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Exposed seronegative: Cellular immune responses to SARS-CoV-2 in the absence of seroconversion

The factors determining whether infection will occur following exposure to SARS-CoV-2 remain elusive. Certain SARS-CoV-2-exposed individuals mount a specific T-cell response but fail to seroconvert, representing a population that may provide further clarity on the nature of infection susceptibility...

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Autores principales: Jay, Cecilia, Ratcliff, Jeremy, Turtle, Lance, Goulder, Philip, Klenerman, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9909393/
https://www.ncbi.nlm.nih.gov/pubmed/36776841
http://dx.doi.org/10.3389/fimmu.2023.1092910
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author Jay, Cecilia
Ratcliff, Jeremy
Turtle, Lance
Goulder, Philip
Klenerman, Paul
author_facet Jay, Cecilia
Ratcliff, Jeremy
Turtle, Lance
Goulder, Philip
Klenerman, Paul
author_sort Jay, Cecilia
collection PubMed
description The factors determining whether infection will occur following exposure to SARS-CoV-2 remain elusive. Certain SARS-CoV-2-exposed individuals mount a specific T-cell response but fail to seroconvert, representing a population that may provide further clarity on the nature of infection susceptibility and correlates of protection against SARS-CoV-2. Exposed seronegative individuals have been reported in patients exposed to the blood-borne pathogens Human Immunodeficiency virus and Hepatitis C virus and the sexually transmitted viruses Hepatitis B virus and Herpes Simplex virus. By comparing the quality of seronegative T-cell responses to SARS-CoV-2 with seronegative cellular immunity to these highly divergent viruses, common patterns emerge that offer insights on the role of cellular immunity against infection. For both SARS-CoV-2 and Hepatitis C, T-cell responses in exposed seronegatives are consistently higher than in unexposed individuals, but lower than in infected, seropositive patients. Durability of T-cell responses to Hepatitis C is dependent upon repeated exposure to antigen – single exposures do not generate long-lived memory T-cells. Finally, exposure to SARS-CoV-2 induces varying degrees of immune activation, suggesting that exposed seronegative individuals represent points on a spectrum rather than a discrete group. Together, these findings paint a complex landscape of the nature of infection but provide clues as to what may be protective early on in SARS-CoV-2 disease course. Further research on this phenomenon, particularly through cohort studies, is warranted.
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spelling pubmed-99093932023-02-10 Exposed seronegative: Cellular immune responses to SARS-CoV-2 in the absence of seroconversion Jay, Cecilia Ratcliff, Jeremy Turtle, Lance Goulder, Philip Klenerman, Paul Front Immunol Immunology The factors determining whether infection will occur following exposure to SARS-CoV-2 remain elusive. Certain SARS-CoV-2-exposed individuals mount a specific T-cell response but fail to seroconvert, representing a population that may provide further clarity on the nature of infection susceptibility and correlates of protection against SARS-CoV-2. Exposed seronegative individuals have been reported in patients exposed to the blood-borne pathogens Human Immunodeficiency virus and Hepatitis C virus and the sexually transmitted viruses Hepatitis B virus and Herpes Simplex virus. By comparing the quality of seronegative T-cell responses to SARS-CoV-2 with seronegative cellular immunity to these highly divergent viruses, common patterns emerge that offer insights on the role of cellular immunity against infection. For both SARS-CoV-2 and Hepatitis C, T-cell responses in exposed seronegatives are consistently higher than in unexposed individuals, but lower than in infected, seropositive patients. Durability of T-cell responses to Hepatitis C is dependent upon repeated exposure to antigen – single exposures do not generate long-lived memory T-cells. Finally, exposure to SARS-CoV-2 induces varying degrees of immune activation, suggesting that exposed seronegative individuals represent points on a spectrum rather than a discrete group. Together, these findings paint a complex landscape of the nature of infection but provide clues as to what may be protective early on in SARS-CoV-2 disease course. Further research on this phenomenon, particularly through cohort studies, is warranted. Frontiers Media S.A. 2023-01-26 /pmc/articles/PMC9909393/ /pubmed/36776841 http://dx.doi.org/10.3389/fimmu.2023.1092910 Text en Copyright © 2023 Jay, Ratcliff, Turtle, Goulder and Klenerman https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Jay, Cecilia
Ratcliff, Jeremy
Turtle, Lance
Goulder, Philip
Klenerman, Paul
Exposed seronegative: Cellular immune responses to SARS-CoV-2 in the absence of seroconversion
title Exposed seronegative: Cellular immune responses to SARS-CoV-2 in the absence of seroconversion
title_full Exposed seronegative: Cellular immune responses to SARS-CoV-2 in the absence of seroconversion
title_fullStr Exposed seronegative: Cellular immune responses to SARS-CoV-2 in the absence of seroconversion
title_full_unstemmed Exposed seronegative: Cellular immune responses to SARS-CoV-2 in the absence of seroconversion
title_short Exposed seronegative: Cellular immune responses to SARS-CoV-2 in the absence of seroconversion
title_sort exposed seronegative: cellular immune responses to sars-cov-2 in the absence of seroconversion
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9909393/
https://www.ncbi.nlm.nih.gov/pubmed/36776841
http://dx.doi.org/10.3389/fimmu.2023.1092910
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