T-Cell and Antibody Responses to First BNT162b2 Vaccine Dose in Previously SARS-CoV-2-Infected and Infection-Naive UK Healthcare Workers: A Multicentre, Prospective, Observational Cohort Study

Background: Following a single dose of BNT162b2 mRNA vaccine, higher antibody titres are observed following prior SARS-CoV-2 infection than in infection-naive individuals, but T-cell responses are less well defined. Methods: We sampled healthcare workers (HCWs) enrolled in the UK PITCH study, before and after BNT162b2 mRNA vaccination. We measured spike-specific antibody, and quantified T-cell responses by IFNγ ELISpot assay and intracellular staining of peripheral blood mononuclear cells (PBMC), comparing SARS-CoV-2-naive individuals to those with prior infection. Findings: HCWs aged 22 to 71 years received one (n=216) or two (n=21) vaccine doses. After a single dose, the spike-specific T-cell response was six-fold higher in previously-infected vs. naive individuals (median 340 vs. 58 SFU/10 6 PBMC, p<0.0001; fresh PBMC, n=99). The T-cell response in previously-infected individuals after one vaccine dose was equivalent to naive individuals receiving two vaccine doses (median 158 vs. 165 SFU/10 6 PBMCs, p=0.65; cryopreserved PBMC, n=117). Anti-spike IgG levels following a single dose in those previously infected (median 512.9 antibody units/ml (AU/ml)) were 6.8-fold higher vs. naive individuals following one dose (median 75.0 AU/ml, p<0.0001) and 2.9-fold higher than naive individuals given two doses three weeks apart (179.9 AU/ml, p=0.03). Following vaccination, plasma from individuals with prior infection demonstrated higher in vitro neutralisation of the B.1.351 variant of concern compared to naive individuals. Interpretation: Following a single BNT162b2 dose, HCWs with a prior history of SARS-CoV-2 infection have significantly higher T-cell and antibody responses than naive individuals. Funding: UK Department of Health and Social Care and UK Coronavirus Immunology Consortium. Declaration of Interests: None to declare. Ethics Approval Statement: PITCH was recognised as a sub-study of SIREN on 2 December 2020, which was approved by the Berkshire Research Ethics Committee, Health Research 250 Authority (IRAS ID 284460, REC reference 20/SC/0230). Some participants were recruited under aligned REC-approved study protocols (Appendix). The study was conducted in compliance with the principles of the Declaration of Helsinki (2008) and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines.