Nature Communications (Aug 2023)
Omicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history
- Hailey Hornsby,
- Alexander R. Nicols,
- Stephanie Longet,
- Chang Liu,
- Adriana Tomic,
- Adrienn Angyal,
- Barbara Kronsteiner,
- Jessica K. Tyerman,
- Tom Tipton,
- Peijun Zhang,
- Marta Gallis,
- Piyada Supasa,
- Muneeswaran Selvaraj,
- Priyanka Abraham,
- Isabel Neale,
- Mohammad Ali,
- Natalie A. Barratt,
- Jeremy M. Nell,
- Lotta Gustafsson,
- Scarlett Strickland,
- Irina Grouneva,
- Timothy Rostron,
- Shona C. Moore,
- Luisa M. Hering,
- Susan L. Dobson,
- Sagida Bibi,
- Juthathip Mongkolsapaya,
- Teresa Lambe,
- Dan Wootton,
- Victoria Hall,
- Susan Hopkins,
- Tao Dong,
- Eleanor Barnes,
- Gavin Screaton,
- The PITCH Consortium,
- Alex Richter,
- Lance Turtle,
- Sarah L. Rowland-Jones,
- Miles Carroll,
- Christopher J. A. Duncan,
- Paul Klenerman,
- Susanna J. Dunachie,
- Rebecca P. Payne,
- Thushan I. de Silva
Affiliations
- Hailey Hornsby
- Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield
- Alexander R. Nicols
- Translational and Clinical Research Institute, Immunity, and Inflammation Theme, Newcastle University
- Stephanie Longet
- Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford
- Chang Liu
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford
- Adriana Tomic
- National Emerging Infectious Diseases Laboratories, Boston University
- Adrienn Angyal
- Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield
- Barbara Kronsteiner
- Peter Medawar Building for Pathogen Research, Nuffield Dept. of Clinical Medicine, University of Oxford
- Jessica K. Tyerman
- Translational and Clinical Research Institute, Immunity, and Inflammation Theme, Newcastle University
- Tom Tipton
- Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford
- Peijun Zhang
- Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield
- Marta Gallis
- Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield
- Piyada Supasa
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford
- Muneeswaran Selvaraj
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford
- Priyanka Abraham
- Peter Medawar Building for Pathogen Research, Nuffield Dept. of Clinical Medicine, University of Oxford
- Isabel Neale
- Peter Medawar Building for Pathogen Research, Nuffield Dept. of Clinical Medicine, University of Oxford
- Mohammad Ali
- Peter Medawar Building for Pathogen Research, Nuffield Dept. of Clinical Medicine, University of Oxford
- Natalie A. Barratt
- Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield
- Jeremy M. Nell
- Translational and Clinical Research Institute, Immunity, and Inflammation Theme, Newcastle University
- Lotta Gustafsson
- Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield
- Scarlett Strickland
- Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield
- Irina Grouneva
- Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield
- Timothy Rostron
- MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Shona C. Moore
- NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool
- Luisa M. Hering
- NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool
- Susan L. Dobson
- NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool
- Sagida Bibi
- Oxford Vaccine Group, Department of Paediatrics, University of Oxford
- Juthathip Mongkolsapaya
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford
- Teresa Lambe
- Oxford Vaccine Group, Department of Paediatrics, University of Oxford
- Dan Wootton
- NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool
- Victoria Hall
- UK Health Security Agency
- Susan Hopkins
- UK Health Security Agency
- Tao Dong
- MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Eleanor Barnes
- Nuffield Department of Medicine, University of Oxford
- Gavin Screaton
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford
- The PITCH Consortium
- Alex Richter
- Institute for Immunology and Immunotherapy, College of Medical and Dental Science, University of Birmingham
- Lance Turtle
- NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool
- Sarah L. Rowland-Jones
- Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield
- Miles Carroll
- Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford
- Christopher J. A. Duncan
- Translational and Clinical Research Institute, Immunity, and Inflammation Theme, Newcastle University
- Paul Klenerman
- Peter Medawar Building for Pathogen Research, Nuffield Dept. of Clinical Medicine, University of Oxford
- Susanna J. Dunachie
- Peter Medawar Building for Pathogen Research, Nuffield Dept. of Clinical Medicine, University of Oxford
- Rebecca P. Payne
- Translational and Clinical Research Institute, Immunity, and Inflammation Theme, Newcastle University
- Thushan I. de Silva
- Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield
- DOI
- https://doi.org/10.1038/s41467-023-40592-4
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 16
Abstract
Abstract Pronounced immune escape by the SARS-CoV-2 Omicron variant has resulted in many individuals possessing hybrid immunity, generated through a combination of vaccination and infection. Concerns have been raised that omicron breakthrough infections in triple-vaccinated individuals result in poor induction of omicron-specific immunity, and that prior SARS-CoV-2 infection is associated with immune dampening. Taking a broad and comprehensive approach, we characterize mucosal and blood immunity to spike and non-spike antigens following BA.1/BA.2 infections in triple mRNA-vaccinated individuals, with and without prior SARS-CoV-2 infection. We find that most individuals increase BA.1/BA.2/BA.5-specific neutralizing antibodies following infection, but confirm that the magnitude of increase and post-omicron titres are higher in the infection-naive. In contrast, significant increases in nasal responses, including neutralizing activity against BA.5 spike, are seen regardless of infection history. Spike-specific T cells increase only in infection-naive vaccinees; however, post-omicron T cell responses are significantly higher in the previously-infected, who display a maximally induced response with a highly cytotoxic CD8+ phenotype following their 3rd mRNA vaccine dose. Responses to non-spike antigens increase significantly regardless of prior infection status. These findings suggest that hybrid immunity induced by omicron breakthrough infections is characterized by significant immune enhancement that can help protect against future omicron variants.
