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

10.1126/science.abh1282

Science

25th June 2021

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:

Affiliations

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: r.boyton@imperial.ac.uk

↵† 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.

Authors

Catherine J. Reynolds^{1 †}, Corinna Pade^{2 †}, Joseph M. Gibbons^{2 †}, David K. Butler¹, Ashley D. Otter³ , Katia Menacho⁴ , Marianna Fontana^5,6, 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 Manisty^4,9, Thomas A. Treibel^4,9, James C. Moon^4,9, UK COVIDsortium Investigators‡, Ana M. Valdes^10,11, Áine McKnight²§, Daniel M. Altmann¹²§, Rosemary Boyton^1,13§*