Neale, I. orcid.org/0000-0001-7026-7390, Ali, M. orcid.org/0000-0003-0170-7182, Kronsteiner, B. orcid.org/0000-0003-0867-2867 et al. (26 more authors) (2023) CD4+ and CD8+ T cells and antibodies are associated with protection against Delta vaccine breakthrough infection: a nested case-control study within the PITCH study. mBio, 14 (5). e0121223. ISSN 2161-2129
Abstract
Serological correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after vaccination (“vaccine breakthrough”) have been described. However, T cell correlates of protection against breakthrough are incompletely defined, especially the specific contributions of CD4+ and CD8+ T cells. Here, 279 volunteers in the Protective Immunity from T Cells in Healthcare Workers (PITCH) UK cohort study were enrolled in a nested case-control study. Cases were those who tested SARS-CoV-2 PCR or lateral flow device (LFD) positive after two vaccine doses during the Delta-predominant era (n = 32), while controls were those who did not report a positive test or undergo anti-nucleocapsid immunoglobulin G (IgG) seroconversion during this period (n = 247). Previous SARS-CoV-2 infection prior to vaccination was associated with reduced odds of vaccine breakthrough. Using samples from 28 d after the second vaccine dose, before all breakthroughs occurred, we observed future cases had lower ancestral spike (S)- and receptor binding domain-specific IgG titers and S1- and S2-specific T cell interferon gamma (IFNγ) responses compared with controls, although these differences did not persist when individuals were stratified according to previous infection status before vaccination. In a subset of matched infection-naïve cases and controls, vaccine breakthrough cases had lower CD4+ and CD8+ IFNγ and tumor necrosis factor (TNF) responses to Delta S peptides compared with controls. For CD8+ responses, this difference appeared to be driven by reduced responses to Delta compared with ancestral peptides among cases; this reduced response to Delta peptides was not observed in controls. Our findings support a protective role for T cells against Delta breakthrough infection.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Editors: |
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Copyright, Publisher and Additional Information: | © 2023 Neale et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. https://creativecommons.org/licenses/by/4.0/ |
Keywords: | COVID vaccine; COVID-19; Delta; SARS-CoV-2; T cells; antibody; immunity; vaccine breakthrough; Humans; Case-Control Studies; Breakthrough Infections; Antibodies; CD8-Positive T-Lymphocytes; SARS-CoV-2; Vaccines; CD4-Positive T-Lymphocytes; Antibodies, Viral; Antibodies, Neutralizing |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health |
Funding Information: | Funder Grant number BRITISH HEART FOUNDATION FS/18/52/33808 British Heart Foundation PG/11/116/29288 WELLCOME TRUST (THE) 110058/A/15/Z MEDICAL RESEARCH COUNCIL MR/W02067X/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 09 Jan 2024 08:37 |
Last Modified: | 09 Jan 2024 08:37 |
Status: | Published |
Publisher: | American Society for Microbiology |
Refereed: | Yes |
Identification Number: | 10.1128/mbio.01212-23 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:207279 |