is funded by an NIHR Global Research Professorship (NIHR300791). This work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (CC2230, CC2087), the UK Medical Research Council (CC2230, CC2087), and the Wellcome Trust (CC2230, CC2087). This work was funded by the United Kingdom Department of Health and Social Care as part of the PITCH (Protective Immunity from T cells to COVID-19 in Healthcare Workers) Consortium, UKRI as part of "Investigation of proven vaccine breakthrough by SARS-CoV-2 variants in established UK healthcare worker cohorts: SIREN consortium & PITCH Plus Pathway" (MR/W02067X/1), with contributions from UKRI/NIHR through the UK Coronavirus Immunology Consortium (UK-CIC), the Huo Family Foundation and The National Institute for Health Research (UKRIDHSC COVID-19 Rapid Response Rolling Call, Grant Reference Number COV19-RECPLAS). All other authors have declared no competing interests.
Oxford University has entered a joint COVID-19 vaccine development partnership with AstraZeneca. is a Scientific Advisor to the Scottish Parliament on COVID-19 for which she receives a fee. Our findings support a protective role for T cells against Delta breakthrough infection. In a subset of matched cases and controls, cases had lower CD4+ and CD8+ IFNγ and tumour necrosis factor responses to Delta S peptides with reduced CD8+ responses to Delta versus ancestral peptides compared with controls. 28 days after second vaccination, before all breakthroughs occurred, cases had lower ancestral S- and RBD-specific immunoglobulin G titres and S1- and S2-specific T cell interferon gamma (IFNγ) responses compared with controls. We studied 279 volunteers in the Protective Immunity from T Cells in Healthcare Workers (PITCH) UK study, including 32 cases (with SARS-CoV-2 positive testing after two vaccine doses during the Delta-dominant era) and 247 controls (no positive test nor anti-nucleocapsid seroconversion during this period). T cell correlates of protection against SARS-CoV-2 infection after vaccination (‘vaccine breakthrough’) are incompletely defined, especially the specific contributions of CD4+ and CD8+ T cells.
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