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SARS-CoV-2 elicits robust adaptive immune responses regardless of disease severity

BACKGROUND: The SARS-CoV-2 pandemic currently prevails worldwide. To understand the immunological signature of SARS-CoV-2 infections and aid the search and evaluation of new treatment modalities and vaccines, comprehensive characterization of adaptive immune responses towards SARS-CoV-2 is needed. M...

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Autores principales: Nielsen, Stine SF, Vibholm, Line K, Monrad, Ida, Olesen, Rikke, Frattari, Giacomo S, Pahus, Marie H, Højen, Jesper F, Gunst, Jesper D, Erikstrup, Christian, Holleufer, Andreas, Hartmann, Rune, Østergaard, Lars, Søgaard, Ole S, Schleimann, Mariane H, Tolstrup, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176920/
https://www.ncbi.nlm.nih.gov/pubmed/34098342
http://dx.doi.org/10.1016/j.ebiom.2021.103410
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author Nielsen, Stine SF
Vibholm, Line K
Monrad, Ida
Olesen, Rikke
Frattari, Giacomo S
Pahus, Marie H
Højen, Jesper F
Gunst, Jesper D
Erikstrup, Christian
Holleufer, Andreas
Hartmann, Rune
Østergaard, Lars
Søgaard, Ole S
Schleimann, Mariane H
Tolstrup, Martin
author_facet Nielsen, Stine SF
Vibholm, Line K
Monrad, Ida
Olesen, Rikke
Frattari, Giacomo S
Pahus, Marie H
Højen, Jesper F
Gunst, Jesper D
Erikstrup, Christian
Holleufer, Andreas
Hartmann, Rune
Østergaard, Lars
Søgaard, Ole S
Schleimann, Mariane H
Tolstrup, Martin
author_sort Nielsen, Stine SF
collection PubMed
description BACKGROUND: The SARS-CoV-2 pandemic currently prevails worldwide. To understand the immunological signature of SARS-CoV-2 infections and aid the search and evaluation of new treatment modalities and vaccines, comprehensive characterization of adaptive immune responses towards SARS-CoV-2 is needed. METHODS: We included 203 recovered SARS-CoV-2 infected patients in Denmark between April 3(rd) and July 9(th) 2020, at least 14 days after COVID-19 symptom recovery. The participants had experienced a range of disease severities from asymptomatic to severe. We collected plasma, serum and PBMC's for analysis of SARS-CoV-2 specific antibody response by Meso Scale analysis including other coronavirus strains, ACE2 competition, IgA ELISA, pseudovirus neutralization capacity, and dextramer flow cytometry analysis of CD8(+) T cells. The immunological outcomes were compared amongst severity groups within the cohort, and 10 pre-pandemic SARS-CoV-2 negative controls. FINDINGS: We report broad serological profiles within the cohort, detecting antibody binding to other human coronaviruses. 202(>99%) participants had SARS-CoV-2 specific antibodies, with SARS-CoV-2 neutralization and spike-ACE2 receptor interaction blocking observed in 193(95%) individuals. A significant positive correlation (r=0.7804) between spike-ACE2 blocking antibody titers and neutralization potency was observed. Further, SARS-CoV-2 specific CD8(+) T-cell responses were clear and quantifiable in 95 of 106(90%) HLA-A2(+) individuals. INTERPRETATION: The viral surface spike protein was identified as the dominant target for both neutralizing antibodies and CD8(+) T-cell responses. Overall, the majority of patients had robust adaptive immune responses, regardless of their disease severity. FUNDING: This study was supported by the Danish Ministry for Research and Education (grant# 0238-00001B) and The Danish Innovation Fund (grant# 0208-00018B)
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spelling pubmed-81769202021-06-04 SARS-CoV-2 elicits robust adaptive immune responses regardless of disease severity Nielsen, Stine SF Vibholm, Line K Monrad, Ida Olesen, Rikke Frattari, Giacomo S Pahus, Marie H Højen, Jesper F Gunst, Jesper D Erikstrup, Christian Holleufer, Andreas Hartmann, Rune Østergaard, Lars Søgaard, Ole S Schleimann, Mariane H Tolstrup, Martin EBioMedicine Research Paper BACKGROUND: The SARS-CoV-2 pandemic currently prevails worldwide. To understand the immunological signature of SARS-CoV-2 infections and aid the search and evaluation of new treatment modalities and vaccines, comprehensive characterization of adaptive immune responses towards SARS-CoV-2 is needed. METHODS: We included 203 recovered SARS-CoV-2 infected patients in Denmark between April 3(rd) and July 9(th) 2020, at least 14 days after COVID-19 symptom recovery. The participants had experienced a range of disease severities from asymptomatic to severe. We collected plasma, serum and PBMC's for analysis of SARS-CoV-2 specific antibody response by Meso Scale analysis including other coronavirus strains, ACE2 competition, IgA ELISA, pseudovirus neutralization capacity, and dextramer flow cytometry analysis of CD8(+) T cells. The immunological outcomes were compared amongst severity groups within the cohort, and 10 pre-pandemic SARS-CoV-2 negative controls. FINDINGS: We report broad serological profiles within the cohort, detecting antibody binding to other human coronaviruses. 202(>99%) participants had SARS-CoV-2 specific antibodies, with SARS-CoV-2 neutralization and spike-ACE2 receptor interaction blocking observed in 193(95%) individuals. A significant positive correlation (r=0.7804) between spike-ACE2 blocking antibody titers and neutralization potency was observed. Further, SARS-CoV-2 specific CD8(+) T-cell responses were clear and quantifiable in 95 of 106(90%) HLA-A2(+) individuals. INTERPRETATION: The viral surface spike protein was identified as the dominant target for both neutralizing antibodies and CD8(+) T-cell responses. Overall, the majority of patients had robust adaptive immune responses, regardless of their disease severity. FUNDING: This study was supported by the Danish Ministry for Research and Education (grant# 0238-00001B) and The Danish Innovation Fund (grant# 0208-00018B) Elsevier 2021-06-04 /pmc/articles/PMC8176920/ /pubmed/34098342 http://dx.doi.org/10.1016/j.ebiom.2021.103410 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Nielsen, Stine SF
Vibholm, Line K
Monrad, Ida
Olesen, Rikke
Frattari, Giacomo S
Pahus, Marie H
Højen, Jesper F
Gunst, Jesper D
Erikstrup, Christian
Holleufer, Andreas
Hartmann, Rune
Østergaard, Lars
Søgaard, Ole S
Schleimann, Mariane H
Tolstrup, Martin
SARS-CoV-2 elicits robust adaptive immune responses regardless of disease severity
title SARS-CoV-2 elicits robust adaptive immune responses regardless of disease severity
title_full SARS-CoV-2 elicits robust adaptive immune responses regardless of disease severity
title_fullStr SARS-CoV-2 elicits robust adaptive immune responses regardless of disease severity
title_full_unstemmed SARS-CoV-2 elicits robust adaptive immune responses regardless of disease severity
title_short SARS-CoV-2 elicits robust adaptive immune responses regardless of disease severity
title_sort sars-cov-2 elicits robust adaptive immune responses regardless of disease severity
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176920/
https://www.ncbi.nlm.nih.gov/pubmed/34098342
http://dx.doi.org/10.1016/j.ebiom.2021.103410
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