Cellular immunity to SARS-CoV-2 following intrafamilial exposure in seronegative family members

Frontiers in Immunology

Immunology

Nicholas Lim¹  Anna Csala¹  Philip Goulder¹  Emily Adland¹  Owen B. Spiller²  Lucy C. Jones²  Lance Turtle³  Donal Skelly⁴  Carl-Philipp Hackstein⁵  Lizzie Stafford⁵  Craig P. Thompson⁵  Chris Conlon⁵  Ane Ogbe⁵  Matthew Edmans⁵  Cecilia Jay⁵  Anni Jamsen⁵  Ellie Barnes⁶  Susanna Dunachie⁶  Paul Klenerman⁶  Miles Carroll⁶  Christina Dold⁷  Oliver Sampson⁸  Stephanie Longet⁹ 

[1] Department of Paediatrics, University of Oxford, Oxford, United Kingdom;Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom;Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom;Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom;Oxford University Hospitals, University of Oxford, Oxford, United Kingdom;Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom;Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom;National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre, Oxford University Hospitals National Health Service (NHS) Foundation Trust, Oxford, United Kingdom;Oxford Vaccine Group, University of Oxford, Oxford, United Kingdom;Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom;Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom;

关键词: SARS-CoV-2;    COVID-19;    exposed seronegative;    family;    T-cells;   

DOI  :  10.3389/fimmu.2023.1248658

 received in 2023-06-27, accepted in 2023-08-11,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionFamily studies of antiviral immunity provide an opportunity to assess virus-specific immunity in infected and highly exposed individuals, as well as to examine the dynamics of viral infection within families. Transmission of SARS-CoV-2 between family members represented a major route for viral spread during the early stages of the pandemic, due to the nature of SARS-CoV-2 transmission through close contacts.MethodsHere, humoral and cellular immunity is explored in 264 SARS-CoV-2 infected, exposed or unexposed individuals from 81 families in the United Kingdom sampled in the winter of 2020 before widespread vaccination and infection.ResultsWe describe robust cellular and humoral immunity into COVID-19 convalescence, albeit with marked heterogeneity between families and between individuals. T-cell response magnitude is associated with male sex and older age by multiple linear regression. SARS-CoV-2-specific T-cell responses in seronegative individuals are widespread, particularly in adults and in individuals exposed to SARS-CoV-2 through an infected family member. The magnitude of this response is associated with the number of seropositive family members, with a greater number of seropositive individuals within a family leading to stronger T-cell immunity in seronegative individuals.DiscussionThese results support a model whereby exposure to SARS-CoV-2 promotes T-cell immunity in the absence of an antibody response. The source of these seronegative T-cell responses to SARS-CoV-2 has been suggested as cross-reactive immunity to endemic coronaviruses that is expanded upon SARS-CoV-2 exposure. However, in this study, no association between HCoV-specific immunity and seronegative T-cell immunity to SARS-CoV-2 is identified, suggesting that de novo T-cell immunity may be generated in seronegative SARS-CoV-2 exposed individuals.

【 授权许可】

Unknown   
Copyright © 2023 Jay, Adland, Csala, Dold, Edmans, Hackstein, Jamsen, Lim, Longet, Ogbe, Sampson, Skelly, Spiller, Stafford, Thompson, Turtle, Barnes, Dunachie, Carroll, Klenerman, Conlon, Goulder and Jones