The rapid implementation of SARS-CoV-2 vaccination is now a global health-care priority. Successful phase 3 trial outcomes have been reported for numerous vaccines that induce robust humoral and cellular immune responses against the SARS-CoV-2 spike protein. 1–6 To gain rapid control of accelerating cases and maximise public health impact, the UK Government has adopted the strategy of delaying second vaccination to 12 weeks. This policy has generated controversy, particularly among health-care workers (HCWs), the majority of whom have received BNT162b2 mRNA vaccine. 7 Limited data on immune responses to single-dose vaccination with BNT162b2 are available, and vaccine responses following previous natural infection have not been assessed in clinical trials. 2–6 We have therefore investigated immunological responses to single-dose BNT162b2 using a combination of serology, live virus neutralisation, and T-cell enzymelinked immunospot (ELISpot) assays. 72 HCWs from Imperial College Healthcare NHS Trust, who were vaccinated between Dec 23 and Dec 31, 2020, provided blood samples at the time of receiving their first dose of BNT162b2 vaccine and 21–25 days after vaccination. Baseline samples were tested for antibodies to SARS-CoV-2 nucleocapsid and spike (anti-S) proteins using the Abbott Architect SARS-CoV-2 IgG and IgG Quant II, respectively