We thank the study participants and coworkers at the Laboratory Medicine, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine at NMC. We thank B. Judd and P. Kretchmer for proofreading the article. This work was supported by the Institute for Basic Science (IBS), Korea (IBS-R801-D1 and IBS-R801-D2); National Medical Center (grant no. NMC2020-MS-02); Korea National Institute of Health; and Korea Disease Control and Prevention Agency (2021ER260300). This work was also financially supported by the Research Year of Chungbuk National University in 2021 for H.W.J. Conceptualization, H.W.J. J.Y.S. E.-C.S. and Y.K.C.; methodology, H.W.J. S.-M.K. M.K.J. J.-S.Y. E.-H.K. S.-G.J. and J.G.; investigation, H.W.J. S.-M.K. M.K.J. J.Y.N. J.-S.Y. E.-H.K. Y.-I.K. S.-G.J. J.G. M.A.C. R.R. J.H.C. H.-S.K. J.H.K. J.U. C.K. J.-S.P. Y.K. B.S.C. S.J. J.Y.C. K.-H.S. Y.-D.K. J.Y.S. E.-C.S. and Y.K.C.; visualization, H.W.J. S.-M.K. M.K.J. and J.-S.Y.; funding acquisition, E.-C.S. Y.K.C. J.Y.S. and J.-S.P.; writing – original draft, H.W.J. S.-M.K. M.K.J. J.-S.Y. E.-C.S. and Y.K.C.; writing – review & editing, H.W.J. S.-M.K. M.K.J. J.Y.N. J.-S.Y. J.Y.S. E.-C.S. and Y.K.C. The authors declare no competing interests. We worked to ensure gender balance and to ensure ethnic or other types of diversity in the recruitment of human subjects. While citing references scientifically relevant for this work, we also actively worked to promote gender balance in our reference list.
Funding Information:
We thank the study participants and coworkers at the Laboratory Medicine, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine at NMC. We thank B. Judd and P. Kretchmer for proofreading the article. This work was supported by the Institute for Basic Science ( IBS ), Korea ( IBS-R801-D1 and IBS-R801-D2 ); National Medical Center (grant no. NMC2020-MS-02 ); Korea National Institute of Health ; and Korea Disease Control and Prevention Agency ( 2021ER260300 ). This work was also financially supported by the Research Year of Chungbuk National University in 2021 for H.W.J.
Publisher Copyright:
© 2022 The Author(s)
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)