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.


Neale, Isabel, Ali, Mohammad, Kronsteiner, Barbara, Longet, Stephanie, Abraham, Priyanka, Deeks, Alexandra S, Brown, Anthony, Moore, Shona C ORCID: 0000-0001-8610-2806, Stafford, Lizzie, Dobson, Susan L ORCID: 0000-0002-4958-0021 et al (show 21 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-e0121223.

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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 (<i>n</i> = 32), while controls were those who did not report a positive test or undergo anti-nucleocapsid immunoglobulin G (IgG) seroconversion during this period (<i>n</i> = 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. IMPORTANCE Defining correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine breakthrough infection informs vaccine policy for booster doses and future vaccine designs. Existing studies demonstrate humoral correlates of protection, but the role of T cells in protection is still unclear. In this study, we explore antibody and T cell immune responses associated with protection against Delta variant vaccine breakthrough infection in a well-characterized cohort of UK Healthcare Workers (HCWs). We demonstrate evidence to support a role for CD4+ and CD8+ T cells as well as antibodies against Delta vaccine breakthrough infection. In addition, our results suggest a potential role for cross-reactive T cells in vaccine breakthrough.

Item Type: Article
Uncontrolled Keywords: Crick COVID Immunity Pipeline, PITCH Consortium
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 03 Oct 2023 08:37
Last Modified: 13 Nov 2023 03:08
DOI: 10.1128/mbio.01212-23
Open Access URL: http://doi.org/10.1128/mbio.01212-23
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3173343
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