Breakthrough SARS-COV-2 infection induces broad anti-viral T cell immunity
Katie Eireann Lineburg,
Pauline Crooks,
Jyothy Raju,
Laetitia Le Texier,
Panteha Khaledi,
Kiana Berry,
Srividhya Swaminathan,
Archana Panikkar,
Sweera Rehan,
Kristyan Guppy-Coles,
Michelle Anne Neller,
Rajiv Khanna,
Corey Smith
Affiliations
Katie Eireann Lineburg
QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Infection and Inflammation Program, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia
Pauline Crooks
QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Infection and Inflammation Program, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia
Jyothy Raju
QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Infection and Inflammation Program, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia
Laetitia Le Texier
QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Infection and Inflammation Program, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia
Panteha Khaledi
QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Infection and Inflammation Program, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia
Kiana Berry
QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Infection and Inflammation Program, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia; Faculty of Medicine, The University of Queensland, Herston, QLD 4006, Australia
Srividhya Swaminathan
QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Infection and Inflammation Program, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia; Faculty of Medicine, The University of Queensland, Herston, QLD 4006, Australia
Archana Panikkar
QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Infection and Inflammation Program, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia
Sweera Rehan
QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Infection and Inflammation Program, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia
Kristyan Guppy-Coles
Cardiology, Royal Brisbane and Women’s Hospital, Metro North Hospital and Health Services, Queensland Health, QLD 4006, Australia
Michelle Anne Neller
QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Infection and Inflammation Program, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia
Rajiv Khanna
QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Infection and Inflammation Program, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia
Corey Smith
QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Infection and Inflammation Program, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia; Faculty of Medicine, The University of Queensland, Herston, QLD 4006, Australia; Corresponding author
Summary: Vaccines have curtailed the devastation wrought by COVID-19. Nevertheless, emerging variants result in a high incidence of breakthrough infections. Here we assess the impact of vaccination and breakthrough infection on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) T cell immunity. We demonstrate that COVID-19 vaccination induces robust spike-specific T cell responses that, within the CD4+ compartment, display comparable IFN-γ responses to SARS-CoV-2 infection without vaccination. Vaccine-induced CD8+ IFN-γ responses however, were significantly greater than those primed by SARS-CoV-2 infection alone. This increased responsiveness is associated with induction of novel HLA-restricted CD8+ T cell epitopes not primed by infection alone (without vaccination). Despite these augmented responses, breakthrough infection still induced de novo T cell responses against additional SARS-CoV-2 CD8+ epitopes that display HLA-associated immunodominance hierarchies consistent with those in unvaccinated COVID-19 convalescent individuals. This study demonstrates the unique modulation of anti-viral T cell responses against multiple viral antigens following consecutive yet distinct priming events in COVID-19 vaccination and breakthrough infection.
