Prior SARS-CoV-2 infection rescues B and T cell responses to variants after first vaccine dose



Contributing to research themes:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine rollout has coincided with the spread of variants of concern. We investigated whether single-dose vaccination, with or without prior infection, confers cross-protective immunity to variants. We analyzed T and B cell responses after first-dose vaccination with the Pfizer/BioNTech messenger RNA vaccine BNT162b2 in health care workers (HCW) followed longitudinally, with or without prior Wuhan-Hu-1 SARS-CoV-2 infection. After one dose, individuals with prior infection showed enhanced T cell immunity, antibody-secreting memory B cell response to the spike protein, and neutralizing antibodies effective against variants B.1.1.7 and B.1.351. By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 and B.1.351 spike mutations resulted in increased, abrogated, or unchanged T cell responses, depending on human leukocyte antigen (HLA) polymorphisms. Single-dose vaccination with BNT162b2 in the context of prior infection with a heterologous variant substantially enhances neutralizing antibody responses against variants.

Author list:


1Department of Infectious Disease, Imperial College London, London, UK.

2Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

3National Infection Service, Public Health England, Porton Down, UK.

4St Bartholomew’s Hospital, Barts Health NHS Trust, London, UK.

5Royal Free London NHS Foundation Trust, London, UK.

6Division of Medicine, University College London, London, UK.

7James Wigg Practice, Kentish Town, London, UK.

8Division of Infection and Immunity, University College London, London, UK.

9Institute of Cardiovascular Science, University College London, London, UK.

10Academic Rheumatology, Clinical Sciences, Nottingham City Hospital, Nottingham, UK.

11NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK.

12Department of Immunology and Inflammation, Imperial College London, London, UK.

13Lung Division, Royal Brompton and Harefield Hospitals, London, UK.

*Corresponding author: Email:


† These authors contributed equally to this work.

§ These authors contributed equally to this work.

‡ UK COVIDsortium Investigators and UK COVIDsortium Immune Correlates Network collaborators and affiliations are listed in the supplementary materials.



Catherine J. Reynolds1 †, Corinna Pade2 †, Joseph M. Gibbons2 †, David K. Butler1 , Ashley D. Otter3 , Katia Menacho4 , Marianna Fontana5,6, Angelique Smit5 , Jane E. Sackville-West7 , Teresa Cutino-Moguel4 , Mala K. Maini8 , Benjamin Chain8 , Mahdad Noursadeghi8 , UK COVIDsortium Immune Correlates Network‡, Tim Brooks3 , Amanda Semper3 , Charlotte Manisty4,9, Thomas A. Treibel4,9, James C. Moon4,9, UK COVIDsortium Investigators‡, Ana M. Valdes10,11, Áine McKnight2 §, Daniel M. Altmann12§, Rosemary Boyton1,13§*