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Article ; Online: Neutrophil-derived extracellular vesicles modulate the phenotype of naïve human neutrophils.

Amjadi, Maya F / Avner, Benjamin S / Greenlee-Wacker, Mallary C / Horswill, Alexander R / Nauseef, William M

2021 Volume 110, Issue 5, Page(s) 917–925

Abstract: Neutrophils (PMN) regulate inflammation in many ways, including communication with other immune cells via extracellular vesicles (EVs). EVs released by human neutrophils activated with N-formylmethionyl-leucyl-phenylalanine (fMLF) (PMN-fMLF EVs) had an ... ...

Abstract	Neutrophils (PMN) regulate inflammation in many ways, including communication with other immune cells via extracellular vesicles (EVs). EVs released by human neutrophils activated with N-formylmethionyl-leucyl-phenylalanine (fMLF) (PMN-fMLF EVs) had an outside-out orientation and contained functionally important neutrophil plasma membrane proteins, including flavocytochrome b558, and enzymatically active granule proteins, elastase, and myeloperoxidase. Treatment of naïve PMN with PMN-fMLF EVs primed fMLF-stimulated NADPH oxidase activity, increased surface expression of the complement receptors CD11b/CD18 and CD35, the specific granule membrane protein CD66, and flavocytochrome b
MeSH term(s)	Extracellular Vesicles/immunology ; Extracellular Vesicles/metabolism ; Humans ; NADPH Oxidases/metabolism ; Neutrophils/immunology ; Neutrophils/metabolism ; Phagocytosis/immunology ; Phenotype
Chemical Substances	NADPH Oxidases (EC 1.6.3.-)
Language	English
Publishing date	2021-03-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	605722-6
ISSN	1938-3673 ; 0741-5400
ISSN (online)	1938-3673
ISSN	0741-5400
DOI	10.1002/JLB.3AB0520-339RR
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Zs.A 603: Show issues

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Article ; Online: Novel and unique rheumatoid factors cross-react with viral epitopes in COVID-19.

Amjadi, Maya F / Parker, Maxwell H / Adyniec, Ryan R / Zheng, Zihao / Robbins, Alex M / Bashar, S Janna / Denny, Michael F / McCoy, Sara S / Ong, Irene M / Shelef, Miriam A

Journal of autoimmunity

2023 Volume 142, Page(s) 103132

Abstract: Rheumatoid factors (RFs), polyreactive antibodies canonically known to bind two conformational epitopes of IgG Fc, are a hallmark of rheumatoid arthritis but also can arise in other inflammatory conditions and infections. Also, infections may contribute ... ...

Abstract	Rheumatoid factors (RFs), polyreactive antibodies canonically known to bind two conformational epitopes of IgG Fc, are a hallmark of rheumatoid arthritis but also can arise in other inflammatory conditions and infections. Also, infections may contribute to the development of rheumatoid arthritis and other autoimmune diseases. Recently, RFs only in rheumatoid arthritis were found to bind novel linear IgG epitopes as well as thousands of other rheumatoid arthritis autoantigens. Specific epitopes recognized by infection-induced polyreactive RFs remain undefined but could provide insights into loss of immune tolerance. Here, we identified novel linear IgG epitopes bound by RFs in COVID-19 but not rheumatoid arthritis or other conditions. The main COVID-19 RF was polyreactive, binding two IgG and multiple viral peptides with a tripeptide motif, as well as IgG Fc and SARS-CoV-2 spike proteins. In contrast, a rheumatoid arthritis-specific RF recognized IgG Fc, but not tripeptide motif-containing peptides or spike. Thus, RFs have disease-specific IgG reactivity and distinct polyreactivities that reflect the broader immune response. Moreover, the polyreactivity of a virus-induced RF appears to be attributable to a very short peptide motif. These findings refine our understanding of RFs and provide new insights into how viral infections may contribute to autoimmunity.
MeSH term(s)	Humans ; Epitopes ; COVID-19 ; SARS-CoV-2 ; Rheumatoid Factor/metabolism ; Arthritis, Rheumatoid ; Autoimmune Diseases ; Peptides ; Immunoglobulin G
Chemical Substances	Epitopes ; Rheumatoid Factor (9009-79-4) ; Peptides ; Immunoglobulin G
Language	English
Publishing date	2023-11-11
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	639452-8
ISSN	1095-9157 ; 0896-8411
ISSN (online)	1095-9157
ISSN	0896-8411
DOI	10.1016/j.jaut.2023.103132
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Zs.A 2368: Show issues

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Article ; Online: Rheumatoid Factor and Anti-Modified Protein Antibody Reactivities Converge on IgG Epitopes.

Mergaert, Aisha M / Zheng, Zihao / Denny, Michael F / Amjadi, Maya F / Bashar, S Janna / Newton, Michael A / Malmström, Vivianne / Grönwall, Caroline / McCoy, Sara S / Shelef, Miriam A

Arthritis & rheumatology (Hoboken, N.J.)

2022 Volume 74, Issue 6, Page(s) 984–991

Abstract: Objective: Rheumatoid arthritis (RA) patients often develop rheumatoid factors (RFs), antibodies that bind IgG Fc, and anti-modified protein antibodies (AMPAs), multireactive autoantibodies that commonly bind citrullinated, homocitrullinated, and ... ...

Abstract	Objective: Rheumatoid arthritis (RA) patients often develop rheumatoid factors (RFs), antibodies that bind IgG Fc, and anti-modified protein antibodies (AMPAs), multireactive autoantibodies that commonly bind citrullinated, homocitrullinated, and acetylated antigens. Recently, antibodies that bind citrulline-containing IgG epitopes were discovered in RA, suggesting that additional undiscovered IgG epitopes could exist and that IgG could be a shared antigen for RFs and AMPAs. This study was undertaken to reveal new IgG epitopes in rheumatic disease and to determine if multireactive AMPAs bind IgG. Methods: Using sera from patients with RA, systemic lupus erythematosus, Sjögren's disease (SjD), or spondyloarthropathy, IgG binding to native, citrulline-containing, and homocitrulline-containing linear epitopes of the IgG constant region was evaluated by peptide array, with highly bound epitopes further evaluated by enzyme-linked immunosorbent assay (ELISA). Binding of monoclonal AMPAs to IgG-derived peptides and IgG Fc was also evaluated by ELISA. Results: Seropositive RA sera showed high IgG binding to multiple citrulline- and homocitrulline-containing IgG-derived peptides, whereas anti-SSA+ sera from SjD patients showed consistent binding to a single linear native epitope of IgG in the hinge region. Monoclonal AMPAs bound citrulline- and homocitrulline-containing IgG peptides and modified IgG Fc. Conclusion: The repertoire of epitopes bound by AMPAs includes modified IgG epitopes, positioning IgG as a common antigen that connects the otherwise divergent reactivities of RFs and AMPAs.
MeSH term(s)	Arthritis, Rheumatoid ; Autoantibodies ; Citrulline ; Epitopes ; Humans ; Immunoglobulin G ; Peptides ; Rheumatoid Factor ; Sjogren's Syndrome
Chemical Substances	Autoantibodies ; Epitopes ; Immunoglobulin G ; Peptides ; Citrulline (29VT07BGDA) ; Rheumatoid Factor (9009-79-4)
Language	English
Publishing date	2022-04-10
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2756371-6
ISSN	2326-5205 ; 2326-5191
ISSN (online)	2326-5205
ISSN	2326-5191
DOI	10.1002/art.42064
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Zs.A 24: Show issues

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Article ; Online: Anti-membrane Antibodies Persist at Least One Year and Discriminate Between Past Coronavirus Disease 2019 Infection and Vaccination.

Amjadi, Maya F / Adyniec, Ryan R / Gupta, Srishti / Bashar, S Janna / Mergaert, Aisha M / Braun, Katarina M / Moreno, Gage K / O'Connor, David H / Friedrich, Thomas C / Safdar, Nasia / McCoy, Sara S / Shelef, Miriam A

The Journal of infectious diseases

2022 Volume 226, Issue 11, Page(s) 1897–1902

Abstract: Background: The consequences of past coronavirus disease 2019 (COVID-19) infection for personal and population health are emerging, but accurately identifying distant infection is a challenge. Anti-spike antibodies rise after both vaccination and ... ...

Abstract	Background: The consequences of past coronavirus disease 2019 (COVID-19) infection for personal and population health are emerging, but accurately identifying distant infection is a challenge. Anti-spike antibodies rise after both vaccination and infection and anti-nucleocapsid antibodies rapidly decline. Methods: We evaluated anti-membrane antibodies in COVID-19 naive, vaccinated, and convalescent subjects to determine if they persist and accurately detect distant infection. Results: We found that anti-membrane antibodies persist for at least 1 year and are a sensitive and specific marker of past COVID-19 infection. Conclusions: Thus, anti-membrane and anti-spike antibodies together can differentiate between COVID-19 convalescent, vaccinated, and naive states to advance public health and research.
MeSH term(s)	Humans ; COVID-19/diagnosis ; Vaccination ; Public Health ; Virion ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus
Chemical Substances	Antibodies, Viral ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2022-06-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiac263
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Uh II Zs.50: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 445: Show issues

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Article: Anti-membrane and anti-spike antibodies are long-lasting and together discriminate between past COVID-19 infection and vaccination.

medRxiv : the preprint server for health sciences

2021

Abstract: The consequences of past COVID-19 infection for personal health and long-term population immunity are only starting to be revealed. Unfortunately, detecting past infection is currently a challenge, limiting clinical and research endeavors. Widely ... ...

Abstract	The consequences of past COVID-19 infection for personal health and long-term population immunity are only starting to be revealed. Unfortunately, detecting past infection is currently a challenge, limiting clinical and research endeavors. Widely available anti-SARS-CoV-2 antibody tests cannot differentiate between past infection and vaccination given vaccine-induced anti-spike antibodies and the rapid loss of infection-induced anti-nucleocapsid antibodies. Anti-membrane antibodies develop after COVID-19, but their long-term persistence is unknown. Here, we demonstrate that anti-membrane IgG is a sensitive and specific marker of past COVID-19 infection and persists at least one year. We also confirm that anti-receptor binding domain (RBD) Ig is a long-lasting, sensitive, and specific marker of past infection and vaccination, while anti-nucleocapsid IgG lacks specificity and quickly declines after COVID-19. Thus, a combination of anti-membrane and anti-RBD antibodies can accurately differentiate between distant COVID-19 infection, vaccination, and naïve states to advance public health, individual healthcare, and research goals.
Language	English
Publishing date	2021-11-08
Publishing country	United States
Document type	Preprint
DOI	10.1101/2021.11.02.21265750
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Article: The landscape of antibody binding in SARS-CoV-2 infection.

Heffron, Anna S / McIlwain, Sean J / Amjadi, Maya F / Baker, David A / Khullar, Saniya / Sethi, Ajay K / Palmenberg, Ann C / Shelef, Miriam A / O'Connor, David H / Ong, Irene M

bioRxiv : the preprint server for biology

2021

Abstract: The search for potential antibody-based diagnostics, vaccines, and therapeutics for pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has focused almost exclusively on the spike (S) and nucleocapsid (N) proteins. Coronavirus membrane ( ...

Abstract	The search for potential antibody-based diagnostics, vaccines, and therapeutics for pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has focused almost exclusively on the spike (S) and nucleocapsid (N) proteins. Coronavirus membrane (M), ORF3a, and ORF8 proteins are humoral immunogens in other coronaviruses (CoVs) but remain largely uninvestigated for SARS-CoV-2. Here we use ultradense peptide microarray mapping to show that SARS-CoV-2 infection induces robust antibody responses to epitopes throughout the SARS-CoV-2 proteome, particularly in M, in which one epitope achieved excellent diagnostic accuracy. We map 79 B cell epitopes throughout the SARS-CoV-2 proteome and demonstrate that antibodies that develop in response to SARS-CoV-2 infection bind homologous peptide sequences in the six other known human CoVs. We also confirm reactivity against four of our top-ranking epitopes by enzyme-linked immunosorbent assay (ELISA). Illness severity correlated with increased reactivity to nine SARS-CoV-2 epitopes in S, M, N, and ORF3a in our population. Our results demonstrate previously unknown, highly reactive B cell epitopes throughout the full proteome of SARS-CoV-2 and other CoV proteins.
Keywords	covid19
Language	English
Publishing date	2021-01-08
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.10.10.334292
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Article: Fever, Diarrhea, and Severe Disease Correlate with High Persistent Antibody Levels against SARS-CoV-2.

Amjadi, Maya F / O'Connell, Sarah E / Armbrust, Tammy / Mergaert, Aisha M / Narpala, Sandeep R / Halfmann, Peter J / Bashar, S Janna / Glover, Christopher R / Heffron, Anna S / Taylor, Alison / Flach, Britta / O'Connor, David H / Kawaoka, Yoshihiro / McDermott, Adrian B / Sethi, Ajay K / Shelef, Miriam A

medRxiv : the preprint server for health sciences

2021

Abstract: Lasting immunity will be critical for overcoming the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, factors that drive the development of high titers of anti-SARS-CoV-2 ... ...

Abstract	Lasting immunity will be critical for overcoming the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, factors that drive the development of high titers of anti-SARS-CoV-2 antibodies and how long those antibodies persist remain unclear. Our objective was to comprehensively evaluate anti-SARS-CoV-2 antibodies in a clinically diverse COVID-19 convalescent cohort at defined time points to determine if anti-SARS-CoV-2 antibodies persist and to identify clinical and demographic factors that correlate with high titers. Using a novel multiplex assay to quantify IgG against four SARS-CoV-2 antigens, a receptor binding domain-angiotensin converting enzyme 2 inhibition assay, and a SARS-CoV-2 neutralization assay, we found that 98% of COVID-19 convalescent subjects had anti-SARS-CoV-2 antibodies five weeks after symptom resolution (n=113). Further, antibody levels did not decline three months after symptom resolution (n=79). As expected, greater disease severity, older age, male sex, obesity, and higher Charlson Comorbidity Index score correlated with increased anti-SARS-CoV-2 antibody levels. We demonstrated for the first time that COVID-19 symptoms, namely fever, abdominal pain, diarrhea and low appetite, correlated consistently with higher anti-SARS-CoV-2 antibody levels. Our results provide new insights into the development and persistence of anti-SARS-CoV-2 antibodies.
Language	English
Publishing date	2021-01-06
Publishing country	United States
Document type	Preprint
DOI	10.1101/2021.01.05.21249240
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Article ; Online: The landscape of antibody binding in SARS-CoV-2 infection.

Heffron, Anna S / McIlwain, Sean J / Amjadi, Maya F / Baker, David A / Khullar, Saniya / Armbrust, Tammy / Halfmann, Peter J / Kawaoka, Yoshihiro / Sethi, Ajay K / Palmenberg, Ann C / Shelef, Miriam A / O'Connor, David H / Ong, Irene M

PLoS biology

2021 Volume 19, Issue 6, Page(s) e3001265

Abstract	The search for potential antibody-based diagnostics, vaccines, and therapeutics for pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has focused almost exclusively on the spike (S) and nucleocapsid (N) proteins. Coronavirus membrane (M), ORF3a, and ORF8 proteins are humoral immunogens in other coronaviruses (CoVs) but remain largely uninvestigated for SARS-CoV-2. Here, we use ultradense peptide microarray mapping to show that SARS-CoV-2 infection induces robust antibody responses to epitopes throughout the SARS-CoV-2 proteome, particularly in M, in which 1 epitope achieved excellent diagnostic accuracy. We map 79 B cell epitopes throughout the SARS-CoV-2 proteome and demonstrate that antibodies that develop in response to SARS-CoV-2 infection bind homologous peptide sequences in the 6 other known human CoVs. We also confirm reactivity against 4 of our top-ranking epitopes by enzyme-linked immunosorbent assay (ELISA). Illness severity correlated with increased reactivity to 9 SARS-CoV-2 epitopes in S, M, N, and ORF3a in our population. Our results demonstrate previously unknown, highly reactive B cell epitopes throughout the full proteome of SARS-CoV-2 and other CoV proteins.
MeSH term(s)	Antibodies, Viral/blood ; Antibodies, Viral/immunology ; COVID-19/immunology ; COVID-19/pathology ; Coronavirus/immunology ; Cross Reactions ; Epitopes, B-Lymphocyte ; Humans ; Immunodominant Epitopes ; Immunoglobulin G/blood ; Immunoglobulin G/immunology ; Proteome/immunology ; SARS-CoV-2/immunology ; Severity of Illness Index ; Viral Proteins/immunology
Chemical Substances	Antibodies, Viral ; Epitopes, B-Lymphocyte ; Immunodominant Epitopes ; Immunoglobulin G ; Proteome ; Viral Proteins
Language	English
Publishing date	2021-06-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2126776-5
ISSN	1545-7885 ; 1544-9173
ISSN (online)	1545-7885
ISSN	1544-9173
DOI	10.1371/journal.pbio.3001265
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Zs.A 6193: Show issues

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Article ; Online: Specific COVID-19 Symptoms Correlate with High Antibody Levels against SARS-CoV-2.

ImmunoHorizons

2021 Volume 5, Issue 6, Page(s) 466–476

Abstract: Lasting immunity will be critical for overcoming COVID-19. However, the factors associated with the development of high titers of anti-SARS-CoV-2 Abs and how long those Abs persist remain incompletely defined. In particular, an understanding of the ... ...

Abstract	Lasting immunity will be critical for overcoming COVID-19. However, the factors associated with the development of high titers of anti-SARS-CoV-2 Abs and how long those Abs persist remain incompletely defined. In particular, an understanding of the relationship between COVID-19 symptoms and anti-SARS-CoV-2 Abs is limited. To address these unknowns, we quantified serum anti-SARS- CoV-2 Abs in clinically diverse COVID-19 convalescent human subjects 5 wk (
MeSH term(s)	Adult ; Antibodies, Neutralizing/blood ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/blood ; Antibodies, Viral/immunology ; COVID-19/epidemiology ; COVID-19/immunology ; COVID-19/virology ; Cohort Studies ; Female ; Hospitalization/statistics & numerical data ; Humans ; Immunoglobulin G/blood ; Immunoglobulin G/immunology ; Linear Models ; Male ; Middle Aged ; Multivariate Analysis ; Pandemics ; SARS-CoV-2/immunology ; SARS-CoV-2/physiology ; Severity of Illness Index ; Time Factors
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Immunoglobulin G
Language	English
Publishing date	2021-06-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2573-7732
ISSN (online)	2573-7732
DOI	10.4049/immunohorizons.2100022
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Article ; Online: The landscape of antibody binding in SARS-CoV-2 infection.

Anna S Heffron / Sean J McIlwain / Maya F Amjadi / David A Baker / Saniya Khullar / Tammy Armbrust / Peter J Halfmann / Yoshihiro Kawaoka / Ajay K Sethi / Ann C Palmenberg / Miriam A Shelef / David H O'Connor / Irene M Ong

PLoS Biology, Vol 19, Iss 6, p e

2021 Volume 3001265

Abstract	The search for potential antibody-based diagnostics, vaccines, and therapeutics for pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has focused almost exclusively on the spike (S) and nucleocapsid (N) proteins. Coronavirus membrane (M), ORF3a, and ORF8 proteins are humoral immunogens in other coronaviruses (CoVs) but remain largely uninvestigated for SARS-CoV-2. Here, we use ultradense peptide microarray mapping to show that SARS-CoV-2 infection induces robust antibody responses to epitopes throughout the SARS-CoV-2 proteome, particularly in M, in which 1 epitope achieved excellent diagnostic accuracy. We map 79 B cell epitopes throughout the SARS-CoV-2 proteome and demonstrate that antibodies that develop in response to SARS-CoV-2 infection bind homologous peptide sequences in the 6 other known human CoVs. We also confirm reactivity against 4 of our top-ranking epitopes by enzyme-linked immunosorbent assay (ELISA). Illness severity correlated with increased reactivity to 9 SARS-CoV-2 epitopes in S, M, N, and ORF3a in our population. Our results demonstrate previously unknown, highly reactive B cell epitopes throughout the full proteome of SARS-CoV-2 and other CoV proteins.
Keywords	Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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