CD4+ and CD8+ T cell and antibody correlates of protection against Delta vaccine breakthrough infection: A nested case-control study within the PITCH study
Neale, I.; Ali, M.; Kronsteiner, B.; Longet, S.; Abraham, P.; Deeks, A. S.; Brown, A.; Moore, S. C.; Stafford, L.; Dobson, S. L.; Plowright, M.; Newman, T. A. H.; Wu, M. Y.; Crick COVID Immunity Pipeline, ; Carr, E. J.; Beale, R.; Otter, A. D.; Hopkins, S.; Hall, V.; Tomic, A.; Payne, R. P.; Barnes, E.; Richter, A.; Duncan, C. J. A.; Turtle, L.; de Silva, T. I.; Carroll, M.; Lambe, T.; Klenerman, P.; Dunachie, S.; PITCH Consortium,
Show abstract
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. 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). 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 (IFN{gamma}) responses compared with controls. In a subset of matched cases and controls, cases had lower CD4+ and CD8+ IFN{gamma} and tumour necrosis factor responses to Delta S peptides with reduced CD8+ responses to Delta versus ancestral peptides compared with controls. Our findings support a protective role for T cells against Delta breakthrough infection.
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