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Article ; Online: An HCV Vaccine on the Fly.

Laidlaw, Stephen M / Dustin, Lynn B

2019 Volume 221, Issue 8, Page(s) 1216–1218

MeSH term(s)	Hepacivirus/immunology ; Hepatitis C/prevention & control ; Humans ; Nanoparticles ; Viral Hepatitis Vaccines
Chemical Substances	Viral Hepatitis Vaccines
Language	English
Publishing date	2019-04-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiz231
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Article ; Online: TRIM21/Ro52 - Roles in Innate Immunity and Autoimmune Disease.

Jones, Esther L / Laidlaw, Stephen M / Dustin, Lynn B

Frontiers in immunology

2021 Volume 12, Page(s) 738473

Abstract: TRIM21 (Ro52/SSA1) is an E3 ubiquitin ligase with key roles in immune host defence, signal transduction, and possibly cell cycle regulation. It is also an autoantibody target in Sjögren's syndrome, systemic lupus erythematosus, and other rheumatic ... ...

Abstract	TRIM21 (Ro52/SSA1) is an E3 ubiquitin ligase with key roles in immune host defence, signal transduction, and possibly cell cycle regulation. It is also an autoantibody target in Sjögren's syndrome, systemic lupus erythematosus, and other rheumatic autoimmune diseases. Here, we summarise the structure and function of this enzyme, its roles in innate immunity, adaptive immunity and cellular homeostasis, the pathogenesis of autoimmunity against TRIM21, and the potential impacts of autoantibodies to this intracellular protein.
MeSH term(s)	Animals ; Antibodies, Antinuclear/metabolism ; Autoimmune Diseases/immunology ; Autoimmune Diseases/metabolism ; Autoimmunity ; Epitopes ; Humans ; Immunity, Innate ; Protein Conformation ; Ribonucleoproteins/immunology ; Ribonucleoproteins/metabolism ; Signal Transduction ; Structure-Activity Relationship
Chemical Substances	Antibodies, Antinuclear ; Epitopes ; Ribonucleoproteins ; SS-A antibodies ; SS-A antigen
Language	English
Publishing date	2021-09-06
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.738473
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Article: Construction of Deletion-knockout Mutant Fowlpox Virus (FWPV).

Laidlaw, Stephen M / Skinner, Michael A

Bio-protocol

2016 Volume 4, Issue 10

Abstract: The construction of deletion-knockout poxviruses is a useful approach to determining the function of specific virus genes. This protocol is an adaptation of the transient dominant knockout selection protocol published by Falkner and Moss (1990) for use ... ...

Abstract	The construction of deletion-knockout poxviruses is a useful approach to determining the function of specific virus genes. This protocol is an adaptation of the transient dominant knockout selection protocol published by Falkner and Moss (1990) for use with vaccinia virus. The protocol makes use of the dominant selectable marker
Language	English
Publishing date	2016-06-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2833269-6
ISSN	2331-8325
ISSN	2331-8325
DOI	10.21769/bioprotoc.1126
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Article ; Online: A prototype lateral flow assay for detection of orthopoxviruses.

Ulaeto, David O / Lonsdale, Steve G / Laidlaw, Stephen M / Clark, Graeme C / Horby, Peter / Carroll, Miles W

The Lancet. Infectious diseases

2022 Volume 22, Issue 9, Page(s) 1279–1280

MeSH term(s)	Biological Assay ; DNA, Viral ; Humans ; Orthopoxvirus ; Polymerase Chain Reaction
Chemical Substances	DNA, Viral
Language	English
Publishing date	2022-07-04
Publishing country	United States
Document type	Letter
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(22)00440-6
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Article: Interferon lambda: opportunities, risks, and uncertainties in the fight against HCV.

Laidlaw, Stephen M / Dustin, Lynn B

Frontiers in immunology

2014 Volume 5, Page(s) 545

Abstract: Innate immunity is key to the fight against the daily onslaught from viruses that our bodies are subjected to. Essential to this response are the interferons (IFNs) that prime our cells to block viral pathogens. Recent evidence suggests that the Type III ...

Abstract	Innate immunity is key to the fight against the daily onslaught from viruses that our bodies are subjected to. Essential to this response are the interferons (IFNs) that prime our cells to block viral pathogens. Recent evidence suggests that the Type III (λ) IFNs are intimately associated with the immune response to hepatitis C virus (HCV) infection. Genome-wide association studies have identified polymorphisms within the IFN-λ gene locus that correlate with response to IFNα-based antiviral therapy and with spontaneous clearance of HCV infection. The mechanisms for these correlations are incompletely understood. Restricted expression of the IFN-λ receptor, and the ability of IFN-λ to induce IFN-stimulated genes in HCV-infected cells, suggest potential roles for IFN-λ in HCV therapy even in this era of directly acting antivirals. This review summarizes our current understanding of the IFN-λ family and the role of λ IFNs in the natural history of HCV infection.
Keywords	covid19
Language	English
Publishing date	2014-10-31
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2014.00545
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Article ; Online: Alkyne Derivatives of SARS-CoV-2 Main Protease Inhibitors Including Nirmatrelvir Inhibit by Reacting Covalently with the Nucleophilic Cysteine.

Brewitz, Lennart / Dumjahn, Leo / Zhao, Yilin / Owen, C David / Laidlaw, Stephen M / Malla, Tika R / Nguyen, Dung / Lukacik, Petra / Salah, Eidarus / Crawshaw, Adam D / Warren, Anna J / Trincao, Jose / Strain-Damerell, Claire / Carroll, Miles W / Walsh, Martin A / Schofield, Christopher J

Journal of medicinal chemistry

2023 Volume 66, Issue 4, Page(s) 2663–2680

Abstract: Nirmatrelvir (PF-07321332) is a nitrile-bearing small-molecule inhibitor that, in combination with ritonavir, is used to treat infections by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Nirmatrelvir interrupts the viral life cycle by ... ...

Abstract	Nirmatrelvir (PF-07321332) is a nitrile-bearing small-molecule inhibitor that, in combination with ritonavir, is used to treat infections by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Nirmatrelvir interrupts the viral life cycle by inhibiting the SARS-CoV-2 main protease (M
MeSH term(s)	Humans ; Antiviral Agents/pharmacology ; COVID-19 ; Cysteine/chemistry ; Nitriles ; SARS-CoV-2/metabolism ; Viral Nonstructural Proteins/metabolism ; Viral Protease Inhibitors/pharmacology ; Coronavirus 3C Proteases
Chemical Substances	3C-like proteinase, SARS-CoV-2 (EC 3.4.22.-) ; Antiviral Agents ; Cysteine (K848JZ4886) ; Nitriles ; Viral Nonstructural Proteins ; nirmatrelvir (7R9A5P7H32) ; Viral Protease Inhibitors ; Coronavirus 3C Proteases (EC 3.4.22.28)
Language	English
Publishing date	2023-02-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.2c01627
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Article: Modulation of Early Host Innate Immune Response by an Avipox Vaccine Virus' Lateral Body Protein.

Giotis, Efstathios S / Laidlaw, Stephen M / Bidgood, Susanna R / Albrecht, David / Burden, Jemima J / Robey, Rebecca C / Mercer, Jason / Skinner, Michael A

Biomedicines

2020 Volume 8, Issue 12

Abstract: The avian pathogen fowlpox virus (FWPV) has been successfully used as a vaccine vector in poultry and humans, but relatively little is known about its ability to modulate host antiviral immune responses in these hosts, which are replication-permissive ... ...

Abstract	The avian pathogen fowlpox virus (FWPV) has been successfully used as a vaccine vector in poultry and humans, but relatively little is known about its ability to modulate host antiviral immune responses in these hosts, which are replication-permissive and nonpermissive, respectively. FWPV is highly resistant to avian type I interferon (IFN) and able to completely block the host IFN-response. Microarray screening of host IFN-regulated gene expression in cells infected with 59 different, nonessential FWPV gene knockout mutants revealed that FPV184 confers immunomodulatory capacity. We report that the
Language	English
Publishing date	2020-12-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines8120634
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Article ; Online: Immune control and failure in HCV infection--tipping the balance.

Dustin, Lynn B / Cashman, Siobhán B / Laidlaw, Stephen M

Journal of leukocyte biology

2014 Volume 96, Issue 4, Page(s) 535–548

Abstract: Despite the development of potent antiviral drugs, HCV remains a global health problem; global eradication is a long way off. In this review, we discuss the immune response to HCV infection and particularly, the interplay between viral strategies that ... ...

Abstract	Despite the development of potent antiviral drugs, HCV remains a global health problem; global eradication is a long way off. In this review, we discuss the immune response to HCV infection and particularly, the interplay between viral strategies that delay the onset of antiviral responses and host strategies that limit or even eradicate infected cells but also contribute to pathogenesis. Although HCV can disable some cellular virus-sensing machinery, IFN-stimulated antiviral genes are induced in the infected liver. Whereas epitope evolution contributes to escape from T cell-mediated immunity, chronic high antigen load may also blunt the T cell response by activating exhaustion or tolerance mechanisms. The evasive maneuvers of HCV limit sterilizing humoral immunity through rapid evolution of decoy epitopes, epitope masking, stimulation of interfering antibodies, lipid shielding, and cell-to-cell spread. Whereas the majority of HCV infections progress to chronic hepatitis with persistent viremia, at least 20% of patients spontaneously clear the infection. Most of these are protected from reinfection, suggesting that protective immunity to HCV exists and that a prophylactic vaccine may be an achievable goal. It is therefore important that we understand the correlates of protective immunity and mechanisms of viral persistence.
MeSH term(s)	B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; Gene Expression ; Hepacivirus/genetics ; Hepacivirus/immunology ; Hepacivirus/metabolism ; Hepatitis C/genetics ; Hepatitis C/immunology ; Hepatitis C/metabolism ; Hepatitis C Antibodies/immunology ; Hepatitis C, Chronic/genetics ; Hepatitis C, Chronic/immunology ; Hepatitis C, Chronic/metabolism ; Humans ; Immunity, Cellular ; Immunity, Innate ; Interferons/genetics ; Interferons/metabolism ; Killer Cells, Natural/immunology ; Killer Cells, Natural/metabolism ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism
Chemical Substances	Hepatitis C Antibodies ; Interferons (9008-11-1)
Language	English
Publishing date	2014-07-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	605722-6
ISSN	1938-3673 ; 0741-5400
ISSN (online)	1938-3673
ISSN	0741-5400
DOI	10.1189/jlb.4RI0214-126R
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Article ; Online: Convalescent plasma donors show enhanced cross-reactive neutralizing antibody response to antigenic variants of SARS-CoV-2 following immunization.

Harvala, Heli / Nguyen, Dung / Simmonds, Peter / Lamikanra, Abigail A / Tsang, Hoi Pat / Otter, Ashley / Maes, Piet / Webster, Mhairi / Clarkson, Adam / Kaloyirou, Fotini / Hopkins, Valerie / Laidlaw, Stephen M / Carroll, Miles / Mora, Ana / Griffiths, Alexandra / MacLennan, Sheila / Estcourt, Lise / Roberts, David J

Transfusion

2022 Volume 62, Issue 7, Page(s) 1347–1354

Abstract: Background: The therapeutic benefit of convalescent plasma (CP) therapy to treat COVID-19 may derive from neutralizing antibodies (nAbs) to SARS-CoV-2. To investigate the effects of antigenic variation on neutralization potency of CP, we compared nAb ... ...

Abstract	Background: The therapeutic benefit of convalescent plasma (CP) therapy to treat COVID-19 may derive from neutralizing antibodies (nAbs) to SARS-CoV-2. To investigate the effects of antigenic variation on neutralization potency of CP, we compared nAb titers against prototype and recently emerging strains of SARS-CoV-2, including Delta and Omicron, in CP donors previously infected with SARS-CoV-2 before and after immunization. Methods and materials: Samples were assayed from previously SARS-CoV-2 infected donors before (n = 17) and after one (n = 43) or two (n = 71) doses of Astra-Zeneca or Pfizer vaccinations. Ab titers against Wuhan/wild type (WT), Alpha, Beta, and Delta SARS-CoV-2 strains were determined by live virus microneutralization assay while titers to Omicron used a focus reduction neutralization test. Anti-spike antibody was assayed by Elecsys anti-SARS-CoV-2 quantitative spike assay (Roche). Results: Unvaccinated donors showed a geometric mean titer (GMT) of 148 against WT, 80 against Alpha but mostly failed to neutralize Beta, Delta, and Omicron strains. Contrastingly, high GMTs were observed in vaccinated donors against all SARS-CoV-2 strains after one vaccine dose (WT:703; Alpha:692; Beta:187; Delta:215; Omicron:434). By ROC analysis, reactivity in the Roche quantitative Elecsys spike assay of 20,000 U/mL was highly predictive of donations with nAb titers of ≥1:640 against Delta (90% sensitivity; 97% specificity) and ≥1:320 against Omicron (89% sensitivity; 81% specificity). Discussion: Vaccination of previously infected CP donors induced high levels of broadly neutralizing antibodies against circulating antigenic variants of SARS-CoV-2. High titer donations could be reliably identified by automated quantitative anti-spike antibody assay, enabling large-scale preselection of high-titer convalescent plasma.
MeSH term(s)	Antibodies, Neutralizing ; Antibodies, Viral ; Antigenic Variation ; COVID-19/therapy ; Humans ; Immunization ; Immunization, Passive ; SARS-CoV-2 ; Vaccination
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral
Language	English
Publishing date	2022-06-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208417-x
ISSN	1537-2995 ; 0041-1132
ISSN (online)	1537-2995
ISSN	0041-1132
DOI	10.1111/trf.16934
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Article ; Online: Obesity Differs from Diabetes Mellitus in Antibody and T Cell Responses Post COVID-19 Recovery.

Ali, Mohammad / Longet, Stephanie / Neale, Isabel / Rongkard, Patpong / Chowdhury, Forhad Uddin Hassan / Hill, Jennifer / Brown, Anthony / Laidlaw, Stephen / Tipton, Tom / Hoque, Ashraful / Hassan, Nazia / Hackstein, Carl-Philipp / Adele, Sandra / Akther, Hossain Delowar / Abraham, Priyanka / Paul, Shrebash / Rahman, Md Matiur / Alam, Md Masum / Parvin, Shamima /

Hoque Mollah, Forhadul / Hoque, Md Mozammel / Moore, Shona C / Biswas, Subrata K / Turtle, Lance / de Silva, Thushan I / Ogbe, Ane / Frater, John / Barnes, Eleanor / Tomic, Adriana / Carroll, Miles W / Klenerman, Paul / Kronsteiner, Barbara / Chowdhury, Fazle Rabbi / Dunachie, Susanna J

Clinical and experimental immunology

2024

Abstract: Obesity and type 2 diabetes (DM) are risk factors for severe COVID-19 outcomes, which disproportionately affect South Asian populations. This study aims to investigate the humoral and cellular immune responses to SARS-CoV-2 in adult COVID-19 survivors ... ...

Abstract	Obesity and type 2 diabetes (DM) are risk factors for severe COVID-19 outcomes, which disproportionately affect South Asian populations. This study aims to investigate the humoral and cellular immune responses to SARS-CoV-2 in adult COVID-19 survivors with obesity and DM in Bangladesh. In this cross-sectional study, SARS-CoV-2-specific antibody and T cell responses were investigated in 63 healthy and 75 PCR-confirmed COVID-19 recovered individuals in Bangladesh, during the pre-vaccination first wave of the COVID-19 pandemic in 2020. In COVID-19 survivors, SARS-CoV-2 infection induced robust antibody and T cell responses, which correlated with disease severity. After adjusting for age, sex, DM status, disease severity, and time since onset of symptoms, obesity was associated with decreased neutralising antibody titers, and increased SARS-CoV-2 spike-specific IFN-γ response along with increased proliferation and IL-2 production by CD8+ T cells. In contrast, DM was not associated with SARS-CoV-2-specific antibody and T cell responses after adjustment for obesity and other confounders. Obesity is associated with lower neutralising antibody levels and higher T cell responses to SARS-CoV-2 post COVID-19 recovery, while antibody or T cell responses remain unaltered in DM.
Language	English
Publishing date	2024-04-20
Publishing country	England
Document type	Journal Article
ZDB-ID	218531-3
ISSN	1365-2249 ; 0009-9104 ; 0964-2536
ISSN (online)	1365-2249
ISSN	0009-9104 ; 0964-2536
DOI	10.1093/cei/uxae030
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