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Article: Jean-Louis Berlandier, ein fast vergessener Naturforscher von Mexiko und Texas mit einem entscheidenden Beitrag zur Rettung des europäischen Weinbaus vor der Reblaus

Rühl, Ernst

2023 Volume 74, Issue -, Page(s) 11

Language	German
Document type	Article
ZDB-ID	525550-8
ISSN	0343-3714
Database	Current Contents Nutrition, Environment, Agriculture

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Article: Jean-Louis Berlandier, ein fast vergessener Naturforscher von Mexiko und Texas mit einem entscheidenden Beitrag zur Rettung des europäischen Weinbaus vor der Reblaus

Rühl, Ernst

Deutsches Weinbau-Jahrbuch

2023 Volume 74, Issue -, Page(s) 11

Language	German
Document type	Article
ZDB-ID	525550-8
ISSN	0343-3714
Database	Current Contents Nutrition, Environment, Agriculture

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Article ; Online: Third SARS-CoV-2 vaccination and breakthrough infections enhance humoral and cellular immunity against variants of concern.

Ruhl, Louisa / Kühne, Jenny F / Beushausen, Kerstin / Keil, Jana / Christoph, Stella / Sauer, Jasper / Falk, Christine S

Frontiers in immunology

2023 Volume 14, Page(s) 1120010

Abstract: Introduction: SARS-CoV-2 vaccination is the leading strategy to prevent severe courses after SARS-CoV-2 infection. In our study, we analyzed humoral and cellular immune responses in detail to three consecutive homologous or heterologous SARS-CoV-2 ... ...

Abstract	Introduction: SARS-CoV-2 vaccination is the leading strategy to prevent severe courses after SARS-CoV-2 infection. In our study, we analyzed humoral and cellular immune responses in detail to three consecutive homologous or heterologous SARS-CoV-2 vaccinations and breakthrough infections. Methods: Peripheral blood samples of n=20 individuals were analyzed in the time course of three SARS-CoV-2 vaccinations and/or breakthrough infection. S1-, RBD-, S2- and N-specific IgG antibodies were quantified using Luminex-based multiplex assays and electrochemiluminescence multiplex assays for surrogate neutralization in plasma. Changes in cellular immune components were determined via flow cytometry of whole blood samples. Results: All individuals (n=20) responded to vaccination with increasing S1-/RBD-/S2-specific IgG levels, whereas specific plasma IgA displayed individual variability. The third dose increased antibody inhibitory capacity (AIC) against immune-escape variants Beta and Omicron BA.1 independently of age. The mRNA-primed vaccination induced IgG and IgA immunity more efficiently, whereas vector-primed individuals displayed higher levels of memory T and B cells. Vaccinees showed SARS-CoV-2-specific T cell responses, which were further improved and specified after Omicron breakthrough infections in parallel to the appearance of new variant-specific antibodies. Discussion: In conclusion, the third vaccination was essential to increase IgG levels, mandatory to boost AIC against immune-escape variants, and induced SARS-CoV-2-specific T cells. Breakthrough infection with Omicron generates additional spike specificities covering all known variants.
MeSH term(s)	Humans ; COVID-19 Vaccines ; SARS-CoV-2 ; Breakthrough Infections ; COVID-19/prevention & control ; Immunity, Cellular ; Immunoglobulin G ; Vaccination ; Immunoglobulin A
Chemical Substances	COVID-19 Vaccines ; Immunoglobulin G ; Immunoglobulin A
Language	English
Publishing date	2023-03-22
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1120010
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Blood T cell phenotypes correlate with fatigue severity in post-acute sequelae of COVID-19.

Pink, Isabell / Hennigs, Jan K / Ruhl, Louisa / Sauer, Andrea / Boblitz, Lennart / Huwe, Marie / Fuge, Jan / Falk, Christine S / Pietschmann, Thomas / de Zwaan, Martina / Prasse, Antje / Kluge, Stefan / Klose, Hans / Hoeper, Marius M / Welte, Tobias

Infection

2023 Volume 52, Issue 2, Page(s) 513–524

Abstract: Purpose: Post-acute sequelae of COVID-19 (PASC) affect approximately 10% of convalescent patients. The spectrum of symptoms is broad and heterogeneous with fatigue being the most often reported sequela. Easily accessible blood biomarkers to determine ... ...

Abstract	Purpose: Post-acute sequelae of COVID-19 (PASC) affect approximately 10% of convalescent patients. The spectrum of symptoms is broad and heterogeneous with fatigue being the most often reported sequela. Easily accessible blood biomarkers to determine PASC severity are lacking. Thus, our study aimed to correlate immune phenotypes with PASC across the severity spectrum of COVID-19. Methods: A total of 176 originally immunonaïve, convalescent COVID-19 patients from a prospective cohort during the first pandemic phase were stratified by initial disease severity and underwent clinical, psychosocial, and immune phenotyping around 10 weeks after first COVID-19 symptoms. COVID-19-associated fatigue dynamics were assessed and related to clinical and immune phenotypes. Results: Fatigue and severe fatigue were commonly reported irrespective of initial COVID-19 severity or organ-specific PASC. A clinically relevant increase in fatigue severity after COVID-19 was detected in all groups. Neutralizing antibody titers were higher in patients with severe acute disease, but no association was found between antibody titers and PASC. While absolute peripheral blood immune cell counts in originally immunonaïve PASC patients did not differ from unexposed controls, peripheral CD3 Conclusions: Patients were at similar risk of self-reported PASC irrespective of initial disease severity. The independent correlation between fatigue severity and blood T cell phenotypes indicates a possible role of CD4
MeSH term(s)	Humans ; T-Lymphocytes ; Post-Acute COVID-19 Syndrome ; COVID-19/complications ; Prospective Studies ; Phenotype ; Disease Progression ; Fatigue/etiology
Language	English
Publishing date	2023-11-04
Publishing country	Germany
Document type	Journal Article
ZDB-ID	185104-4
ISSN	1439-0973 ; 0300-8126 ; 0173-2129
ISSN (online)	1439-0973
ISSN	0300-8126 ; 0173-2129
DOI	10.1007/s15010-023-02114-8
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Article ; Online: Triple COVID-19 vaccination induces humoral and cellular immunity to SARS-CoV-2 with cross-recognition of the Omicron variant and IgA secretion

Ruhl, Louisa / Kuehne, Jenny F / Beushausen, Kerstin / Keil, Jana / Christoph, Stella / Sauer, Jasper / Falk, Christine S

bioRxiv

Abstract: COVID-19 vaccination is the leading strategy to prevent severe courses after SARS-CoV-2 infection. In our study, we analyzed humoral and cellular immune responses in detail to three consecutive homologous or heterologous COVID-19 vaccinations. All ... ...

Abstract	COVID-19 vaccination is the leading strategy to prevent severe courses after SARS-CoV-2 infection. In our study, we analyzed humoral and cellular immune responses in detail to three consecutive homologous or heterologous COVID-19 vaccinations. All individuals (n=20) responded to vaccination with increasing S1-/RBD-/S2-specific IgG levels, whereas specific plasma IgA displayed individual variability. The third dose increased antibody inhibitory capacity (AIC) against immune-escape variants Beta and Omicron independently from age. The mRNA-primed vaccination induced IgG and IgA immunity more efficiently, whereas vector-primed individuals displayed higher levels of memory T and B cells. Vaccinees showed a SARS-CoV-2-specific T cell responses, which were further improved and specified after Omicron breakthrough infections in parallel to appearance of new variant-specific antibodies. In conclusion, the third vaccination was essential to increase IgG levels, mandatory to boost AIC against immune-escape variants and induced SARS-CoV-2-specific T cells. Breakthrough infection with Omicron generates additional spike specificities covering all known variants.
Keywords	covid19
Language	English
Publishing date	2022-09-22
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2022.09.22.508999
Database	COVID19

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Article ; Online: Triple COVID-19 vaccination induces humoral and cellular immunity to SARS-CoV-2 with cross-recognition of the Omicron variant and IgA secretion

Ruhl, Louisa / Kühne, Jenny F. / Beushausen, Kerstin / Keil, Jana / Christoph, Stella / Sauer, Jasper / Falk, Christine S.

bioRxiv

Abstract	COVID-19 vaccination is the leading strategy to prevent severe courses after SARS-CoV-2 infection. In our study, we analyzed humoral and cellular immune responses in detail to three consecutive homologous or heterologous COVID-19 vaccinations. All individuals (n=20) responded to vaccination with increasing S1-/RBD-/S2-specific IgG levels, whereas specific plasma IgA displayed individual variability. The third dose increased antibody inhibitory capacity (AIC) against immune-escape variants Beta and Omicron independently from age. The mRNA-primed vaccination induced IgG and IgA immunity more efficiently, whereas vector-primed individuals displayed higher levels of memory T and B cells. Vaccinees showed a SARS-CoV-2-specific T cell responses, which were further improved and specified after Omicron breakthrough infections in parallel to appearance of new variant-specific antibodies. In conclusion, the third vaccination was essential to increase IgG levels, mandatory to boost AIC against immune-escape variants and induced SARS-CoV-2-specific T cells. Breakthrough infection with Omicron generates additional spike specificities covering all known variants.
Keywords	covid19
Language	English
Publishing date	2022-09-22
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2022.09.22.508999
Database	COVID19

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Article ; Online: CAR-Ts redirected against the Thomsen-Friedenreich antigen CD176 mediate specific elimination of malignant cells from leukemia and solid tumors.

Frontiers in immunology

2023 Volume 14, Page(s) 1219165

Abstract: Introduction: Chimeric antigen receptor-engineered T cells (CAR-Ts) are investigated in various clinical trials for the treatment of cancer entities beyond hematologic malignancies. A major hurdle is the identification of a target antigen with high ... ...

Abstract	Introduction: Chimeric antigen receptor-engineered T cells (CAR-Ts) are investigated in various clinical trials for the treatment of cancer entities beyond hematologic malignancies. A major hurdle is the identification of a target antigen with high expression on the tumor but no expression on healthy cells, since "on-target/off-tumor" cytotoxicity is usually intolerable. Approximately 90% of carcinomas and leukemias are positive for the Thomsen-Friedenreich carbohydrate antigen CD176, which is associated with tumor progression, metastasis and therapy resistance. In contrast, CD176 is not accessible for ligand binding on healthy cells due to prolongation by carbohydrate chains or sialylation. Thus, no "on-target/off-tumor" cytotoxicity and low probability of antigen escape is expected for corresponding CD176-CAR-Ts. Methods: Using the anti-CD176 monoclonal antibody (mAb) Nemod-TF2, the presence of CD176 was evaluated on multiple healthy or cancerous tissues and cells. To target CD176, we generated two different 2 Results: Specific expression of CD176 was detected on primary tumor tissues as well as on cell lines from corresponding blood and solid cancer entities. CD176-CARs mediated T-cell signaling (NF-κB activation) and T-cell activation (CD69, CD137 expression) upon recognition of CD176 Discussion: Genetically engineered CD176-CAR-Ts specifically recognize CD176 which is widely expressed on cancer cells. Since CD176 is masked on most healthy cells, this antigen and the corresponding CAR-Ts represent a promising approach for the treatment of various blood and solid cancers while avoiding "on-target/off-tumor" cytotoxicity.
MeSH term(s)	Humans ; CD8-Positive T-Lymphocytes ; Antigens, Tumor-Associated, Carbohydrate ; Leukemia ; Carbohydrates
Chemical Substances	Thomsen-Friedenreich antigen (3554-90-3) ; Antigens, Tumor-Associated, Carbohydrate ; Carbohydrates
Language	English
Publishing date	2023-10-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1219165
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Article ; Online: Reduced humoral but stable cellular SARS-CoV-2-specific immunity in liver transplant recipients in the first year after COVID-19.

Kirchner, Theresa / Heinrich, Sophia / Bonifacius, Agnes / Engel, Bastian / Ruhl, Louisa / Pink, Isabell / Thomas, Nele / Martens, Joerg / Hoeper, Marius M / Blasczyk, Rainer / Wedemeyer, Heiner / Jaeckel, Elmar / Li, Yang / Falk, Christine S / Eiz-Vesper, Britta / Taubert, Richard

PloS one

2022 Volume 17, Issue 11, Page(s) e0276929

Abstract: Mortality due to COVID-19 is not increased in immunosuppressed individuals after liver transplantation (OLT) compared to individuals without immunosuppression. Data on long-term protective immunity against SARS-CoV-2 in immunosuppressed convalescents, is ...

Abstract	Mortality due to COVID-19 is not increased in immunosuppressed individuals after liver transplantation (OLT) compared to individuals without immunosuppression. Data on long-term protective immunity against SARS-CoV-2 in immunosuppressed convalescents, is limited. We prospectively measured immune responses against SARS-CoV-2 by quantifying antibodies against 4 different antigens (spike protein 1 and 2, receptor binding domain, nucleocapsid) and T cell responses by IFN-γ ELISPOT against 4 antigens (membrane, nucleocapsid, spike protein 1 and 2) in 24 OLT convalescents with immunosuppressive therapy longitudinally in the first year after COVID-19 including a booster vaccination in comparison to a matched cohort of non-immunosuppressed convalescents (non-IS-Con). Pre-pandemic OLT samples were retrieved from our prospective OLT biorepository (n = 16). No relevant T cell reactivity or immunoglobulin G (IgG) against SARS-CoV-2 were detectable in pre-pandemic samples of OLT recipients despite reactivity against endemic corona-viruses. OLT convalescents had a lower prevalence of IgG against nucleocapsid (54% vs. 90%) but not against spike protein domains (98-100% vs. 100%) after vaccination in the second half-year after COVID-19 compared to non-IS-Con. Also, concentrations of anti-nucleocapsid IgG were lower in OLT convalescents than in non-IS-Con. Concentration of IgG against spike protein domains was significantly increased by a booster vaccination in OLT convalescents. But concentration of IgG against two of three spike protein domains remains slightly lower compared to non-IS-Con finally. However, none of these differences was mirrored by the cellular immunity against SARS-CoV-2 that remained stable during the first year after COVID-19 and was not further stimulated by a corona vaccination in OLT convalescents. In conclusion, despite lower concentrations of anti-SARS-CoV-2 IgG in OLT convalescents anti-SARS-CoV-2 cellular immunity was as robust as in non-IS-Con.
MeSH term(s)	Humans ; SARS-CoV-2 ; COVID-19 ; Spike Glycoprotein, Coronavirus ; Liver Transplantation ; Prospective Studies ; Antibodies, Viral ; Immunoglobulin G ; Immunity, Cellular ; Immunity, Humoral ; Vaccination ; Transplant Recipients
Chemical Substances	Spike Glycoprotein, Coronavirus ; Antibodies, Viral ; Immunoglobulin G ; spike protein, SARS-CoV-2
Language	English
Publishing date	2022-11-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0276929
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Reduced humoral but stable cellular SARS-CoV-2-specific immunity in liver transplant recipients in the first year after COVID-19.

Theresa Kirchner / Sophia Heinrich / Agnes Bonifacius / Bastian Engel / Louisa Ruhl / Isabell Pink / Nele Thomas / Joerg Martens / Marius M Hoeper / Rainer Blasczyk / Heiner Wedemeyer / Elmar Jaeckel / Yang Li / Christine S Falk / Britta Eiz-Vesper / Richard Taubert

PLoS ONE, Vol 17, Iss 11, p e

2022 Volume 0276929

Abstract	Mortality due to COVID-19 is not increased in immunosuppressed individuals after liver transplantation (OLT) compared to individuals without immunosuppression. Data on long-term protective immunity against SARS-CoV-2 in immunosuppressed convalescents, is limited. We prospectively measured immune responses against SARS-CoV-2 by quantifying antibodies against 4 different antigens (spike protein 1 and 2, receptor binding domain, nucleocapsid) and T cell responses by IFN-γ ELISPOT against 4 antigens (membrane, nucleocapsid, spike protein 1 and 2) in 24 OLT convalescents with immunosuppressive therapy longitudinally in the first year after COVID-19 including a booster vaccination in comparison to a matched cohort of non-immunosuppressed convalescents (non-IS-Con). Pre-pandemic OLT samples were retrieved from our prospective OLT biorepository (n = 16). No relevant T cell reactivity or immunoglobulin G (IgG) against SARS-CoV-2 were detectable in pre-pandemic samples of OLT recipients despite reactivity against endemic corona-viruses. OLT convalescents had a lower prevalence of IgG against nucleocapsid (54% vs. 90%) but not against spike protein domains (98-100% vs. 100%) after vaccination in the second half-year after COVID-19 compared to non-IS-Con. Also, concentrations of anti-nucleocapsid IgG were lower in OLT convalescents than in non-IS-Con. Concentration of IgG against spike protein domains was significantly increased by a booster vaccination in OLT convalescents. But concentration of IgG against two of three spike protein domains remains slightly lower compared to non-IS-Con finally. However, none of these differences was mirrored by the cellular immunity against SARS-CoV-2 that remained stable during the first year after COVID-19 and was not further stimulated by a corona vaccination in OLT convalescents. In conclusion, despite lower concentrations of anti-SARS-CoV-2 IgG in OLT convalescents anti-SARS-CoV-2 cellular immunity was as robust as in non-IS-Con.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Endothelial dysfunction contributes to severe COVID-19 in combination with dysregulated lymphocyte responses and cytokine networks.

Ruhl, Louisa / Pink, Isabell / Kühne, Jenny F / Beushausen, Kerstin / Keil, Jana / Christoph, Stella / Sauer, Andrea / Boblitz, Lennart / Schmidt, Julius / David, Sascha / Jäck, Hans-Martin / Roth, Edith / Cornberg, Markus / Schulz, Thomas F / Welte, Tobias / Höper, Marius M / Falk, Christine S

Signal transduction and targeted therapy

2021 Volume 6, Issue 1, Page(s) 418

Abstract: The systemic processes involved in the manifestation of life-threatening COVID-19 and in disease recovery are still incompletely understood, despite investigations focusing on the dysregulation of immune responses after SARS-CoV-2 infection. To define ... ...

Abstract	The systemic processes involved in the manifestation of life-threatening COVID-19 and in disease recovery are still incompletely understood, despite investigations focusing on the dysregulation of immune responses after SARS-CoV-2 infection. To define hallmarks of severe COVID-19 in acute disease (n = 58) and in disease recovery in convalescent patients (n = 28) from Hannover Medical School, we used flow cytometry and proteomics data with unsupervised clustering analyses. In our observational study, we combined analyses of immune cells and cytokine/chemokine networks with endothelial activation and injury. ICU patients displayed an altered immune signature with prolonged lymphopenia but the expansion of granulocytes and plasmablasts along with activated and terminally differentiated T and NK cells and high levels of SARS-CoV-2-specific antibodies. The core signature of seven plasma proteins revealed a highly inflammatory microenvironment in addition to endothelial injury in severe COVID-19. Changes within this signature were associated with either disease progression or recovery. In summary, our data suggest that besides a strong inflammatory response, severe COVID-19 is driven by endothelial activation and barrier disruption, whereby recovery depends on the regeneration of the endothelial integrity.
MeSH term(s)	Antibodies, Viral/blood ; Biomarkers/blood ; Blood Proteins/metabolism ; C-Reactive Protein/metabolism ; COVID-19/diagnosis ; COVID-19/immunology ; COVID-19/mortality ; COVID-19/virology ; Chemokine CXCL10/blood ; Chemokine CXCL9/blood ; Cluster Analysis ; Convalescence ; Cytokine Release Syndrome/diagnosis ; Cytokine Release Syndrome/immunology ; Cytokine Release Syndrome/mortality ; Cytokine Release Syndrome/virology ; Disease Progression ; Endothelium, Vascular/immunology ; Endothelium, Vascular/virology ; Granulocytes/immunology ; Granulocytes/virology ; Hematopoietic Cell Growth Factors/blood ; Hepatocyte Growth Factor/blood ; Humans ; Intensive Care Units ; Interleukin-12 Subunit p40/blood ; Interleukin-6/blood ; Interleukin-8/blood ; Killer Cells, Natural/immunology ; Killer Cells, Natural/virology ; Lectins, C-Type/blood ; Lymphopenia/diagnosis ; Lymphopenia/immunology ; Lymphopenia/mortality ; Lymphopenia/virology ; Plasma Cells/immunology ; Plasma Cells/virology ; SARS-CoV-2/pathogenicity ; Survival Analysis ; T-Lymphocytes/immunology ; T-Lymphocytes/virology
Chemical Substances	Antibodies, Viral ; Biomarkers ; Blood Proteins ; CLEC11A protein, human ; CXCL10 protein, human ; CXCL8 protein, human ; CXCL9 protein, human ; Chemokine CXCL10 ; Chemokine CXCL9 ; HGF protein, human ; Hematopoietic Cell Growth Factors ; IL6 protein, human ; Interleukin-12 Subunit p40 ; Interleukin-6 ; Interleukin-8 ; Lectins, C-Type ; Hepatocyte Growth Factor (67256-21-7) ; C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2021-12-10
Publishing country	England
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2886872-9
ISSN	2059-3635 ; 2095-9907
ISSN (online)	2059-3635
ISSN	2095-9907
DOI	10.1038/s41392-021-00819-6
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