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Article ; Online: Revisiting the Role of Neurotrophic Factors in Inflammation.

Morel, Lucas / Domingues, Olivia / Zimmer, Jacques / Michel, Tatiana

2020 Volume 9, Issue 4

Abstract: The neurotrophic factors are well known for their implication in the growth and the survival of the central, sensory, enteric and parasympathetic nervous systems. Due to these properties, neurturin (NRTN) and Glial cell-derived neurotrophic factor (GDNF), ...

Abstract	The neurotrophic factors are well known for their implication in the growth and the survival of the central, sensory, enteric and parasympathetic nervous systems. Due to these properties, neurturin (NRTN) and Glial cell-derived neurotrophic factor (GDNF), which belong to the GDNF family ligands (GFLs), have been assessed in clinical trials as a treatment for neurodegenerative diseases like Parkinson's disease. In addition, studies in favor of a functional role for GFLs outside the nervous system are accumulating. Thus, GFLs are present in several peripheral tissues, including digestive, respiratory, hematopoietic and urogenital systems, heart, blood, muscles and skin. More precisely, recent data have highlighted that different types of immune and epithelial cells (macrophages, T cells, such as, for example, mucosal-associated invariant T (MAIT) cells, innate lymphoid cells (ILC) 3, dendritic cells, mast cells, monocytes, bronchial epithelial cells, keratinocytes) have the capacity to release GFLs and express their receptors, leading to the participation in the repair of epithelial barrier damage after inflammation. Some of these mechanisms pass on to ILCs to produce cytokines (such as IL-22) that can impact gut microbiota. In addition, there are indications that NRTN could be used in the treatment of inflammatory airway diseases and it prevents the development of hyperglycemia in the diabetic rat model. On the other hand, it is suspected that the dysregulation of GFLs produces oncogenic effects. This review proposes the discussion of the biological understanding and the potential new opportunities of the GFLs, in the perspective of developing new treatments within a broad range of human diseases.
MeSH term(s)	Animals ; Disease Models, Animal ; Glial Cell Line-Derived Neurotrophic Factor/genetics ; Humans ; Inflammation/physiopathology ; Mice ; Nerve Growth Factors/genetics
Chemical Substances	Glial Cell Line-Derived Neurotrophic Factor ; Nerve Growth Factors
Language	English
Publishing date	2020-04-02
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells9040865
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Article ; Online: Nanoluciferase-based cell fusion assay for rapid and high-throughput assessment of SARS-CoV-2-neutralizing antibodies in patient samples.

Meyrath, Max / Szpakowska, Martyna / Plesseria, Jean-Marc / Domingues, Olivia / Langlet, Jérémie / Weber, Bernard / Krüger, Rejko / Ollert, Markus / Chevigné, Andy

Methods in enzymology

2022 Volume 675, Page(s) 351–381

Abstract: After more than two years, COVID-19 still represents a global health burden of unprecedented extent and assessing the degree of immunity of individuals against SARS-CoV-2 remains a challenge. Virus neutralization assays represent the gold standard for ... ...

Abstract	After more than two years, COVID-19 still represents a global health burden of unprecedented extent and assessing the degree of immunity of individuals against SARS-CoV-2 remains a challenge. Virus neutralization assays represent the gold standard for assessing antibody-mediated protection against SARS-CoV-2 in sera from recovered and/or vaccinated individuals. Neutralizing antibodies block the interaction of viral spike protein with human angiotensin-converting enzyme 2 (ACE2) receptor in vitro and prevent viral entry into host cells. Classical viral neutralization assays using full replication-competent viruses are restricted to specific biosafety level 3-certified laboratories, limiting their utility for routine and large-scale applications. We developed therefore a cell-fusion-based assay building on the interaction between viral spike and ACE2 receptor expressed on two different cell lines, substantially reducing biosafety risks associated with classical viral neutralization assays. This chapter describes this simple, sensitive, safe and cost-effective approach for rapid and high-throughput evaluation of SARS-CoV-2 neutralizing antibodies relying on high-affinity NanoLuc® luciferase complementation technology (HiBiT). When applied to a variety of standards and patient samples, this method yields highly reproducible results in 96-well, as well as in 384-well format. The use of novel NanoLuc® substrates with increased signal stability like Nano-Glo® Endurazine™ furthermore allows for high flexibility in assay set-up and full automatization of all reading processes. Lastly, the assay is suitable to evaluate the neutralizing capacity of sera against the existing spike variants, and potentially variants that will emerge in the future.
MeSH term(s)	Angiotensin-Converting Enzyme 2 ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Cell Fusion ; Humans ; Luciferases ; Neutralization Tests/methods ; Peptidyl-Dipeptidase A/metabolism ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/metabolism
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Luciferases (EC 1.13.12.-) ; nanoluc (EC 1.13.12.-) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2022-09-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1557-7988
ISSN (online)	1557-7988
DOI	10.1016/bs.mie.2022.07.015
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Article ; Online: Allergic airway inflammation delays glioblastoma progression and reinvigorates systemic and local immunity in mice

Poli, Aurélie / Oudin, Anaïs / Muller, Arnaud / Salvato, Ilaria / Scafidi, Andrea / Hunewald, Oliver / Domingues, Olivia / Nazarov, Petr V. / Puard, Vincent / Baus, Virginie / Azuaje, Francisco / Dittmar, Gunnar / Zimmer, Jacques / Michel, Tatiana / Michelucci, Alessandro / Niclou, Simone P. / Ollert, Markus

Allergy. 2023 Mar., v. 78, no. 3, p. 682-696

2023 , Page(s) 682–696

Abstract: BACKGROUND: Numerous patient‐based studies have highlighted the protective role of immunoglobulin E‐mediated allergic diseases on glioblastoma (GBM) susceptibility and prognosis. However, the mechanisms behind this observation remain elusive. Our ... ...

Abstract	BACKGROUND: Numerous patient‐based studies have highlighted the protective role of immunoglobulin E‐mediated allergic diseases on glioblastoma (GBM) susceptibility and prognosis. However, the mechanisms behind this observation remain elusive. Our objective was to establish a preclinical model able to recapitulate this phenomenon and investigate the role of immunity underlying such protection. METHODS: An immunocompetent mouse model of allergic airway inflammation (AAI) was initiated before intracranial implantation of mouse GBM cells (GL261). RAG1‐KO mice served to assess tumor growth in a model deficient for adaptive immunity. Tumor development was monitored by MRI. Microglia were isolated for functional analyses and RNA‐sequencing. Peripheral as well as tumor‐associated immune cells were characterized by flow cytometry. The impact of allergy‐related microglial genes on patient survival was analyzed by Cox regression using publicly available datasets. RESULTS: We found that allergy establishment in mice delayed tumor engraftment in the brain and reduced tumor growth resulting in increased mouse survival. AAI induced a transcriptional reprogramming of microglia towards a pro‐inflammatory‐like state, uncovering a microglia gene signature, which correlated with limited local immunosuppression in glioma patients. AAI increased effector memory T‐cells in the circulation as well as tumor‐infiltrating CD4⁺T‐cells. The survival benefit conferred by AAI was lost in mice devoid of adaptive immunity. CONCLUSION: Our results demonstrate that AAI limits both tumor take and progression in mice, providing a preclinical model to study the impact of allergy on GBM susceptibility and prognosis, respectively. We identify a potentiation of local and adaptive systemic immunity, suggesting a reciprocal crosstalk that orchestrates allergy‐induced immune protection against GBM.
Keywords	T-lymphocytes ; adaptive immunity ; brain ; data collection ; flow cytometry ; genes ; glioblastoma ; hypersensitivity ; immunoglobulins ; immunosuppression ; inflammation ; mice ; models ; neuroglia ; patients ; prognosis ; protective effect ; regression analysis ; sequence analysis ; transcription (genetics)
Language	English
Dates of publication	2023-03
Size	p. 682-696
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	391933-x
ISSN	1398-9995 ; 0105-4538
ISSN (online)	1398-9995
ISSN	0105-4538
DOI	10.1111/all.15545
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Imprint of Initial Education and Loss of Ly49C/I in Activated Natural Killer Cells of TAP1-KO and C57BL/6 Wildtype Mice.

Patil, Neha D / Domingues, Olivia / Masquelier, Cécile / Theresine, Maud / Schlienger, Oceane / Njinju Amin Asaba, Clinton / Thomas, Marine / Seguin-Devaux, Carole / Slevogt, Hortense / Ollert, Markus / Zimmer, Jacques

Frontiers in immunology

2022 Volume 13, Page(s) 818015

Abstract: Natural killer (NK) cells are important effectors of the innate immune system and participate in the first line of defense against infections and tumors. Prior to being functional, these lymphocytes must be educated or licensed through interactions of ... ...

Abstract	Natural killer (NK) cells are important effectors of the innate immune system and participate in the first line of defense against infections and tumors. Prior to being functional, these lymphocytes must be educated or licensed through interactions of their major histocompatibility complex class I molecules with self-specific inhibitory receptors that recognize them. In the absence of such contacts, caused by either the lack of expression of the inhibitory receptors or a very low level of major histocompatibility complex class I (MHC class I) proteins, NK cells are hypo-reactive at baseline (
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily B, Member 2/genetics ; Animals ; Antigen Presentation ; Histocompatibility Antigens Class I ; Killer Cells, Natural ; Membrane Transport Proteins/metabolism ; Mice ; Mice, Inbred C57BL ; NK Cell Lectin-Like Receptor Subfamily A/immunology ; NK Cell Lectin-Like Receptor Subfamily A/metabolism
Chemical Substances	ATP Binding Cassette Transporter, Subfamily B, Member 2 ; Histocompatibility Antigens Class I ; Klra3 protein, mouse ; Membrane Transport Proteins ; NK Cell Lectin-Like Receptor Subfamily A
Language	English
Publishing date	2022-07-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.818015
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Article ; Online: Pre-Omicron Vaccine Breakthrough Infection Induces Superior Cross-Neutralization against SARS-CoV-2 Omicron BA.1 Compared to Infection Alone.

da Silva, Eveline Santos / Kohnen, Michel / Gilson, Georges / Staub, Therese / Arendt, Victor / Hilger, Christiane / Servais, Jean-Yves / Charpentier, Emilie / Domingues, Olivia / Snoeck, Chantal J / Ollert, Markus / Seguin-Devaux, Carole / Perez-Bercoff, Danielle

International journal of molecular sciences

2022 Volume 23, Issue 14

Abstract: SARS-CoV-2 variants raise concern because of their high transmissibility and their ability to evade neutralizing antibodies elicited by prior infection or by vaccination. Here, we compared the neutralizing abilities of sera from 70 unvaccinated COVID-19 ... ...

Abstract	SARS-CoV-2 variants raise concern because of their high transmissibility and their ability to evade neutralizing antibodies elicited by prior infection or by vaccination. Here, we compared the neutralizing abilities of sera from 70 unvaccinated COVID-19 patients infected before the emergence of variants of concern (VOCs) and of 16 vaccine breakthrough infection (BTI) cases infected with Gamma or Delta against the ancestral B.1 strain, the Gamma, Delta and Omicron BA.1 VOCs using live virus. We further determined antibody levels against the Nucleocapsid (N) and full Spike proteins, the receptor-binding domain (RBD) and the N-terminal domain (NTD) of the Spike protein. Convalescent sera featured considerable variability in the neutralization of B.1 and in the cross-neutralization of different strains. Their neutralizing capacity moderately correlated with antibody levels against the Spike protein and the RBD. All but one convalescent serum failed to neutralize Omicron BA.1. Overall, convalescent sera from patients with moderate disease had higher antibody levels and displayed a higher neutralizing ability against all strains than patients with mild or severe forms of the disease. The sera from BTI cases fell into one of two categories: half the sera had a high neutralizing activity against the ancestral B.1 strain as well as against the infecting strain, while the other half had no or a very low neutralizing activity against all strains. Although antibody levels against the spike protein and the RBD were lower in BTI sera than in unvaccinated convalescent sera, most neutralizing sera also retained partial neutralizing activity against Omicron BA.1, suggestive of a better cross-neutralization and higher affinity of vaccine-elicited antibodies over virus-induced antibodies. Accordingly, the IC50: antibody level ratios were comparable for BTI and convalescent sera, but remained lower in the neutralizing convalescent sera from patients with moderate disease than in BTI sera. The neutralizing activity of BTI sera was strongly correlated with antibodies against the Spike protein and the RBD. Together, these findings highlight qualitative differences in antibody responses elicited by infection in vaccinated and unvaccinated individuals. They further indicate that breakthrough infection with a pre-Omicron variant boosts immunity and induces cross-neutralizing antibodies against different strains, including Omicron BA.1.
MeSH term(s)	Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19/prevention & control ; COVID-19/therapy ; Humans ; Immunization, Passive ; Neutralization Tests ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Vaccines ; COVID-19 Serotherapy
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus ; Vaccines ; spike protein, SARS-CoV-2
Language	English
Publishing date	2022-07-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23147675
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Article ; Online: Allergic airway inflammation delays glioblastoma progression and reinvigorates systemic and local immunity in mice.

Poli, Aurélie / Oudin, Anaïs / Muller, Arnaud / Salvato, Ilaria / Scafidi, Andrea / Hunewald, Oliver / Domingues, Olivia / Nazarov, Petr V / Puard, Vincent / Baus, Virginie / Azuaje, Francisco / Dittmar, Gunnar / Zimmer, Jacques / Michel, Tatiana / Michelucci, Alessandro / Niclou, Simone P / Ollert, Markus

Allergy

2022 Volume 78, Issue 3, Page(s) 682–696

Abstract: Background: Numerous patient-based studies have highlighted the protective role of immunoglobulin E-mediated allergic diseases on glioblastoma (GBM) susceptibility and prognosis. However, the mechanisms behind this observation remain elusive. Our ... ...

Abstract	Background: Numerous patient-based studies have highlighted the protective role of immunoglobulin E-mediated allergic diseases on glioblastoma (GBM) susceptibility and prognosis. However, the mechanisms behind this observation remain elusive. Our objective was to establish a preclinical model able to recapitulate this phenomenon and investigate the role of immunity underlying such protection. Methods: An immunocompetent mouse model of allergic airway inflammation (AAI) was initiated before intracranial implantation of mouse GBM cells (GL261). RAG1-KO mice served to assess tumor growth in a model deficient for adaptive immunity. Tumor development was monitored by MRI. Microglia were isolated for functional analyses and RNA-sequencing. Peripheral as well as tumor-associated immune cells were characterized by flow cytometry. The impact of allergy-related microglial genes on patient survival was analyzed by Cox regression using publicly available datasets. Results: We found that allergy establishment in mice delayed tumor engraftment in the brain and reduced tumor growth resulting in increased mouse survival. AAI induced a transcriptional reprogramming of microglia towards a pro-inflammatory-like state, uncovering a microglia gene signature, which correlated with limited local immunosuppression in glioma patients. AAI increased effector memory T-cells in the circulation as well as tumor-infiltrating CD4 Conclusion: Our results demonstrate that AAI limits both tumor take and progression in mice, providing a preclinical model to study the impact of allergy on GBM susceptibility and prognosis, respectively. We identify a potentiation of local and adaptive systemic immunity, suggesting a reciprocal crosstalk that orchestrates allergy-induced immune protection against GBM.
MeSH term(s)	Mice ; Animals ; Glioblastoma/genetics ; Glioblastoma/pathology ; Brain Neoplasms/pathology ; Glioma/genetics ; Glioma/pathology ; Microglia/pathology ; Hypersensitivity/pathology ; Mice, Inbred C57BL
Language	English
Publishing date	2022-10-18
Publishing country	Denmark
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	391933-x
ISSN	1398-9995 ; 0105-4538
ISSN (online)	1398-9995
ISSN	0105-4538
DOI	10.1111/all.15545
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Article ; Online: Early-to-mid stage idiopathic Parkinson's disease shows enhanced cytotoxicity and differentiation in CD8 T-cells in females.

Capelle, Christophe M / Ciré, Séverine / Hedin, Fanny / Hansen, Maxime / Pavelka, Lukas / Grzyb, Kamil / Kyriakis, Dimitrios / Hunewald, Oliver / Konstantinou, Maria / Revets, Dominique / Tslaf, Vera / Marques, Tainá M / Gomes, Clarissa P C / Baron, Alexandre / Domingues, Olivia / Gomez, Mario / Zeng, Ni / Betsou, Fay / May, Patrick /

Skupin, Alexander / Cosma, Antonio / Balling, Rudi / Krüger, Rejko / Ollert, Markus / Hefeng, Feng Q

Nature communications

2023 Volume 14, Issue 1, Page(s) 7461

Abstract: Neuroinflammation in the brain contributes to the pathogenesis of Parkinson's disease (PD), but the potential dysregulation of peripheral immunity has not been systematically investigated for idiopathic PD (iPD). Here we showed an elevated peripheral ... ...

Abstract	Neuroinflammation in the brain contributes to the pathogenesis of Parkinson's disease (PD), but the potential dysregulation of peripheral immunity has not been systematically investigated for idiopathic PD (iPD). Here we showed an elevated peripheral cytotoxic immune milieu, with more terminally-differentiated effector memory (TEMRA) CD8 T, CD8
MeSH term(s)	Humans ; Female ; Parkinson Disease/genetics ; CD8-Positive T-Lymphocytes ; Cell Differentiation ; Immunologic Memory
Language	English
Publishing date	2023-11-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-43053-0
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Article ; Online: Comprehensive mapping of immune tolerance yields a regulatory TNF receptor 2 signature in a murine model of successful Fel d 1-specific immunotherapy using high-dose CpG adjuvant.

Leonard, Cathy / Montamat, Guillem / Davril, Caroline / Domingues, Olivia / Hunewald, Oliver / Revets, Dominique / Guerin, Coralie / Blank, Simon / Heckendorn, Justine / Jardon, Gauthier / Hentges, François / Ollert, Markus

Allergy

2021 Volume 76, Issue 7, Page(s) 2153–2165

Abstract: Background: The prevalence of allergy to cat is expanding worldwide. Allergen-specific immunotherapy (AIT) has advantages over symptomatic pharmacotherapy and promises long-lasting disease control in allergic patients. However, there is still a need to ... ...

Abstract	Background: The prevalence of allergy to cat is expanding worldwide. Allergen-specific immunotherapy (AIT) has advantages over symptomatic pharmacotherapy and promises long-lasting disease control in allergic patients. However, there is still a need to improve cat AIT regarding efficacy, safety, and adherence to the treatment. Here, we aim to boost immune tolerance to the major cat allergen Fel d 1 by increasing the anti-inflammatory activity of AIT with the established immunomodulatory adjuvant CpG, but at a higher dose than previously used in AIT. Methods: Together with CpG, we used endotoxin-free Fel d 1 as therapeutic allergen throughout the study in a BALB/c model of allergy to Fel d 1, thus mimicking the conditions of human AIT trials. Multidimensional immune phenotyping including mass cytometry (CyTOF) was applied to analyze AIT-specific immune signatures. Results: We show that AIT with high-dose CpG in combination with endotoxin-free Fel d 1 reverts all major hallmarks of allergy. High-dimensional CyTOF analysis of the immune cell signatures initiating and sustaining the AIT effect indicates the simultaneous engagement of both, the pDC-Treg and B-cell axis, with the emergence of a systemic GATA3 Conclusion: Our results highlight the potential of CpG adjuvant in a novel formulation to be further exploited for inducing allergen-specific tolerance in patients with cat allergy or other allergic diseases.
MeSH term(s)	Allergens ; Animals ; Cats ; Desensitization, Immunologic ; Disease Models, Animal ; Glycoproteins/immunology ; Humans ; Hypersensitivity/therapy ; Immune Tolerance ; Mice ; Receptors, Tumor Necrosis Factor, Type II
Chemical Substances	Allergens ; Glycoproteins ; Receptors, Tumor Necrosis Factor, Type II ; Fel d 1 protein, Felis domesticus (G408EE88II)
Language	English
Publishing date	2021-01-05
Publishing country	Denmark
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	391933-x
ISSN	1398-9995 ; 0105-4538
ISSN (online)	1398-9995
ISSN	0105-4538
DOI	10.1111/all.14716
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Article ; Online: Pre-Omicron vaccine breakthrough infection induces superior cross-neutralization against SARS-CoV-2 Omicron BA.1 than primo infection

Santos da Silva, Eveline / Kohnen, Michel / Gilson, Georges / Staub, Therese / Arendt, Victor / Servais, Jean-Yves / Charpentier, Emilie / Domingues, Olivia / Snoeck, Chantal J / Ollert, Markus / Seguin-Devaux, Carole / Perez-Bercoff, Danielle

medRxiv

Abstract: SARS-CoV-2 variants raise concern because of their high transmissibility and their ability to evade neutralizing antibodies elicited by prior infection or by vaccination. Here we compared the ability of sera from 70 unvaccinated COVID-19 patients ... ...

Abstract	SARS-CoV-2 variants raise concern because of their high transmissibility and their ability to evade neutralizing antibodies elicited by prior infection or by vaccination. Here we compared the ability of sera from 70 unvaccinated COVID-19 patients infected before the emergence of variants of concern (VOCs) and from 16 vaccine breakthrough infection (BTI) cases infected with Gamma or Delta to neutralize the ancestral B.1 strain, and the Gamma, Delta and Omicron BA.1 variants using live virus. We further determined antibody levels against the Spike protein, the Receptor Binding Domain (RBD) and the N-terminal domain (NTD) of Spike. Convalescent sera featured considerable variability in neutralization of B.1 and in cross-neutralization of different strains, and neutralizing capacity moderately correlated with antibody levels against Spike and the RBD. All but one convalescent serum failed to neutralize Omicron BA.1. Overall, convalescent sera from patients with moderate disease had higher antibody levels and displayed higher neutralizing ability against all strains than patients with mild or severe forms of disease. Sera from BTI cases fell into one of two categories: half the sera had high neutralizing activity against the ancestral B.1 strain as well as against the infecting strain, while the other half had no or very low neutralizing activity against all strains. Although antibody levels against Spike and the RBD were lower in BTI cases than in unvaccinated convalescent sera, most neutralizing sera also retained partial neutralizing activity against Omicron BA.1, indicative of cross-neutralization between B.1, Delta and Omicron and suggestive of higher affinity, as confirmed by the IC50:Ab level ratios. Neutralizing activity of BTI sera was strongly correlated with antibodies against Spike and the RBD. Together, these findings highlight qualitative differences in antibody responses elicited by infection in vaccinated and unvaccinated individuals. They further suggest that breakthrough infection with a pre-Omicron variant boosts immunity and induces cross neutralizing antibodies against different strains, including Omicron BA.1.
Keywords	covid19
Language	English
Publishing date	2022-06-23
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2022.06.21.22276659
Database	COVID19

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Article ; Online: Combinatorial analysis reveals highly coordinated early-stage immune reactions that predict later antiviral immunity in mild COVID-19 patients.

Capelle, Christophe M / Ciré, Séverine / Domingues, Olivia / Ernens, Isabelle / Hedin, Fanny / Fischer, Aurélie / Snoeck, Chantal J / Ammerlaan, Wim / Konstantinou, Maria / Grzyb, Kamil / Skupin, Alexander / Carty, Cara L / Hilger, Christiane / Gilson, Georges / Celebic, Aljosa / Wilmes, Paul / Del Sol, Antonio / Kaplan, Ian M / Betsou, Fay /

Abdelrahman, Tamir / Cosma, Antonio / Vaillant, Michel / Fagherazzi, Guy / Ollert, Markus / Hefeng, Feng Q

Cell reports. Medicine

2022 Volume 3, Issue 4, Page(s) 100600

Abstract: While immunopathology has been widely studied in patients with severe COVID-19, immune responses in non-hospitalized patients have remained largely elusive. We systematically analyze 484 peripheral cellular or soluble immune features in a longitudinal ... ...

Abstract	While immunopathology has been widely studied in patients with severe COVID-19, immune responses in non-hospitalized patients have remained largely elusive. We systematically analyze 484 peripheral cellular or soluble immune features in a longitudinal cohort of 63 mild and 15 hospitalized patients versus 14 asymptomatic and 26 household controls. We observe a transient increase of IP10/CXCL10 and interferon-β levels, coordinated responses of dominant SARS-CoV-2-specific CD4 and fewer CD8 T cells, and various antigen-presenting and antibody-secreting cells in mild patients within 3 days of PCR diagnosis. The frequency of key innate immune cells and their functional marker expression are impaired in hospitalized patients at day 1 of inclusion. T cell and dendritic cell responses at day 1 are highly predictive for SARS-CoV-2-specific antibody responses after 3 weeks in mild but not hospitalized patients. Our systematic analysis reveals a combinatorial picture and trajectory of various arms of the highly coordinated early-stage immune responses in mild COVID-19 patients.
MeSH term(s)	Antibodies, Viral ; Antiviral Agents ; CD8-Positive T-Lymphocytes ; COVID-19 ; Humans ; SARS-CoV-2
Chemical Substances	Antibodies, Viral ; Antiviral Agents
Language	English
Publishing date	2022-03-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2666-3791
ISSN (online)	2666-3791
DOI	10.1016/j.xcrm.2022.100600
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