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Article ; Online: Persistent COVID-19 Infection in Wiskott-Aldrich Syndrome Cleared Following Therapeutic Vaccination: a Case Report.

Bradley, Rachel E / Ponsford, Mark J / Scurr, Martin J / Godkin, Andrew / Jolles, Stephen

2021 Volume 42, Issue 1, Page(s) 32–35

MeSH term(s)	Adult ; COVID-19/immunology ; Humans ; Male ; SARS-CoV-2/immunology ; Vaccination/methods ; Wiskott-Aldrich Syndrome/immunology ; Wiskott-Aldrich Syndrome Protein/immunology
Chemical Substances	Wiskott-Aldrich Syndrome Protein
Language	English
Publishing date	2021-10-29
Publishing country	Netherlands
Document type	Case Reports ; Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	779361-3
ISSN	1573-2592 ; 0271-9142
ISSN (online)	1573-2592
ISSN	0271-9142
DOI	10.1007/s10875-021-01158-5
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Article ; Online: Prognostic significance of interleukin-17A-producing colorectal tumour antigen-specific T cells.

Thomson, Amanda / Bento, Diana F Costa / Scurr, Martin J / Smart, Kathryn / Somerville, Michelle S / Keita, Åsa V / Gallimore, Awen / Godkin, Andrew

British journal of cancer

2021 Volume 124, Issue 9, Page(s) 1552–1555

Abstract: Background: The T cell cytokine profile is a key prognostic indicator of post-surgical outcome for colorectal cancer (CRC). Whilst T: Methods: We sought to determine the cytokine profile of circulating tumour antigen-(5T4/CEA) specific T cells of 34 ... ...

Abstract	Background: The T cell cytokine profile is a key prognostic indicator of post-surgical outcome for colorectal cancer (CRC). Whilst T Methods: We sought to determine the cytokine profile of circulating tumour antigen-(5T4/CEA) specific T cells of 34 CRC patients to address whether antigen-specific IL-17A responses were detectable and whether these were distinct to IFN-γ responses. Results: As with IFN-γ-producing T cells, anti-5T4/CEA T Conclusions: Tumour antigen-specific T
MeSH term(s)	Antigens, Neoplasm/immunology ; Case-Control Studies ; Colorectal Neoplasms/immunology ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/surgery ; Colorectal Surgery/mortality ; Female ; Follow-Up Studies ; Humans ; Interferon-gamma/metabolism ; Interleukin-17/immunology ; Male ; Middle Aged ; Neoplasm Recurrence, Local/immunology ; Neoplasm Recurrence, Local/pathology ; Neoplasm Recurrence, Local/surgery ; Prognosis ; Survival Rate ; Th1 Cells/immunology
Chemical Substances	Antigens, Neoplasm ; IL17A protein, human ; Interleukin-17 ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2021-03-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-021-01283-3
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Article ; Online: Magnitude of venous or capillary blood-derived SARS-CoV-2-specific T cell response determines COVID-19 immunity.

Scurr, Martin J / Lippiatt, George / Capitani, Lorenzo / Bentley, Kirsten / Lauder, Sarah N / Smart, Kathryn / Somerville, Michelle S / Rees, Tara / Stanton, Richard J / Gallimore, Awen / Hindley, James P / Godkin, Andrew

Nature communications

2022 Volume 13, Issue 1, Page(s) 5422

Abstract: T cells specific for SARS-CoV-2 are thought to protect against infection and development of COVID-19, but direct evidence for this is lacking. Here, we associated whole-blood-based measurement of SARS-CoV-2-specific interferon-γ-positive T cell responses ...

Abstract	T cells specific for SARS-CoV-2 are thought to protect against infection and development of COVID-19, but direct evidence for this is lacking. Here, we associated whole-blood-based measurement of SARS-CoV-2-specific interferon-γ-positive T cell responses with positive COVID-19 diagnostic (PCR and/or lateral flow) test results up to 6 months post-blood sampling. Amongst 148 participants donating venous blood samples, SARS-CoV-2-specific T cell response magnitude is significantly greater in those who remain protected versus those who become infected (P < 0.0001); relatively low magnitude T cell response results in a 43.2% risk of infection, whereas high magnitude reduces this risk to 5.4%. These findings are recapitulated in a further 299 participants testing a scalable capillary blood-based assay that could facilitate the acquisition of population-scale T cell immunity data (14.9% and 4.4%, respectively). Hence, measurement of SARS-CoV-2-specific T cells can prognosticate infection risk and should be assessed when monitoring individual and population immunity status.
MeSH term(s)	Antibodies, Viral ; COVID-19 ; Humans ; Interferon-gamma ; Polymerase Chain Reaction ; SARS-CoV-2 ; T-Lymphocytes
Chemical Substances	Antibodies, Viral ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2022-09-21
Publishing country	England
Document type	Journal Article ; 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/s41467-022-32985-8
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Article ; Online: Response to COVID-19 booster vaccinations in seronegative people with multiple sclerosis.

Tallantyre, Emma C / Scurr, Martin J / Vickaryous, Nicola / Richards, Aidan / Anderson, Valerie / Baker, David / Chance, Randy / Evangelou, Nikos / George, Katila / Giovannoni, Gavin / Harding, Katharine E / Hibbert, Aimee / Ingram, Gillian / Jolles, Stephen / Jones, Meleri / Kang, Angray S / Loveless, Samantha / Moat, Stuart J / Robertson, Neil P /

Rios, Francesca / Schmierer, Klaus / Willis, Mark / Godkin, Andrew / Dobson, Ruth

Multiple sclerosis and related disorders

2022 Volume 64, Page(s) 103937

Abstract: Background: People with MS treated with anti-CD20 therapies and fingolimod often have attenuated responses to initial COVID-19 vaccination. However, uncertainties remain about the benefit of a 3rd (booster) COVID-19 vaccine in this group.: Methods: ... ...

Abstract	Background: People with MS treated with anti-CD20 therapies and fingolimod often have attenuated responses to initial COVID-19 vaccination. However, uncertainties remain about the benefit of a 3rd (booster) COVID-19 vaccine in this group. Methods: PwMS without a detectable IgG response following COVID-19 vaccines 1&2 were invited to participate. Participants provided a dried blood spot +/- venous blood sample 2-12 weeks following COVID-19 vaccine 3. Humoral and T cell responses to SARS-CoV-2 spike protein and nucleocapsid antigen were measured. Results: Of 81 participants, 79 provided a dried blood spot sample, of whom 38 also provided a whole blood sample; 2 provided only whole blood. Anti-SARS-CoV-2-spike IgG seroconversion post-COVID-19 vaccine 3 occurred in 26/79 (33%) participants; 26/40 (65%) had positive T-cell responses. Overall, 31/40 (78%) demonstrated either humoral or cellular immune response post-COVID-19 vaccine 3. There was no association between laboratory evidence of prior COVID-19 and seroconversion following vaccine 3. Conclusions: Approximately one third of pwMS who were seronegative after initial COVID-19 vaccination seroconverted after booster (third) vaccination, supporting the use of boosters in this group. Almost 8 out of 10 had a measurable immune response following 3rd COVID-19 vaccine.
MeSH term(s)	Antibodies, Viral ; COVID-19/prevention & control ; COVID-19 Vaccines ; Humans ; Immunoglobulin G ; Multiple Sclerosis/drug therapy ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Vaccination
Chemical Substances	Antibodies, Viral ; COVID-19 Vaccines ; Immunoglobulin G ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2022-06-04
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2645330-7
ISSN	2211-0356 ; 2211-0348
ISSN (online)	2211-0356
ISSN	2211-0348
DOI	10.1016/j.msard.2022.103937
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Article ; Online: The Ussing chamber system for measuring intestinal permeability in health and disease.

Thomson, Amanda / Smart, Kathryn / Somerville, Michelle S / Lauder, Sarah N / Appanna, Gautham / Horwood, James / Sunder Raj, Lawrence / Srivastava, Brijesh / Durai, Dharmaraj / Scurr, Martin J / Keita, Åsa V / Gallimore, Awen M / Godkin, Andrew

BMC gastroenterology

2019 Volume 19, Issue 1, Page(s) 98

Abstract: Background: The relationship between intestinal epithelial integrity and the development of intestinal disease is of increasing interest. A reduction in mucosal integrity has been associated with ulcerative colitis, Crohn's disease and potentially could ...

Abstract	Background: The relationship between intestinal epithelial integrity and the development of intestinal disease is of increasing interest. A reduction in mucosal integrity has been associated with ulcerative colitis, Crohn's disease and potentially could have links with colorectal cancer development. The Ussing chamber system can be utilised as a valuable tool for measuring gut integrity. Here we describe step-by-step methodology required to measure intestinal permeability of both mouse and human colonic tissue samples ex vivo, using the latest equipment and software. This system can be modified to accommodate other tissues. Methods: An Ussing chamber was constructed and adapted to support both mouse and human tissue to measure intestinal permeability, using paracellular flux and electrical measurements. Two mouse models of intestinal inflammation (dextran sodium sulphate treatment and T regulatory cell depletion using C57BL/6-FoxP3 Results: Distinct regional differences in permeability were consistently identified within mouse and healthy human colon. In particular, mice showed increased permeability in the mid colonic region. In humans the left colon is more permeable than the right. Furthermore, inflammatory conditions induced chemically or due to autoimmunity reduced intestinal integrity, validating the use of the system. Conclusions: The Ussing chamber has been used for many years to measure barrier function. However, a clear and informative methods paper describing the setup of modern equipment and step-by-step procedure to measure mouse and human intestinal permeability isn't available. The Ussing chamber system methodology we describe provides such detail to guide investigation of gut integrity.
MeSH term(s)	Animals ; Colitis/chemically induced ; Colitis/metabolism ; Colon/metabolism ; Dextran Sulfate ; Electrodiagnosis/instrumentation ; Electrodiagnosis/methods ; Fluorescence ; Humans ; Intestinal Mucosa/metabolism ; Mice ; Mice, Inbred C57BL ; Permeability
Chemical Substances	Dextran Sulfate (9042-14-2)
Language	English
Publishing date	2019-06-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2041351-8
ISSN	1471-230X ; 1471-230X
ISSN (online)	1471-230X
ISSN	1471-230X
DOI	10.1186/s12876-019-1002-4
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Article ; Online: Whole blood-based measurement of SARS-CoV-2-specific T cells reveals asymptomatic infection and vaccine immunogenicity in healthy subjects and patients with solid-organ cancers.

Immunology

2021 Volume 165, Issue 2, Page(s) 250–259

Abstract: Accurate assessment of SARS-CoV-2 immunity is critical in evaluating vaccine efficacy and devising public health policies. Whilst the exact nature of effective immunity remains incompletely defined, SARS-CoV-2-specific T-cell responses are a critical ... ...

Abstract	Accurate assessment of SARS-CoV-2 immunity is critical in evaluating vaccine efficacy and devising public health policies. Whilst the exact nature of effective immunity remains incompletely defined, SARS-CoV-2-specific T-cell responses are a critical feature that will likely form a key correlate of protection against COVID-19. Here, we developed and optimized a high-throughput whole blood-based assay to determine the T-cell response associated with prior SARS-CoV-2 infection and/or vaccination amongst 231 healthy donors and 68 cancer patients. Following overnight in vitro stimulation with SARS-CoV-2-specific peptides, blood plasma samples were analysed for T
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; COVID-19/immunology ; COVID-19/prevention & control ; COVID-19 Vaccines/immunology ; Carrier State/immunology ; Female ; Humans ; Immunity, Cellular ; Immunogenicity, Vaccine ; Interferon-gamma/immunology ; Male ; Middle Aged ; SARS-CoV-2/immunology ; Th1 Cells/immunology ; Vaccination
Chemical Substances	COVID-19 Vaccines ; IFNG protein, human ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2021-12-06
Publishing country	England
Document type	Clinical Trial ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	80124-0
ISSN	1365-2567 ; 0019-2805 ; 0953-4954
ISSN (online)	1365-2567
ISSN	0019-2805 ; 0953-4954
DOI	10.1111/imm.13433
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Article ; Online: The nature of the human T cell response to the cancer antigen 5T4 is determined by the balance of regulatory and inflammatory T cells of the same antigen-specificity: implications for vaccine design.

Besneux, Matthieu / Greenshields-Watson, Alexander / Scurr, Martin J / MacLachlan, Bruce J / Christian, Adam / Davies, Michael M / Hargest, Rachel / Phillips, Simon / Godkin, Andrew / Gallimore, Awen

Cancer immunology, immunotherapy : CII

2018 Volume 68, Issue 2, Page(s) 247–256

Abstract: The oncofoetal antigen 5T4 is a promising T cell target in the context of colorectal cancer, as demonstrated by a recent clinical study where 5T4-specific T cell responses, induced by vaccination or cyclophosphamide, were associated with a significantly ... ...

Abstract	The oncofoetal antigen 5T4 is a promising T cell target in the context of colorectal cancer, as demonstrated by a recent clinical study where 5T4-specific T cell responses, induced by vaccination or cyclophosphamide, were associated with a significantly prolonged survival of patients with metastatic disease. Whilst Th1-type (IFN-γ
MeSH term(s)	Antigens, Neoplasm/immunology ; Antigens, Neoplasm/metabolism ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; Cancer Vaccines/immunology ; Cells, Cultured ; Colorectal Neoplasms/immunology ; Colorectal Neoplasms/metabolism ; Drug Design ; Epitopes/immunology ; Epitopes/metabolism ; HLA-DR Antigens/immunology ; Humans ; Interferon-gamma/immunology ; Interferon-gamma/metabolism ; Peptides/immunology ; Peptides/metabolism ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; Th1 Cells/immunology ; Th1 Cells/metabolism
Chemical Substances	Antigens, Neoplasm ; Cancer Vaccines ; Epitopes ; HLA-DR Antigens ; Peptides ; oncofetal antigens ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2018-11-07
Publishing country	Germany
Document type	Journal Article
ZDB-ID	195342-4
ISSN	1432-0851 ; 0340-7004
ISSN (online)	1432-0851
ISSN	0340-7004
DOI	10.1007/s00262-018-2266-1
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Article ; Online: Assessing the prognostic value of preoperative carcinoembryonic antigen-specific T-cell responses in colorectal cancer.

Scurr, Martin J / Brown, Clare M / Costa Bento, Diana F / Betts, Gareth J / Rees, Brian I / Hills, Robert K / Gallimore, Awen / Godkin, Andrew

Journal of the National Cancer Institute

2015 Volume 107, Issue 4

Abstract: Current dogma suggests that tumor-reactive IFN-γ-producing (TH1-type) T-cells are beneficial to patient outcome; however, the clinical consequence of these responses with respect to long-term prognosis in colorectal cancer (CRC) is not understood. Here, ... ...

Abstract	Current dogma suggests that tumor-reactive IFN-γ-producing (TH1-type) T-cells are beneficial to patient outcome; however, the clinical consequence of these responses with respect to long-term prognosis in colorectal cancer (CRC) is not understood. Here, we compared the utility of preoperative, peripheral blood-derived IFN-γ(+) T-cell responses specific to carcinoembryonic antigen (CEA), 5T4, or control antigens (n = 64) with tumor staging and clinical details (n = 87) in predicting five-year outcome of CRC patients who underwent resection with curative intent. Although disease recurrence was more likely in patients with stage III tumors, the presence of preoperative, CEA-specific IFN-γ-producing T-cells identified patients at a statistically significantly greater risk of tumor recurrence following surgical resection, irrespective of tumor stage (odds ratio = 5.00, 95% confidence interval = 1.96 to 12.77, two-sided P <.001). Responses to other antigens, including 5T4, did not reflect outcome. Whilst these results initially appear surprising, they could improve prognostication and help redirect adjuvant treatments.
MeSH term(s)	Adult ; Aged ; Biomarkers, Tumor/blood ; Carcinoembryonic Antigen/immunology ; Colorectal Neoplasms/immunology ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/surgery ; Female ; Humans ; Interferon-gamma/immunology ; Lymphatic Metastasis ; Male ; Membrane Glycoproteins/immunology ; Middle Aged ; Neoplasm Recurrence, Local/immunology ; Neoplasm Staging ; Odds Ratio ; Predictive Value of Tests ; Prognosis ; Risk Assessment ; Risk Factors ; T-Lymphocytes/immunology
Chemical Substances	Biomarkers, Tumor ; Carcinoembryonic Antigen ; Membrane Glycoproteins ; trophoblastic glycoprotein 5T4, human ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2015-02-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2992-0
ISSN	1460-2105 ; 0027-8874 ; 0198-0157
ISSN (online)	1460-2105
ISSN	0027-8874 ; 0198-0157
DOI	10.1093/jnci/djv001
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Article ; Online: Response to COVID-19 booster vaccinations in seronegative people with MS.

medRxiv

Abstract: Importance: Uncertainties remain about the benefit of a 3rd COVID-19 vaccine for people with attenuated response to earlier vaccines. This is of particular relevance for people with multiple sclerosis (pwMS) treated with anti-CD20 therapies and ... ...

Abstract	Importance: Uncertainties remain about the benefit of a 3rd COVID-19 vaccine for people with attenuated response to earlier vaccines. This is of particular relevance for people with multiple sclerosis (pwMS) treated with anti-CD20 therapies and fingolimod, who have substantially reduced antibody responses to initial vaccine course. Objective: To report humoral and T-cell responses following COVID-19 vaccine 3 in pwMS who were seronegative after COVID-19 vaccines 1&2. Design, setting and participants: PwMS taking part in a seroprevalence study without a detectable IgG response following COVID-19 vaccines 1&2 were invited to participate. Participants provided a dried blood spot +/- venous blood sample 2-12 weeks following COVID-19 vaccine 3. Data on demographics, MS treatment, and COVID-19 infection/vaccine dates were derived from the medical notes. Methods: Humoral and T cell responses to SARS-CoV-2 spike protein and nucleocapsid antigen were measured. The relationship between evidence of prior COVID-19 infection and immune response to COVID-19 vaccine 3 was evaluated using Fishers exact test. Results: Of 81 participants, 79 provided a dried blood spot sample, of whom 38 also provided a whole blood sample; 2 provided only whole blood. Anti-SARS-CoV-2-spike IgG seroconversion post-COVID-19 vaccine 3 occurred in 26/79 (33%) participants; 26/40 (65%) had positive T-cell responses. Overall, 31/40 (78%) demonstrated either humoral or cellular immune response post-COVID-19 vaccine 3. There no association between laboratory evidence of prior COVID-19 infection and anti-spike seroconversion following COVID-19 vaccine 3. Conclusions: Approximately one third of pwMS who were seronegative after initial COVID-19 vaccination seroconverted after booster (third) vaccination, supporting the use of boosters in this group. Almost 8 out of 10 had a measurable immune response following 3rd COVID-19 vaccine.
Keywords	covid19
Language	English
Publishing date	2022-03-13
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2022.03.12.22272083
Database	COVID19

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Article ; Online: Cancer Antigen Discovery Is Enabled by RNA Sequencing of Highly Purified Malignant and Nonmalignant Cells.

Scurr, Martin J / Greenshields-Watson, Alex / Campbell, Emma / Somerville, Michelle S / Chen, Yuan / Hulin-Curtis, Sarah L / Burnell, Stephanie E A / Davies, James A / Davies, Michael M / Hargest, Rachel / Phillips, Simon / Christian, Adam D / Ashelford, Kevin E / Andrews, Robert / Parker, Alan L / Stanton, Richard J / Gallimore, Awen / Godkin, Andrew

Clinical cancer research : an official journal of the American Association for Cancer Research

2020 Volume 26, Issue 13, Page(s) 3360–3370

Abstract: Purpose: Broadly expressed, highly differentiated tumor-associated antigens (TAA) can elicit antitumor immunity. However, vaccines targeting TAAs have demonstrated disappointing clinical results, reflecting poor antigen selection and/or ... ...

Abstract	Purpose: Broadly expressed, highly differentiated tumor-associated antigens (TAA) can elicit antitumor immunity. However, vaccines targeting TAAs have demonstrated disappointing clinical results, reflecting poor antigen selection and/or immunosuppressive mechanisms. Experimental design: Here, a panel of widely expressed, novel colorectal TAAs were identified by performing RNA sequencing of highly purified colorectal tumor cells in comparison with patient-matched colonic epithelial cells; tumor cell purification was essential to reveal these genes. Candidate TAA protein expression was confirmed by IHC, and preexisting T-cell immunogenicity toward these antigens tested. Results: The most promising candidate for further development is DNAJB7 [DnaJ heat shock protein family (Hsp40) member B7], identified here as a novel cancer-testis antigen. It is expressed in many tumors and is strongly immunogenic in patients with cancers originating from a variety of sites. DNAJB7-specific T cells were capable of killing colorectal tumor lines Conclusions: This study highlights how prior methods that sequence whole tumor fractions (i.e., inclusive of alive/dead stromal cells) for antigen identification may have limitations. Through tumor cell purification and sequencing, novel candidate TAAs have been identified for future immunotherapeutic targeting.
MeSH term(s)	Antigens, Neoplasm/genetics ; Antigens, Neoplasm/immunology ; Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Cytotoxicity, Immunologic ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic ; High-Throughput Nucleotide Sequencing ; Humans ; Immunophenotyping ; Leukocytes, Mononuclear/immunology ; Leukocytes, Mononuclear/metabolism ; Neoplasms/genetics ; Neoplasms/immunology ; Sequence Analysis, RNA ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Tumor Cells, Cultured
Chemical Substances	Antigens, Neoplasm ; Antineoplastic Agents
Language	English
Publishing date	2020-03-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-19-3087
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