Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783703329582350336 |
---|---|
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) |
format | Online Article Text |
id | pubmed-8176920 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT nielsenstinesf sarscov2elicitsrobustadaptiveimmuneresponsesregardlessofdiseaseseverity AT vibholmlinek sarscov2elicitsrobustadaptiveimmuneresponsesregardlessofdiseaseseverity AT monradida sarscov2elicitsrobustadaptiveimmuneresponsesregardlessofdiseaseseverity AT olesenrikke sarscov2elicitsrobustadaptiveimmuneresponsesregardlessofdiseaseseverity AT frattarigiacomos sarscov2elicitsrobustadaptiveimmuneresponsesregardlessofdiseaseseverity AT pahusmarieh sarscov2elicitsrobustadaptiveimmuneresponsesregardlessofdiseaseseverity AT højenjesperf sarscov2elicitsrobustadaptiveimmuneresponsesregardlessofdiseaseseverity AT gunstjesperd sarscov2elicitsrobustadaptiveimmuneresponsesregardlessofdiseaseseverity AT erikstrupchristian sarscov2elicitsrobustadaptiveimmuneresponsesregardlessofdiseaseseverity AT holleuferandreas sarscov2elicitsrobustadaptiveimmuneresponsesregardlessofdiseaseseverity AT hartmannrune sarscov2elicitsrobustadaptiveimmuneresponsesregardlessofdiseaseseverity AT østergaardlars sarscov2elicitsrobustadaptiveimmuneresponsesregardlessofdiseaseseverity AT søgaardoles sarscov2elicitsrobustadaptiveimmuneresponsesregardlessofdiseaseseverity AT schleimannmarianeh sarscov2elicitsrobustadaptiveimmuneresponsesregardlessofdiseaseseverity AT tolstrupmartin sarscov2elicitsrobustadaptiveimmuneresponsesregardlessofdiseaseseverity |