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Article ; Online: Ankyrin G organizes membrane components to promote coupling of cell mechanics and glucose uptake.

Salvi, Alicia M / Bays, Jennifer L / Mackin, Samantha R / Mege, René-Marc / DeMali, Kris A

2021 Volume 23, Issue 5, Page(s) 457–466

Abstract: The response of cells to forces is critical for their function and occurs via rearrangement of the actin ... ...

Abstract	The response of cells to forces is critical for their function and occurs via rearrangement of the actin cytoskeleton
MeSH term(s)	Ankyrins/metabolism ; Biological Transport/physiology ; Carrier Proteins/metabolism ; Cell Membrane/metabolism ; Cytoskeleton/metabolism ; Glucose/metabolism ; Glucose Transporter Type 1/metabolism ; Humans ; Signal Transduction/physiology
Chemical Substances	Ankyrins ; Carrier Proteins ; Glucose Transporter Type 1 ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2021-05-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1474722-4
ISSN	1476-4679 ; 1465-7392
ISSN (online)	1476-4679
ISSN	1465-7392
DOI	10.1038/s41556-021-00677-y
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Article ; Online: Fc-γR-dependent antibody effector functions are required for vaccine-mediated protection against antigen-shifted variants of SARS-CoV-2.

Mackin, Samantha R / Desai, Pritesh / Whitener, Bradley M / Karl, Courtney E / Liu, Meizi / Baric, Ralph S / Edwards, Darin K / Chicz, Taras M / McNamara, Ryan P / Alter, Galit / Diamond, Michael S

Nature microbiology

2023 Volume 8, Issue 4, Page(s) 569–580

Abstract: Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with antigenic changes in the spike protein are neutralized less efficiently by serum antibodies elicited by legacy vaccines against the ancestral Wuhan-1 virus. Nonetheless, ... ...

Abstract	Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with antigenic changes in the spike protein are neutralized less efficiently by serum antibodies elicited by legacy vaccines against the ancestral Wuhan-1 virus. Nonetheless, these vaccines, including mRNA-1273 and BNT162b2, retained their ability to protect against severe disease and death, suggesting that other aspects of immunity control infection in the lung. Vaccine-elicited antibodies can bind Fc gamma receptors (FcγRs) and mediate effector functions against SARS-CoV-2 variants, and this property correlates with improved clinical coronavirus disease 2019 outcome. However, a causal relationship between Fc effector functions and vaccine-mediated protection against infection has not been established. Here, using passive and active immunization approaches in wild-type and FcγR-knockout mice, we determined the requirement for Fc effector functions to control SARS-CoV-2 infection. The antiviral activity of passively transferred immune serum was lost against multiple SARS-CoV-2 strains in mice lacking expression of activating FcγRs, especially murine FcγR III (CD16), or depleted of alveolar macrophages. After immunization with the pre-clinical mRNA-1273 vaccine, control of Omicron BA.5 infection in the respiratory tract also was lost in mice lacking FcγR III. Our passive and active immunization studies in mice suggest that Fc-FcγR engagement and alveolar macrophages are required for vaccine-induced antibody-mediated protection against infection by antigenically changed SARS-CoV-2 variants, including Omicron strains.
MeSH term(s)	Animals ; Humans ; Mice ; SARS-CoV-2/genetics ; 2019-nCoV Vaccine mRNA-1273 ; Receptors, IgG/genetics ; BNT162 Vaccine ; COVID-19/prevention & control ; Vaccines ; Antibodies, Viral ; Mice, Knockout
Chemical Substances	2019-nCoV Vaccine mRNA-1273 (EPK39PL4R4) ; Receptors, IgG ; BNT162 Vaccine ; Vaccines ; Antibodies, Viral
Language	English
Publishing date	2023-04-03
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2058-5276
ISSN (online)	2058-5276
DOI	10.1038/s41564-023-01359-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Murine Coronavirus Infection Activates the Aryl Hydrocarbon Receptor in an Indoleamine 2,3-Dioxygenase-Independent Manner, Contributing to Cytokine Modulation and Proviral TCDD-Inducible-PARP Expression.

Grunewald, Matthew E / Shaban, Mohamed G / Mackin, Samantha R / Fehr, Anthony R / Perlman, Stanley

Journal of virology

2020 Volume 94, Issue 3

Abstract: The aryl hydrocarbon receptor (AhR) is a cytoplasmic receptor/transcription factor that modulates several cellular and immunological processes following activation by pathogen-associated stimuli, though its role during virus infection is largely unknown. ...

Abstract	The aryl hydrocarbon receptor (AhR) is a cytoplasmic receptor/transcription factor that modulates several cellular and immunological processes following activation by pathogen-associated stimuli, though its role during virus infection is largely unknown. Here, we show that AhR is activated in cells infected with mouse hepatitis virus (MHV), a coronavirus (CoV), and contributes to the upregulation of downstream effector TCDD-inducible poly(ADP-ribose) polymerase (TiPARP) during infection. Knockdown of TiPARP reduced viral replication and increased interferon expression, suggesting that TiPARP functions in a proviral manner during MHV infection. We also show that MHV replication induced the expression of other genes known to be downstream of AhR in macrophages and dendritic cells and in livers of infected mice. Further, we found that chemically inhibiting or activating AhR reciprocally modulated the expression levels of cytokines induced by infection, specifically, interleukin 1β (IL-1β), IL-10, and tumor necrosis factor alpha (TNF-α), consistent with a role for AhR activation in the host response to MHV infection. Furthermore, while indoleamine 2,3-dioxygenase (IDO1) drives AhR activation in other settings, MHV infection induced equal expression of downstream genes in wild-type (WT) and IDO1
MeSH term(s)	Animals ; Cytokines/genetics ; Cytokines/metabolism ; Gene Expression Regulation, Enzymologic ; Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism ; Mice ; Mice, Knockout ; Murine hepatitis virus/physiology ; Poly(ADP-ribose) Polymerases/biosynthesis ; Poly(ADP-ribose) Polymerases/genetics ; Proviruses/physiology ; Receptors, Aryl Hydrocarbon/genetics ; Receptors, Aryl Hydrocarbon/metabolism ; Signal Transduction ; Virus Replication/physiology
Chemical Substances	Cytokines ; IDO1 protein, mouse ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; Receptors, Aryl Hydrocarbon ; 2,3,7,8-tetrachlorodibenzo-p-dioxin poly(ADP-ribose) polymerase, mouse (EC 2.4.2.30) ; Poly(ADP-ribose) Polymerases (EC 2.4.2.30)
Keywords	covid19
Language	English
Publishing date	2020-01-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.01743-19
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Article: Fcγ receptor-dependent antibody effector functions are required for vaccine protection against infection by antigenic variants of SARS-CoV-2.

Mackin, Samantha R / Desai, Pritesh / Whitener, Bradley M / Karl, Courtney E / Liu, Meizi / Baric, Ralph S / Edwards, Darin K / Chicz, Taras M / McNamara, Ryan P / Alter, Galit / Diamond, Michael S

bioRxiv : the preprint server for biology

2022

Abstract: Emerging SARS-CoV-2 variants with antigenic changes in the spike protein are neutralized less efficiently by serum antibodies elicited by legacy vaccines against the ancestral Wuhan-1 virus. Nonetheless, these vaccines, including mRNA-1273 and BNT162b2, ... ...

Abstract	Emerging SARS-CoV-2 variants with antigenic changes in the spike protein are neutralized less efficiently by serum antibodies elicited by legacy vaccines against the ancestral Wuhan-1 virus. Nonetheless, these vaccines, including mRNA-1273 and BNT162b2, retained their ability to protect against severe disease and death, suggesting that other aspects of immunity control infection in the lung. Although vaccine-elicited antibodies can bind Fc gamma receptors (FcγRs) and mediate effector functions against SARS-CoV-2 variants, and this property correlates with improved clinical COVID-19 outcome, a causal relationship between Fc effector functions and vaccine-mediated protection against infection has not been established. Here, using passive and active immunization approaches in wild-type and Fc-gamma receptor (FcγR) KO mice, we determined the requirement for Fc effector functions to protect against SARS-CoV-2 infection. The antiviral activity of passively transferred immune serum was lost against multiple SARS-CoV-2 strains in mice lacking expression of activating FcγRs, especially murine FcγR III (CD16), or depleted of alveolar macrophages. After immunization with the preclinical mRNA-1273 vaccine, protection against Omicron BA.5 infection in the respiratory tract also was lost in mice lacking FcγR III. Our passive and active immunization studies in mice suggest that Fc-FcγR engagement and alveolar macrophages are required for vaccine-induced antibody-mediated protection against infection by antigenically changed SARS-CoV-2 variants, including Omicron strains.
Language	English
Publishing date	2022-11-28
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.11.27.518117
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Article ; Online: Immunoglobulin replacement products protect against SARS-CoV-2 infection in vivo despite poor neutralizing activity.

Zimmerman, Ofer / Altman Doss, Alexa Michelle / Ying, Baoling / Liang, Chieh-Yu / Mackin, Samantha R / Davis-Adams, Hannah G / Adams, Lucas J / VanBlargan, Laura A / Chen, Rita E / Scheaffer, Suzanne M / Desai, Pritesh / Raju, Saravanan / Mantia, Tarisa L / O'Shaughnessy, Caitlin C / Monroy, Jennifer Marie / Wedner, H James / Rigell, Christopher J / Kau, Andrew L / Dy, Tiffany Biason /

Ren, Zhen / Turner, Jackson S / O'Halloran, Jane A / Presti, Rachel M / Kendall, Peggy L / Fremont, Daved H / Ellebedy, Ali H / Diamond, Michael S

JCI insight

2024 Volume 9, Issue 3

Abstract: Immunoglobulin (IG) replacement products are used routinely in patients with immune deficiency and other immune dysregulation disorders who have poor responses to vaccination and require passive immunity conferred by commercial antibody products. The ... ...

Abstract	Immunoglobulin (IG) replacement products are used routinely in patients with immune deficiency and other immune dysregulation disorders who have poor responses to vaccination and require passive immunity conferred by commercial antibody products. The binding, neutralizing, and protective activity of intravenously administered IG against SARS-CoV-2 emerging variants remains unknown. Here, we tested 198 different IG products manufactured from December 2019 to August 2022. We show that prepandemic IG had no appreciable cross-reactivity or neutralizing activity against SARS-CoV-2. Anti-spike antibody titers and neutralizing activity against SARS-CoV-2 WA1/2020 D614G increased gradually after the pandemic started and reached levels comparable to vaccinated healthy donors 18 months after the diagnosis of the first COVID-19 case in the United States in January 2020. The average time between production to infusion of IG products was 8 months, which resulted in poor neutralization of the variant strain circulating at the time of infusion. Despite limited neutralizing activity, IG prophylaxis with clinically relevant dosing protected susceptible K18-hACE2-transgenic mice against clinical disease, lung infection, and lung inflammation caused by the XBB.1.5 Omicron variant. Moreover, following IG prophylaxis, levels of XBB.1.5 infection in the lung were higher in FcγR-KO mice than in WT mice. Thus, IG replacement products with poor neutralizing activity against evolving SARS-CoV-2 variants likely confer protection to patients with immune deficiency disorders through Fc effector function mechanisms.
MeSH term(s)	Humans ; Animals ; Mice ; COVID-19/prevention & control ; SARS-CoV-2 ; Antibodies ; Cross Reactions ; Mice, Transgenic
Chemical Substances	Antibodies
Language	English
Publishing date	2024-02-08
Publishing country	United States
Document type	Journal Article
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.176359
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Article ; Online: Fc-gamma receptor-dependent antibody effector functions are required for vaccine protection against infection by antigenic variants of SARS-CoV-2

Mackin, Samantha R. / Desai, Pritesh / Whitener, Bradley M. / Karl, Courtney E. / Liu, Meizi / Baric, Ralph S. / Edwards, Darin K. / Chicz, Taras M. / McNamara, Ryan P. / Alter, Galit / Diamond, Michael S.

bioRxiv

Abstract	Emerging SARS-CoV-2 variants with antigenic changes in the spike protein are neutralized less efficiently by serum antibodies elicited by legacy vaccines against the ancestral Wuhan-1 virus. Nonetheless, these vaccines, including mRNA-1273 and BNT162b2, retained their ability to protect against severe disease and death, suggesting that other aspects of immunity control infection in the lung. Although vaccine-elicited antibodies can bind Fc gamma receptors and mediate effector functions against SARS-CoV-2 variants, and this property correlates with improved clinical COVID-19 outcome, a causal relationship between Fc effector functions and vaccine-mediated protection against infection has not been established. Here, using passive and active immunization approaches in wild-type and Fc-gamma receptor (FcgR) KO mice, we determined the requirement for Fc effector functions to protect against SARS-CoV-2 infection. The antiviral activity of passively transferred immune serum was lost against multiple SARS-CoV-2 strains in mice lacking expression of activating FcgRs, especially murine FcgR III (CD16), or depleted of alveolar macrophages. After immunization with the preclinical mRNA-1273 vaccine, protection against Omicron BA.5 infection in the respiratory tract also was lost in mice lacking FcgR III. Our passive and active immunization studies in mice suggest that Fc-FcgR engagement and alveolar macrophages are required for vaccine-induced antibody-mediated protection against infection by antigenically changed SARS-CoV-2 variants, including Omicron strains.
Keywords	covid19
Language	English
Publishing date	2022-11-29
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2022.11.27.518117
Database	COVID19

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Article ; Online: Inactivation of Severe Acute Respiratory Coronavirus Virus 2 (SARS-CoV-2) and Diverse RNA and DNA Viruses on Three-Dimensionally Printed Surgical Mask Materials.

Welch, Jennifer L / Xiang, Jinhua / Mackin, Samantha R / Perlman, Stanley / Thorne, Peter / O'Shaughnessy, Patrick / Strzelecki, Brian / Aubin, Patrick / Ortiz-Hernandez, Monica / Stapleton, Jack T

Infection control and hospital epidemiology

2020 Volume 42, Issue 3, Page(s) 253–260

Abstract: Background: Personal protective equipment (PPE) is a critical need during the coronavirus disease 2019 (COVID-19) pandemic. Alternative sources of surgical masks, including 3-dimensionally (3D) printed approaches that may be reused, are urgently needed ... ...

Abstract	Background: Personal protective equipment (PPE) is a critical need during the coronavirus disease 2019 (COVID-19) pandemic. Alternative sources of surgical masks, including 3-dimensionally (3D) printed approaches that may be reused, are urgently needed to prevent PPE shortages. Few data exist identifying decontamination strategies to inactivate viral pathogens and retain 3D-printing material integrity. Objective: To test viral disinfection methods on 3D-printing materials. Methods: The viricidal activity of common disinfectants (10% bleach, quaternary ammonium sanitizer, 3% hydrogen peroxide, or 70% isopropanol and exposure to heat (50°C, and 70°C) were tested on four 3D-printed materials used in the healthcare setting, including a surgical mask design developed by the Veterans' Health Administration. Inactivation was assessed for several clinically relevant RNA and DNA pathogenic viruses, including severe acute respiratory coronavirus virus 2 (SARS-CoV-2) and human immunodeficiency virus 1 (HIV-1). Results: SARS-CoV-2 and all viruses tested were completely inactivated by a single application of bleach, ammonium quaternary compounds, or hydrogen peroxide. Similarly, exposure to dry heat (70°C) for 30 minutes completely inactivated all viruses tested. In contrast, 70% isopropanol reduced viral titers significantly less well following a single application. Inactivation did not interfere with material integrity of the 3D-printed materials. Conclusions: Several standard decontamination approaches effectively disinfected 3D-printed materials. These approaches were effective in the inactivation SARS-CoV-2, its surrogates, and other clinically relevant viral pathogens. The decontamination of 3D-printed surgical mask materials may be useful during crisis situations in which surgical mask supplies are limited.
MeSH term(s)	2-Propanol ; COVID-19/prevention & control ; DNA, Viral/drug effects ; Decontamination/methods ; Disinfectants/pharmacology ; Disinfection/methods ; HIV-1/drug effects ; Healthy Volunteers ; Hot Temperature ; Humans ; Hydrogen Peroxide ; Masks ; Personal Protective Equipment ; Printing, Three-Dimensional ; RNA, Viral/drug effects ; SARS-CoV-2/drug effects ; Virus Diseases/prevention & control ; Virus Inactivation
Chemical Substances	DNA, Viral ; Disinfectants ; RNA, Viral ; Hydrogen Peroxide (BBX060AN9V) ; 2-Propanol (ND2M416302)
Keywords	covid19
Language	English
Publishing date	2020-08-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639378-0
ISSN	1559-6834 ; 0195-9417 ; 0899-823X
ISSN (online)	1559-6834
ISSN	0195-9417 ; 0899-823X
DOI	10.1017/ice.2020.417
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Article: Inactivation of Severe Acute Respiratory Coronavirus Virus 2 (SARS-CoV-2) and Diverse RNA and DNA Viruses on Three-Dimensionally Printed Surgical Mask Materials

Welch, Jennifer L / Xiang, Jinhua / Mackin, Samantha R / Perlman, Stanley / Thorne, Peter / O039, / Shaughnessy, Patrick / Strzelecki, Brian / Aubin, Patrick / Ortiz-Hernandez, Monica / Stapleton, Jack T

Infect Control Hosp Epidemiol

Abstract: BACKGROUND: Personal protective equipment (PPE) is a critical need during the coronavirus disease 2019 (COVID-19) pandemic. Alternative sources of surgical masks, including 3-dimensionally (3D) printed approaches that may be reused, are urgently needed ... ...

Abstract	BACKGROUND: Personal protective equipment (PPE) is a critical need during the coronavirus disease 2019 (COVID-19) pandemic. Alternative sources of surgical masks, including 3-dimensionally (3D) printed approaches that may be reused, are urgently needed to prevent PPE shortages. Few data exist identifying decontamination strategies to inactivate viral pathogens and retain 3D-printing material integrity. OBJECTIVE: To test viral disinfection methods on 3D-printing materials. METHODS: The viricidal activity of common disinfectants (10% bleach, quaternary ammonium sanitizer, 3% hydrogen peroxide, or 70% isopropanol and exposure to heat (50°C, and 70°C) were tested on four 3D-printed materials used in the healthcare setting, including a surgical mask design developed by the Veterans' Health Administration. Inactivation was assessed for several clinically relevant RNA and DNA pathogenic viruses, including severe acute respiratory coronavirus virus 2 (SARS-CoV-2) and human immunodeficiency virus 1 (HIV-1). RESULTS: SARS-CoV-2 and all viruses tested were completely inactivated by a single application of bleach, ammonium quaternary compounds, or hydrogen peroxide. Similarly, exposure to dry heat (70°C) for 30 minutes completely inactivated all viruses tested. In contrast, 70% isopropanol reduced viral titers significantly less well following a single application. Inactivation did not interfere with material integrity of the 3D-printed materials. CONCLUSIONS: Several standard decontamination approaches effectively disinfected 3D-printed materials. These approaches were effective in the inactivation SARS-CoV-2, its surrogates, and other clinically relevant viral pathogens. The decontamination of 3D-printed surgical mask materials may be useful during crisis situations in which surgical mask supplies are limited.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #714439
Database	COVID19

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Article ; Online: Inactivation of Severe Acute Respiratory Coronavirus Virus 2 (SARS-CoV-2) and Diverse RNA and DNA Viruses on Three-Dimensionally Printed Surgical Mask Materials

Welch, Jennifer L. / Xiang, Jinhua / Mackin, Samantha R. / Perlman, Stanley / Thorne, Peter / O’Shaughnessy, Patrick / Strzelecki, Brian / Aubin, Patrick / Ortiz-Hernandez, Monica / Stapleton, Jack T.

Infection Control & Hospital Epidemiology

2020 , Page(s) 1–8

Abstract: Abstract Background: Personal protective equipment (PPE) is a critical need during the coronavirus disease 2019 (COVID-19) pandemic. Alternative sources of surgical masks, including 3-dimensionally (3D) printed approaches that may be reused, are urgently ...

Abstract	Abstract Background: Personal protective equipment (PPE) is a critical need during the coronavirus disease 2019 (COVID-19) pandemic. Alternative sources of surgical masks, including 3-dimensionally (3D) printed approaches that may be reused, are urgently needed to prevent PPE shortages. Few data exist identifying decontamination strategies to inactivate viral pathogens and retain 3D-printing material integrity. Objective: To test viral disinfection methods on 3D-printing materials. Methods: The viricidal activity of common disinfectants (10% bleach, quaternary ammonium sanitizer, 3% hydrogen peroxide, or 70% isopropanol and exposure to heat (50°C, and 70°C) were tested on four 3D-printed materials used in the healthcare setting, including a surgical mask design developed by the Veterans’ Health Administration. Inactivation was assessed for several clinically relevant RNA and DNA pathogenic viruses, including severe acute respiratory coronavirus virus 2 (SARS-CoV-2) and human immunodeficiency virus 1 (HIV-1). Results: SARS-CoV-2 and all viruses tested were completely inactivated by a single application of bleach, ammonium quaternary compounds, or hydrogen peroxide. Similarly, exposure to dry heat (70°C) for 30 minutes completely inactivated all viruses tested. In contrast, 70% isopropanol reduced viral titers significantly less well following a single application. Inactivation did not interfere with material integrity of the 3D-printed materials. Conclusions: Several standard decontamination approaches effectively disinfected 3D-printed materials. These approaches were effective in the inactivation SARS-CoV-2, its surrogates, and other clinically relevant viral pathogens. The decontamination of 3D-printed surgical mask materials may be useful during crisis situations in which surgical mask supplies are limited.
Keywords	Microbiology (medical) ; Epidemiology ; Infectious Diseases ; covid19
Language	English
Publisher	Cambridge University Press (CUP)
Publishing country	uk
Document type	Article ; Online
ZDB-ID	639378-0
ISSN	1559-6834 ; 0195-9417 ; 0899-823X
ISSN (online)	1559-6834
ISSN	0195-9417 ; 0899-823X
DOI	10.1017/ice.2020.417
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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