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Publications

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Epublish 31 citations

PubMed: 37604803 DOI: 10.1038/s41467-023-40592-4

Omicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history.

Nat Commun 14(1):5065

Authors: 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, 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

  • Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield, Sheffield, UK.
  • Translational and Clinical Research Institute, Immunity, and Inflammation Theme, Newcastle University, Newcastle, UK.
  • Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
  • Department of Microbiology, Boston University School of Medicine, Boston, MA, USA.
  • Department of Biomedical Engineering, Boston University, Boston, MA, USA.
  • Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Peter Medawar Building for Pathogen Research, Nuffield Dept. of Clinical Medicine, University of Oxford, Oxford, UK.
  • NDM Centre For Global Health Research, Nuffield Dept. of Clinical Medicine, University of Oxford, Oxford, UK.
  • Department of Infection and Tropical Medicine, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
  • Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
  • MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
  • Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
  • Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
  • Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
  • UK Health Security Agency, London, UK.
  • Faculty of Medicine, Department of Infectious Disease, Imperial College London, London, UK.
  • NIHR Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance, University of Oxford, Oxford, UK.
  • Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Oxford NIHR Biomedical Research Centre and Oxford University NHS Foundation Trust, Oxford, UK.
  • Institute for Immunology and Immunotherapy, College of Medical and Dental Science, University of Birmingham, Birmingham, UK.
  • University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
  • Tropical & Infectious Disease Unit, Liverpool University Hospitals NHS Foundation Trust (member of Liverpool Health Partners), Liverpool, UK.
  • Peter Medawar Building for Pathogen Research, Nuffield Dept. of Clinical Medicine, University of Oxford, Oxford, UK.
  • Oxford NIHR Biomedical Research Centre and Oxford University NHS Foundation Trust, Oxford, UK.
  • Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
  • Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
  • Division of Clinical Medicine, School of Medicine and Population Health, The University of Sheffield, Sheffield, UK.
  • Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
  • Vaccines and Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, The Gambia.

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 3 rd 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.

MeSH

Cells, Vaccines, Biological Science Disciplines, Vaccination, Immunity, History, Infections, Breakthrough Infections

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