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Article ; Online: A TLR4 agonist liposome formulation effectively stimulates innate immunity and enhances protection from bacterial infection.

Hedges, Jodi F / Snyder, Deann T / Robison, Amanda / Thompson, Macy A / Aspelin, Klara / Plewa, Jack / Baldridge, Jory / Jutila, Mark A

Innate immunity

2023 Volume 29, Issue 3-4, Page(s) 45–57

Abstract: Stimulation of innate immunity can protect against infectious insult and could be used in combination with other therapies. Since antibiotic resistance is an increasing concern, strategies to reduce the dose or eliminate the need for these drugs are ... ...

Abstract	Stimulation of innate immunity can protect against infectious insult and could be used in combination with other therapies. Since antibiotic resistance is an increasing concern, strategies to reduce the dose or eliminate the need for these drugs are warranted. Lipo-CRX is a formulation in which the TLR4 agonist CRX-527 is incorporated into lipid membranes in liposomes. Lipo-CRX is less inflammatory than either CRX-527 or LPS, but retains unique capacity to enhance host defense responses. We compared lipo-CRX to other agonists
MeSH term(s)	Animals ; Cattle ; Mice ; Brucella abortus ; Liposomes ; Toll-Like Receptor 4 ; Lipopolysaccharides/pharmacology ; Escherichia coli ; Immunity, Innate ; Brucellosis ; Mammals
Chemical Substances	AGP 527 ; Liposomes ; Toll-Like Receptor 4 ; Lipopolysaccharides ; Tlr4 protein, mouse
Language	English
Publishing date	2023-04-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	2381250-3
ISSN	1753-4267 ; 1753-4259
ISSN (online)	1753-4267
ISSN	1753-4259
DOI	10.1177/17534259231168725
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Titers, Prevalence, and Duration of SARS-CoV-2 Antibodies in a Local COVID-19 Outbreak and Following Vaccination.

Hedges, Jodi F / Thompson, Macy A / Snyder, Deann T / Robison, Amanda / Taylor, Matthew P / Jutila, Mark A

Vaccines

2021 Volume 9, Issue 6

Abstract: Information concerning the development of neutralizing antibodies and their duration will be critical to establishing herd immunity for COVID-19. We sought to evaluate SARS-CoV-2 spike protein receptor-binding domain (RBD)-specific antibodies, their ... ...

Abstract	Information concerning the development of neutralizing antibodies and their duration will be critical to establishing herd immunity for COVID-19. We sought to evaluate SARS-CoV-2 spike protein receptor-binding domain (RBD)-specific antibodies, their duration, and capacity for SARS-CoV-2 neutralization in volunteers while the pandemic spread within our community starting in March 2020. Those participants with the highest starting titers had the longest-lasting response, up to 12 months post-diagnosis. SARS-CoV-2 neutralization capacity was correlated with anti-RBD antibody levels. The majority of our participants with confirmed COVID-19 diagnosis had very mild or asymptomatic infections. We also detected low and largely non-neutralizing anti-RBD IgG titers in a few participants with no known COVID-19 diagnosis. Finally, we found that antibody responses induced by vaccination were significantly higher than those induced by natural infection. Thus, our study suggests that vaccination is still critical even for those naturally infected or diagnosed with COVID-19.
Language	English
Publishing date	2021-06-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines9060587
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Article ; Online: Getting "Inside" Type I IFNs: Type I IFNs in Intracellular Bacterial Infections.

Snyder, Deann T / Hedges, Jodi F / Jutila, Mark A

Journal of immunology research

2017 Volume 2017, Page(s) 9361802

Abstract: Type I interferons represent a unique and complex group of cytokines, serving many purposes during innate and adaptive immunity. Discovered in the context of viral infections, type I IFNs are now known to have myriad effects in infectious and autoimmune ... ...

Abstract	Type I interferons represent a unique and complex group of cytokines, serving many purposes during innate and adaptive immunity. Discovered in the context of viral infections, type I IFNs are now known to have myriad effects in infectious and autoimmune disease settings. Type I IFN signaling during bacterial infections is dependent on many factors including whether the infecting bacterium is intracellular or extracellular, as different signaling pathways are activated. As such, the repercussions of type I IFN induction can positively or negatively impact the disease outcome. This review focuses on type I IFN induction and downstream consequences during infection with the following intracellular bacteria:
MeSH term(s)	Animals ; Bacterial Infections/immunology ; Cytoplasm/immunology ; Cytoplasm/microbiology ; Humans ; Interferon Type I/immunology ; Listeria monocytogenes/immunology ; Listeria monocytogenes/physiology ; Listeriosis/immunology ; Macrophages/immunology ; Macrophages/microbiology ; Mice ; Salmonella typhimurium/immunology ; Salmonella typhimurium/physiology ; Signal Transduction
Chemical Substances	Interferon Type I
Language	English
Publishing date	2017-04-26
Publishing country	Egypt
Document type	Journal Article ; Review
ZDB-ID	2817541-4
ISSN	2314-7156 ; 2314-8861
ISSN (online)	2314-7156
ISSN	2314-8861
DOI	10.1155/2017/9361802
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Article ; Online: Titers, Prevalence, and Duration of SARS-CoV-2 Antibodies in a Local COVID-19 Outbreak and Following Vaccination

Jodi F. Hedges / Macy A. Thompson / Deann T. Snyder / Amanda Robison / Matthew P. Taylor / Mark A. Jutila

Vaccines, Vol 9, Iss 587, p

2021 Volume 587

Abstract	Information concerning the development of neutralizing antibodies and their duration will be critical to establishing herd immunity for COVID-19. We sought to evaluate SARS-CoV-2 spike protein receptor-binding domain (RBD)-specific antibodies, their duration, and capacity for SARS-CoV-2 neutralization in volunteers while the pandemic spread within our community starting in March 2020. Those participants with the highest starting titers had the longest-lasting response, up to 12 months post-diagnosis. SARS-CoV-2 neutralization capacity was correlated with anti-RBD antibody levels. The majority of our participants with confirmed COVID-19 diagnosis had very mild or asymptomatic infections. We also detected low and largely non-neutralizing anti-RBD IgG titers in a few participants with no known COVID-19 diagnosis. Finally, we found that antibody responses induced by vaccination were significantly higher than those induced by natural infection. Thus, our study suggests that vaccination is still critical even for those naturally infected or diagnosed with COVID-19.
Keywords	anti-RBD IgG ; antibodies ; SARS-CoV-2 ; COVID-19 ; neutralization ; duration ; Medicine ; R
Subject code	570
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: An ADAM17-Neutralizing Antibody Reduces Inflammation and Mortality While Increasing Viral Burden in a COVID-19 Mouse Model.

Hedges, Jodi F / Snyder, Deann T / Robison, Amanda / Grifka-Walk, Heather M / Blackwell, Karlin / Shepardson, Kelly / Kominsky, Douglas / Rynda-Apple, Agnieszka / Walcheck, Bruce / Jutila, Mark A

Frontiers in immunology

2022 Volume 13, Page(s) 918881

Abstract: Angiotensin Converting Enzyme 2 (ACE2) is the primary cell entry receptor for SARS-CoV and SARS-CoV-2 viruses. A disintegrin and metalloproteinase 17 (ADAM17) is a protease that cleaves ectodomains of transmembrane proteins, including that of ACE2 and ... ...

Abstract	Angiotensin Converting Enzyme 2 (ACE2) is the primary cell entry receptor for SARS-CoV and SARS-CoV-2 viruses. A disintegrin and metalloproteinase 17 (ADAM17) is a protease that cleaves ectodomains of transmembrane proteins, including that of ACE2 and the proinflammatory cytokine TNF-α, from cell surfaces upon cellular activation. We hypothesized that blockade of ADAM17 activity would alter COVID-19 pathogenesis. To assess this pathway, we blocked the function of ADAM17 using the monoclonal antibody MEDI3622 in the K18-hACE2 transgenic mouse model of COVID-19. Antibody-treated mice were healthier, less moribund, and had significantly lower lung pathology than saline-treated mice. However, the viral burden in the lungs of MEDI3622-treated mice was significantly increased. Thus, ADAM17 appears to have a critical anti-viral role, but also may promote inflammatory damage. Since the inflammatory cascade is ultimately the reason for adverse outcomes in COVID-19 patients, there may be a therapeutic application for the MEDI3622 antibody.
MeSH term(s)	ADAM17 Protein/antagonists & inhibitors ; ADAM17 Protein/immunology ; Angiotensin-Converting Enzyme 2/metabolism ; Animals ; Antibodies, Neutralizing/immunology ; Antibodies, Neutralizing/pharmacology ; COVID-19/immunology ; COVID-19/therapy ; COVID-19/virology ; Disease Models, Animal ; Humans ; Mice ; Mice, Transgenic ; Peptidyl-Dipeptidase A/metabolism ; SARS-CoV-2/immunology ; Viral Load
Chemical Substances	Antibodies, Neutralizing ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; ADAM17 Protein (EC 3.4.24.86) ; ADAM17 protein, human (EC 3.4.24.86)
Language	English
Publishing date	2022-06-10
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.2022.918881
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Article ; Online: Antiviral responses in a Jamaican fruit bat intestinal organoid model of SARS-CoV-2 infection.

Nature communications

2023 Volume 14, Issue 1, Page(s) 6882

Abstract: Bats are natural reservoirs for several zoonotic viruses, potentially due to an enhanced capacity to control viral infection. However, the mechanisms of antiviral responses in bats are poorly defined. Here we established a Jamaican fruit bat (JFB, ... ...

Abstract	Bats are natural reservoirs for several zoonotic viruses, potentially due to an enhanced capacity to control viral infection. However, the mechanisms of antiviral responses in bats are poorly defined. Here we established a Jamaican fruit bat (JFB, Artibeus jamaicensis) intestinal organoid model of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Upon infection with SARS-CoV-2, increased viral RNA and subgenomic RNA was detected, but no infectious virus was released, indicating that JFB organoids support only limited viral replication but not viral reproduction. SARS-CoV-2 replication was associated with significantly increased gene expression of type I interferons and inflammatory cytokines. Interestingly, SARS-CoV-2 also caused enhanced formation and growth of JFB organoids. Proteomics revealed an increase in inflammatory signaling, cell turnover, cell repair, and SARS-CoV-2 infection pathways. Collectively, our findings suggest that primary JFB intestinal epithelial cells mount successful antiviral interferon responses and that SARS-CoV-2 infection in JFB cells induces protective regenerative pathways.
MeSH term(s)	Animals ; COVID-19 ; Chiroptera ; SARS-CoV-2 ; Jamaica ; Viruses ; Interferon Type I ; Antiviral Agents ; Organoids
Chemical Substances	Interferon Type I ; Antiviral Agents
Language	English
Publishing date	2023-10-28
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-42610-x
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Article ; Online: Antiviral responses in a Jamaican fruit bat intestinal organoid model of SARS-CoV-2 infection

Nature Communications, Vol 14, Iss 1, Pp 1-

2023 Volume 15

Abstract: Abstract Bats are natural reservoirs for several zoonotic viruses, potentially due to an enhanced capacity to control viral infection. However, the mechanisms of antiviral responses in bats are poorly defined. Here we established a Jamaican fruit bat ( ... ...

Abstract	Abstract Bats are natural reservoirs for several zoonotic viruses, potentially due to an enhanced capacity to control viral infection. However, the mechanisms of antiviral responses in bats are poorly defined. Here we established a Jamaican fruit bat (JFB, Artibeus jamaicensis) intestinal organoid model of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Upon infection with SARS-CoV-2, increased viral RNA and subgenomic RNA was detected, but no infectious virus was released, indicating that JFB organoids support only limited viral replication but not viral reproduction. SARS-CoV-2 replication was associated with significantly increased gene expression of type I interferons and inflammatory cytokines. Interestingly, SARS-CoV-2 also caused enhanced formation and growth of JFB organoids. Proteomics revealed an increase in inflammatory signaling, cell turnover, cell repair, and SARS-CoV-2 infection pathways. Collectively, our findings suggest that primary JFB intestinal epithelial cells mount successful antiviral interferon responses and that SARS-CoV-2 infection in JFB cells induces protective regenerative pathways.
Keywords	Science ; Q
Subject code	570
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: SARS-CoV-2 genomic surveillance identifies naturally occurring truncation of ORF7a that limits immune suppression.

Nemudryi, Artem / Nemudraia, Anna / Wiegand, Tanner / Nichols, Joseph / Snyder, Deann T / Hedges, Jodi F / Cicha, Calvin / Lee, Helen / Vanderwood, Karl K / Bimczok, Diane / Jutila, Mark A / Wiedenheft, Blake

Cell reports

2021 Volume 35, Issue 9, Page(s) 109197

Abstract: Over 950,000 whole-genome sequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been determined for viruses isolated from around the world. These sequences are critical for understanding the spread and evolution of SARS-CoV-2. ... ...

Abstract	Over 950,000 whole-genome sequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been determined for viruses isolated from around the world. These sequences are critical for understanding the spread and evolution of SARS-CoV-2. Using global phylogenomics, we show that mutations frequently occur in the C-terminal end of ORF7a. We isolate one of these mutant viruses from a patient sample and use viral challenge experiments to link this isolate (ORF7a
MeSH term(s)	Animals ; COVID-19/immunology ; COVID-19/virology ; Chlorocebus aethiops ; Genome, Viral ; HEK293 Cells ; Humans ; Immunity ; Interferon Type I/immunology ; Mutation ; Phylogeny ; SARS-CoV-2/genetics ; SARS-CoV-2/pathogenicity ; Vero Cells ; Viral Proteins/genetics ; Viral Proteins/immunology ; Viral Regulatory and Accessory Proteins/genetics
Chemical Substances	Interferon Type I ; ORF7a protein, SARS-CoV-2 ; Viral Proteins ; Viral Regulatory and Accessory Proteins
Language	English
Publishing date	2021-05-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2021.109197
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Article: SARS-CoV-2 genomic surveillance identifies naturally occurring truncations of ORF7a that limit immune suppression.

medRxiv : the preprint server for health sciences

2021

Abstract: Over 200,000 whole genome sequences of SARS-CoV-2 have been determined for viruses isolated from around the world. These sequences have been critical for understanding the spread and evolution of SARS-CoV-2. Using global phylogenomics, we show that ... ...

Abstract	Over 200,000 whole genome sequences of SARS-CoV-2 have been determined for viruses isolated from around the world. These sequences have been critical for understanding the spread and evolution of SARS-CoV-2. Using global phylogenomics, we show that mutations frequently occur in the C-terminal end of ORF7a. We have isolated one of these mutant viruses from a patient sample and used viral challenge experiments to demonstrate that Δ115 mutation results in a growth defect. ORF7a has been implicated in immune modulation, and we show that the C-terminal truncation results in distinct changes in interferon stimulated gene expression. Collectively, this work indicates that ORF7a mutations occur frequently and that these changes affect viral mechanisms responsible for suppressing the immune response.
Language	English
Publishing date	2021-03-10
Publishing country	United States
Document type	Preprint
DOI	10.1101/2021.02.22.21252253
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Article ; Online: Severe Acute Respiratory Syndrome Coronavirus 2 Is Detected in the Gastrointestinal Tract of Asymptomatic Endoscopy Patients but Is Unlikely to Pose a Significant Risk to Healthcare Personnel.

Cherne, Michelle D / Gentry, Andrew B / Nemudraia, Anna / Nemudryi, Artem / Hedges, Jodi F / Walk, Heather / Blackwell, Karlin / Snyder, Deann T / Jerome, Maria / Madden, Wyatt / Hashimi, Marziah / Sebrell, T Andrew / King, David B / Plowright, Raina K / Jutila, Mark A / Wiedenheft, Blake / Bimczok, Diane

Gastro hep advances

2022 Volume 1, Issue 5, Page(s) 844–852

Abstract: Background and aims: Recent evidence suggests that the gut is an additional target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, whether SARS-CoV-2 spreads via gastrointestinal secretions remains unclear. To ... ...

Abstract	Background and aims: Recent evidence suggests that the gut is an additional target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, whether SARS-CoV-2 spreads via gastrointestinal secretions remains unclear. To determine the prevalence of gastrointestinal SARS-CoV-2 infection in asymptomatic subjects, we analyzed gastrointestinal biopsy and liquid samples from endoscopy patients for the presence of SARS-CoV-2. Methods: We enrolled 100 endoscopic patients without known SARS-CoV-2 infection (cohort A) and 12 patients with a previous COVID-19 diagnosis (cohort B) in a cohort study performed at a regional hospital. Gastrointestinal biopsies and fluids were screened for SARS-CoV-2 by polymerase chain reaction (PCR), immunohistochemistry, and virus isolation assay, and the stability of SARS-CoV-2 in gastrointestinal liquids in vitro was analyzed. Results: SARS-CoV-2 ribonucleic acid was detected by PCR in the colonic tissue of 1/100 patients in cohort A. In cohort B, 3 colonic liquid samples tested positive for SARS-CoV-2 by PCR and viral nucleocapsid protein was detected in the epithelium of the respective biopsy samples. However, no infectious virions were recovered from any samples. In vitro exposure of SARS-CoV-2 to colonic liquid led to a 4-log-fold reduction of infectious SARS-CoV-2 within 1 hour ( Conclusion: Overall, the persistent detection of SARS-CoV-2 in endoscopy samples after resolution of COVID-19 points to the gut as a long-term reservoir for SARS-CoV-2. Since no infectious virions were recovered and SARS-CoV-2 was rapidly inactivated in the presence of colon liquids, it is unlikely that performing endoscopic procedures is associated with a significant infection risk due to undiagnosed asymptomatic or persistent gastrointestinal SARS-CoV-2 infections.
Language	English
Publishing date	2022-06-24
Publishing country	Netherlands
Document type	Journal Article
ISSN	2772-5723
ISSN (online)	2772-5723
DOI	10.1016/j.gastha.2022.06.002
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