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Article ; Online: Lung dendritic cells migrate to the spleen to prime long-lived TCF1

Jenkins, Meagan M / Bachus, Holly / Botta, Davide / Schultz, Michael D / Rosenberg, Alexander F / León, Beatriz / Ballesteros-Tato, André

Science immunology

2021 Volume 6, Issue 63, Page(s) eabg6895

Abstract: ... ...

Abstract	CD8
MeSH term(s)	Animals ; CD8-Positive T-Lymphocytes/immunology ; Cell Movement/immunology ; Dendritic Cells/immunology ; Hepatocyte Nuclear Factor 1-alpha/immunology ; Humans ; Lung/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Orthomyxoviridae Infections/immunology ; Precursor Cells, T-Lymphoid/immunology ; Spleen/immunology
Chemical Substances	Hepatocyte Nuclear Factor 1-alpha ; Hnf1a protein, mouse
Language	English
Publishing date	2021-09-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.abg6895
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A single intranasal administration of AdCOVID protects against SARS-CoV-2 infection in the upper and lower respiratory tracts.

Schultz, Michael D / Suschak, John J / Botta, Davide / Silva-Sanchez, Aaron / King, R Glenn / Detchemendy, Thomas W / Meshram, Chetan D / Foote, Jeremy B / Zhou, Fen / Tipper, Jennifer L / Zhang, Jianfeng / Harrod, Kevin S / Leal, Sixto M / Randall, Troy D / Roberts, M Scot / Georges, Bertrand / Lund, Frances E

Human vaccines & immunotherapeutics

2022 Volume 18, Issue 6, Page(s) 2127292

Abstract: The coronavirus disease 2019 (COVID-19) pandemic has illustrated the critical need for effective prophylactic vaccination to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Intranasal vaccination is an attractive ... ...

Abstract	The coronavirus disease 2019 (COVID-19) pandemic has illustrated the critical need for effective prophylactic vaccination to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Intranasal vaccination is an attractive approach for preventing COVID-19 as the nasal mucosa is the site of initial SARS-CoV-2 entry and viral replication prior to aspiration into the lungs. We previously demonstrated that a single intranasal administration of a candidate adenovirus type 5-vectored vaccine encoding the receptor-binding domain of the SARS-CoV-2 spike protein (AdCOVID) induced robust immunity in both the airway mucosa and periphery, and completely protected K18-hACE2 mice from lethal SARS-CoV-2 challenge. Here we show that a single intranasal administration of AdCOVID limits viral replication in the nasal cavity of K18-hACE2 mice. AdCOVID also induces sterilizing immunity in the lungs of mice as reflected by the absence of infectious virus. Finally, AdCOVID prevents SARS-CoV-2 induced pathological damage in the lungs of mice. These data show that AdCOVID not only limits viral replication in the respiratory tract, but it also prevents virus-induced inflammation and immunopathology following SARS-CoV-2 infection.
MeSH term(s)	Animals ; Humans ; Mice ; Administration, Intranasal ; Antibodies, Viral ; COVID-19/prevention & control ; Lung ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus ; Viral Vaccines/administration & dosage ; COVID-19 Vaccines/administration & dosage
Chemical Substances	Antibodies, Viral ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Viral Vaccines ; COVID-19 Vaccines
Language	English
Publishing date	2022-10-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	2664176-8
ISSN	2164-554X ; 2164-5515
ISSN (online)	2164-554X
ISSN	2164-5515
DOI	10.1080/21645515.2022.2127292
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Zs.A 6967: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: The establishment of resident memory B cells in the lung requires local antigen encounter.

Allie, S Rameeza / Bradley, John E / Mudunuru, Uma / Schultz, Michael D / Graf, Beth A / Lund, Frances E / Randall, Troy D

Nature immunology

2018 Volume 20, Issue 1, Page(s) 97–108

Abstract: Memory B cells are found in lymphoid and non-lymphoid tissues, suggesting that some may be tissue-resident cells. Here we show that pulmonary influenza infection elicited lung-resident memory B cells (BRM cells) that were phenotypically and functionally ... ...

Abstract	Memory B cells are found in lymphoid and non-lymphoid tissues, suggesting that some may be tissue-resident cells. Here we show that pulmonary influenza infection elicited lung-resident memory B cells (BRM cells) that were phenotypically and functionally distinct from their systemic counterparts. BRM cells were established in the lung early after infection, in part because their placement required local antigen encounter. Lung BRM cells, but not systemic memory B cells, contributed to early plasmablast responses following challenge infection. Following secondary infection, antigen-specific BRM cells differentiated in situ, whereas antigen-non-specific BRM cells were maintained as memory cells. These data demonstrate that BRM cells are an important component of immunity to respiratory viruses such as influenza virus and suggest that vaccines designed to elicit BRM cells must deliver antigen to the lungs.
MeSH term(s)	Animals ; Antigens, Viral/immunology ; B-Lymphocytes/immunology ; Cell Differentiation ; Cells, Cultured ; Female ; Humans ; Immunity, Humoral ; Immunologic Memory ; Influenza Vaccines/immunology ; Influenza, Human/immunology ; Lung/immunology ; Lung/virology ; Lymphocyte Activation ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Orthomyxoviridae/physiology ; Orthomyxoviridae Infections/immunology ; Plasma Cells/immunology
Chemical Substances	Antigens, Viral ; Influenza Vaccines
Language	English
Publishing date	2018-12-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-018-0260-6
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Zs.A 5294: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 42: Show issues

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Article ; Online: Inhibition of the NAD salvage pathway in schistosomes impairs metabolism, reproduction, and parasite survival.

Schultz, Michael D / Dadali, Tulin / Jacques, Sylvain A / Muller-Steffner, Hélène / Foote, Jeremy B / Sorci, Leonardo / Kellenberger, Esther / Botta, Davide / Lund, Frances E

PLoS pathogens

2020 Volume 16, Issue 5, Page(s) e1008539

Abstract: NAD, a key co-enzyme required for cell metabolism, is synthesized via two pathways in most organisms. Since schistosomes apparently lack enzymes required for de novo NAD biosynthesis, we evaluated whether these parasites, which infect >200 million people ...

Abstract	NAD, a key co-enzyme required for cell metabolism, is synthesized via two pathways in most organisms. Since schistosomes apparently lack enzymes required for de novo NAD biosynthesis, we evaluated whether these parasites, which infect >200 million people worldwide, maintain NAD homeostasis via the NAD salvage biosynthetic pathway. We found that intracellular NAD levels decline in schistosomes treated with drugs that block production of nicotinamide or nicotinamide mononucleotide-known NAD precursors in the non-deamidating salvage pathway. Moreover, in vitro inhibition of the NAD salvage pathway in schistosomes impaired egg production, disrupted the outer membranes of both immature and mature parasites and caused loss of mobility and death. Inhibiting the NAD salvage pathway in schistosome-infected mice significantly decreased NAD levels in adult parasites, which correlated with reduced egg production, fewer liver granulomas and parasite death. Thus, schistosomes, unlike their mammalian hosts, appear limited to one metabolic pathway to maintain NAD-dependent metabolic processes.
MeSH term(s)	Animals ; Female ; Host-Parasite Interactions/physiology ; Mice ; NAD/metabolism ; Reproduction/physiology ; Schistosoma mansoni/physiology ; Schistosomiasis mansoni/metabolism ; Schistosomiasis mansoni/pathology
Chemical Substances	NAD (0U46U6E8UK)
Language	English
Publishing date	2020-05-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1008539
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Book ; Online: Atmospheric circulation patterns, cloud-to-ground lightning, and locally intense convective rainfall associated with debris flow initiation in the Dolomite Alps of northeastern Italy

Underwood, S. Jeffrey / Schultz, Michael D. / Berti, Metteo / Gregoretti, Carlo / Simoni, Alessandro / Mote, Thomas L. / Saylor, Anthony M.

eISSN: 1684-9981

2018

Abstract: The Dolomite Alps of northeastern Italy experience debris flows with great frequency during the summer months. An ample supply of unconsolidated material on steep slopes and a summer season climate regime characterized by recurrent thunderstorms combine ... ...

Abstract	The Dolomite Alps of northeastern Italy experience debris flows with great frequency during the summer months. An ample supply of unconsolidated material on steep slopes and a summer season climate regime characterized by recurrent thunderstorms combine to produce an abundance of these destructive hydro-geologic events. In the past, debris flow events have been studied primarily in the context of their geologic and geomorphic characteristics. The atmospheric contribution to these mass-wasting events has been limited to recording rainfall and developing intensity thresholds for debris mobilization. This study aims to expand the examination of atmospheric processes that preceded both locally intense convective rainfall (LICR) and debris flows in the Dolomite region. 500 hPa pressure level plots of geopotential heights were constructed for a period of 3 days prior to debris flow events to gain insight into the synoptic-scale processes which provide an environment conducive to LICR in the Dolomites. Cloud-to-ground (CG) lightning flash data recorded at the meso-scale were incorporated to assess the convective environment proximal to debris flow source regions. Twelve events were analyzed and from this analysis three common synoptic-scale circulation patterns were identified. Evaluation of CG flashes at smaller spatial and temporal scales illustrated that convective processes vary in their production of CF flashes (total number) and the spatial distribution of flashes can also be quite different between events over longer periods. During the 60 min interval immediately preceding debris flow a majority of cases exhibited spatial and temporal colocation of LICR and CG flashes. Also a number of CG flash parameters were found to be significantly correlated to rainfall intensity prior to debris flow initiation.
Subject code	910
Language	English
Publishing date	2018-09-27
Publishing country	de
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Efficient Inhibition of SmNACE by Coordination Complexes Is Abolished by S. mansoni Sequestration of Metal.

Muller-Steffner, Hélène / Jacques, Sylvain A / Kuhn, Isabelle / Schultz, Michael D / Botta, Davide / Osswald, Paul / Maechling, Clarisse / Lund, Frances E / Kellenberger, Esther

ACS chemical biology

2017 Volume 12, Issue 7, Page(s) 1787–1795

Abstract: SmNACE is a NAD catabolizing enzyme expressed on the outer tegument of S. mansoni, a human parasite that is one of the major agents of the neglected tropical disease schistosomiasis. Recently, we identified aroylhydrazone derivatives capable of ... ...

Abstract	SmNACE is a NAD catabolizing enzyme expressed on the outer tegument of S. mansoni, a human parasite that is one of the major agents of the neglected tropical disease schistosomiasis. Recently, we identified aroylhydrazone derivatives capable of inhibiting the recombinant form of the enzyme with variable potency (IC
MeSH term(s)	Animals ; Coordination Complexes/pharmacology ; Enzyme Activation/drug effects ; Enzyme Activation/physiology ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/pharmacology ; Inhibitory Concentration 50 ; Metals/metabolism ; Molecular Structure ; Schistosoma mansoni/enzymology ; Schistosoma mansoni/metabolism ; Zinc/chemistry
Chemical Substances	Coordination Complexes ; Enzyme Inhibitors ; Metals ; Zinc (J41CSQ7QDS)
Language	English
Publishing date	2017--21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1554-8937
ISSN (online)	1554-8937
DOI	10.1021/acschembio.7b00186
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: T-bet Transcription Factor Promotes Antibody-Secreting Cell Differentiation by Limiting the Inflammatory Effects of IFN-γ on B Cells.

Immunity

2019 Volume 50, Issue 5, Page(s) 1172–1187.e7

Abstract: Although viral infections elicit robust interferon-γ (IFN-γ) and long-lived antibody-secreting cell (ASC) responses, the roles for IFN-γ and IFN-γ-induced transcription factors (TFs) in ASC development are unclear. We showed that B cell intrinsic ... ...

Abstract	Although viral infections elicit robust interferon-γ (IFN-γ) and long-lived antibody-secreting cell (ASC) responses, the roles for IFN-γ and IFN-γ-induced transcription factors (TFs) in ASC development are unclear. We showed that B cell intrinsic expression of IFN-γR and the IFN-γ-induced TF T-bet were required for T-helper 1 cell-induced differentiation of B cells into ASCs. IFN-γR signaling induced Blimp1 expression in B cells but also initiated an inflammatory gene program that, if not restrained, prevented ASC formation. T-bet did not affect Blimp1 upregulation in IFN-γ-activated B cells but instead regulated chromatin accessibility within the Ifng and Ifngr2 loci and repressed the IFN-γ-induced inflammatory gene program. Consistent with this, B cell intrinsic T-bet was required for formation of long-lived ASCs and secondary ASCs following viral, but not nematode, infection. Therefore, T-bet facilitates differentiation of IFN-γ-activated inflammatory effector B cells into ASCs in the setting of IFN-γ-, but not IL-4-, induced inflammatory responses.
MeSH term(s)	Animals ; Antibody-Producing Cells/immunology ; B-Lymphocytes/cytology ; B-Lymphocytes/immunology ; Cell Differentiation/immunology ; Cells, Cultured ; Chromatin/metabolism ; Influenza A Virus, H1N1 Subtype/immunology ; Influenza A Virus, H3N2 Subtype/immunology ; Interferon-gamma/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nematospiroides dubius/immunology ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/virology ; Positive Regulatory Domain I-Binding Factor 1/biosynthesis ; Receptors, Interferon/metabolism ; Strongylida Infections/immunology ; Strongylida Infections/parasitology ; T-Box Domain Proteins/genetics ; T-Box Domain Proteins/metabolism ; T-Lymphocytes, Helper-Inducer/immunology ; Interferon gamma Receptor
Chemical Substances	Chromatin ; Prdm1 protein, mouse ; Receptors, Interferon ; T-Box Domain Proteins ; T-box transcription factor TBX21 ; Interferon-gamma (82115-62-6) ; Positive Regulatory Domain I-Binding Factor 1 (EC 2.1.1.-)
Language	English
Publishing date	2019-05-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2019.04.004
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Zs.A 4227: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 69: Show issues

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Article: Single-dose intranasal administration of AdCOVID elicits systemic and mucosal immunity against SARS-CoV-2 in mice.

King, Rodney G / Silva-Sanchez, Aaron / Peel, Jessica N / Botta, Davide / Meza-Perez, Selene / Allie, Rameeza / Schultz, Michael D / Liu, Mingyong / Bradley, John E / Qiu, Shihong / Yang, Guang / Zhou, Fen / Zumaquero, Esther / Simpler, Thomas S / Mousseau, Betty / Killian, John T / Dean, Brittany / Shang, Qiao / Tipper, Jennifer L /

Risley, Christopher / Harrod, Kevin S / Feng, Ray / Lee, Young / Shiberu, Bethlehem / Krishnan, Vyjayanthi / Peguillet, Isabelle / Zhang, Jianfeng / Green, Todd / Randall, Troy D / Georges, Bertrand / Lund, Frances E / Roberts, Scot

bioRxiv : the preprint server for biology

2020

Abstract: The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective preventive vaccination to reduce burden and spread of severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) in humans. Intranasal vaccination is ... ...

Abstract	The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective preventive vaccination to reduce burden and spread of severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) in humans. Intranasal vaccination is an attractive strategy to prevent COVID-19 as the nasal mucosa represents the first-line barrier to SARS-CoV-2 entry before viral spread to the lung. Although SARS-CoV-2 vaccine development is rapidly progressing, the current intramuscular vaccines are designed to elicit systemic immunity without conferring mucosal immunity. Here, we show that AdCOVID, an intranasal adenovirus type 5 (Ad5)-vectored vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, elicits a strong and focused immune response against RBD through the induction of mucosal IgA, serum neutralizing antibodies and CD4+ and CD8+ T cells with a Th1-like cytokine expression profile. Therefore, AdCOVID, which promotes concomitant systemic and local mucosal immunity, represents a promising COVID-19 vaccine candidate.
Keywords	covid19
Language	English
Publishing date	2020-10-11
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.10.10.331348
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Article: Single-Dose Intranasal Administration of AdCOVID Elicits Systemic and Mucosal Immunity against SARS-CoV-2 and Fully Protects Mice from Lethal Challenge.

King, R Glenn / Silva-Sanchez, Aaron / Peel, Jessica N / Botta, Davide / Dickson, Alexandria M / Pinto, Amelia K / Meza-Perez, Selene / Allie, S Rameeza / Schultz, Michael D / Liu, Mingyong / Bradley, John E / Qiu, Shihong / Yang, Guang / Zhou, Fen / Zumaquero, Esther / Simpler, Thomas S / Mousseau, Betty / Killian, John T / Dean, Brittany /

Shang, Qiao / Tipper, Jennifer L / Risley, Christopher A / Harrod, Kevin S / Feng, Tsungwei / Lee, Young / Shiberu, Bethlehem / Krishnan, Vyjayanthi / Peguillet, Isabelle / Zhang, Jianfeng / Green, Todd J / Randall, Troy D / Suschak, John J / Georges, Bertrand / Brien, James D / Lund, Frances E / Roberts, M Scot

Vaccines

2021 Volume 9, Issue 8

Abstract: The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective prophylactic vaccination to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Intranasal vaccination is an attractive ... ...

Abstract	The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective prophylactic vaccination to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Intranasal vaccination is an attractive strategy to prevent COVID-19 as the nasal mucosa represents the first-line barrier to SARS-CoV-2 entry. The current intramuscular vaccines elicit systemic immunity but not necessarily high-level mucosal immunity. Here, we tested a single intranasal dose of our candidate adenovirus type 5-vectored vaccine encoding the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (AdCOVID) in inbred, outbred, and transgenic mice. A single intranasal vaccination with AdCOVID elicited a strong and focused immune response against RBD through the induction of mucosal IgA in the respiratory tract, serum neutralizing antibodies, and CD4
Language	English
Publishing date	2021-08-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines9080881
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Article ; Online: Single-dose intranasal administration of AdCOVID elicits systemic and mucosal immunity against SARS-CoV-2 in mice

King, Rodney G. / Silva-Sanchez, Aaron / Peel, Jessica N. / Botta, Davide / Meza-Perez, Selene / Allie, Rameeza / Schultz, Michael D. / Liu, Mingyong / Bradley, John E. / Qiu, Shihong / Yang, Guang / Zhou, Fen / Zumaquero, Esther / Simpler, Thomas S. / Mousseau, Betty / Killian, John T. / Dean, Brittany / Shang, Qiao / Tipper, Jennifer L. /

Risley, Christopher / Harrod, Kevin S. / Feng, Ray / Lee, Young / Shiberu, Bethlehem / Krishnan, Vyjayanthi / Peguillet, Isabelle / Zhang, Jianfeng / Green, Todd / Randall, Troy D. / Georges, Bertrand / Lund, Frances E / Roberts, Scot

bioRxiv

Abstract	The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective preventive vaccination to reduce burden and spread of severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) in humans. Intranasal vaccination is an attractive strategy to prevent COVID-19 as the nasal mucosa represents the first-line barrier to SARS-CoV-2 entry before viral spread to the lung. Although SARS-CoV-2 vaccine development is rapidly progressing, the current intramuscular vaccines are designed to elicit systemic immunity without conferring mucosal immunity. Here, we show that AdCOVID, an intranasal adenovirus type 5 (Ad5)-vectored vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, elicits a strong and focused immune response against RBD through the induction of mucosal IgA, serum neutralizing antibodies and CD4+ and CD8+ T cells with a Th1-like cytokine expression profile. Therefore, AdCOVID, which promotes concomitant systemic and local mucosal immunity, represents a promising COVID-19 vaccine candidate.
Keywords	covid19
Language	English
Publishing date	2020-10-11
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2020.10.10.331348
Database	COVID19

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