7 results on '"Robyn L. Shea"'
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2. Omicron neutralising antibodies after third COVID-19 vaccine dose in patients with cancer
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Annika Fendler, Scott T C Shepherd, Lewis Au, Mary Wu, Ruth Harvey, Andreas M Schmitt, Zayd Tippu, Benjamin Shum, Sheima Farag, Aljosja Rogiers, Eleanor Carlyle, Kim Edmonds, Lyra Del Rosario, Karla Lingard, Mary Mangwende, Lucy Holt, Hamid Ahmod, Justine Korteweg, Tara Foley, Taja Barber, Andrea Emslie-Henry, Niamh Caulfield-Lynch, Fiona Byrne, Daqi Deng, Svend Kjaer, Ok-Ryul Song, Christophe Queval, Caitlin Kavanagh, Emma C Wall, Edward J Carr, Simon Caidan, Mike Gavrielides, James I MacRae, Gavin Kelly, Kema Peat, Denise Kelly, Aida Murra, Kayleigh Kelly, Molly O'Flaherty, Robyn L Shea, Gail Gardner, Darren Murray, Nadia Yousaf, Shaman Jhanji, Kate Tatham, David Cunningham, Nicholas Van As, Kate Young, Andrew J S Furness, Lisa Pickering, Rupert Beale, Charles Swanton, Sonia Gandhi, Steve Gamblin, David L V Bauer, George Kassiotis, Michael Howell, Emma Nicholson, Susanna Walker, James Larkin, and Samra Turajlic
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COVID-19 Vaccines ,Letter ,SARS-CoV-2 ,Neoplasms ,Correspondence ,COVID-19 ,Humans ,General Medicine ,Antibodies, Viral ,Antibodies, Neutralizing - Published
- 2022
3. Functional immune responses against SARS-CoV-2 variants of concern after fourth COVID-19 vaccine dose or infection in patients with blood cancer
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Annika Fendler, Scott T.C. Shepherd, Lewis Au, Mary Wu, Ruth Harvey, Katalin A. Wilkinson, Andreas M. Schmitt, Zayd Tippu, Benjamin Shum, Sheima Farag, Aljosja Rogiers, Eleanor Carlyle, Kim Edmonds, Lyra Del Rosario, Karla Lingard, Mary Mangwende, Lucy Holt, Hamid Ahmod, Justine Korteweg, Tara Foley, Taja Barber, Andrea Emslie-Henry, Niamh Caulfield-Lynch, Fiona Byrne, Daqi Deng, Svend Kjaer, Ok-Ryul Song, Christophe J. Queval, Caitlin Kavanagh, Emma C. Wall, Edward J. Carr, Simon Caidan, Mike Gavrielides, James I. MacRae, Gavin Kelly, Kema Peat, Denise Kelly, Aida Murra, Kayleigh Kelly, Molly O’Flaherty, Robyn L. Shea, Gail Gardner, Darren Murray, Sanjay Popat, Nadia Yousaf, Shaman Jhanji, Kate Tatham, David Cunningham, Nicholas Van As, Kate Young, Andrew J.S. Furness, Lisa Pickering, Rupert Beale, Charles Swanton, Sonia Gandhi, Steve Gamblin, David L.V. Bauer, George Kassiotis, Michael Howell, Emma Nicholson, Susanna Walker, Robert J. Wilkinson, James Larkin, and Samra Turajlic
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Model organisms ,COVID-19 Vaccines ,Immunology ,T cells ,Infectious Disease ,variants of concern ,Antibodies, Viral ,Biochemistry & Proteomics ,General Biochemistry, Genetics and Molecular Biology ,Signalling & Oncogenes ,Ecology,Evolution & Ethology ,Neoplasms ,Humans ,neutralizing antibodies ,BNT162 Vaccine ,Computational & Systems Biology ,Chemical Biology & High Throughput ,Human Biology & Physiology ,SARS-CoV-2 ,blood cancer ,FOS: Clinical medicine ,Stem Cells ,Clinical Studies as Topic ,Genome Integrity & Repair ,Immunity ,Neurosciences ,COVID-19 ,Cell Biology ,Tumour Biology ,Antibodies, Neutralizing ,Metabolism ,Cell Cycle & Chromosomes ,Genetics & Genomics ,Developmental Biology ,Structural Biology & Biophysics - Abstract
Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886), we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralizing antibody titers (NAbTs) using a live virus microneutralization assay against wild-type (WT), Delta, and Omicron BA.1 and BA.2 and T cell responses against WT and Omicron BA.1 using an activation-induced marker (AIM) assay. The proportion of patients with detectable NAb titers and T cell responses after the fourth vaccine dose increased compared with that after the third vaccine dose. Patients who received B cell-depleting therapies within the 12 months before vaccination have the greatest risk of not having detectable NAbT. In addition, we report immune responses in 57 patients with breakthrough infections after vaccination.
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- 2022
- Full Text
- View/download PDF
4. Functional antibody and T cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study
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Lisa Pickering, Richard Stone, Ian Chau, James I. MacRae, Karla Lingard, Susana Banerjee, Barry Ward, Jessica Bazin, William Gordon, Naureen Starling, Katalin A. Wilkinson, Mary O'Brien, Anna Robinson, Joanne Droney, Sacheen Kumar, Emma Nicholson, Martin Pule, Isla Leslie, Andreas M. Schmitt, Ambrosius P. Snijders, Karolina Rzeniewicz, Emma Nye, Benjamin Shum, Mary Mangwende, Scott Shepherd, Nalinie Joharatnam-Hogan, Robyn L. Shea, Michael Howell, Anthony J. Swerdlow, Shaman Jhanji, Simon Caidan, Eleanor Carlyle, Laura Amanda Boos, Annika Fendler, Kevin W. Ng, Kate Tatham, Leila Mekkaoui, Tim Slattery, Margaret Crawford, Firza Gronthoud, Philip Hobson, Camila Gomes, Robert J. Wilkinson, Jerome Nicod, Charles Swanton, Mike Gavrielides, Kim Edmonds, Robin L. Jones, Fiona Byrne, Laura Cubitt, Alison Reid, Lucy Holt, Ana Agua-Doce, Ruth Harvey, Sarah Sarker, Spyridon Gennatas, Camille L. Gerard, Andrew Furness, Hamid Ahmod, Liam Welsh, Nicholas van As, Olivia Curtis, Nadia Yousaf, Mary Wu, Nicholas C. Turner, Christina Messiou, David Cunningham, Zayd Tippu, Georgina H. Cornish, Sonia Gandhi, Helen R. Flynn, Harshil Patel, Yasir Khan, James Larkin, Lewis Au, George Kassiotis, Samra Turajlic, Maddalena Cerrone, Clemency Stephenson, Steve Gamblin, Kate Young, Wenyi Xie, Shreerang Bhide, Robert L. Goldstone, Alicia Okines, Kevin J. Harrington, Lyra Del Rosario, and Wellcome Trust
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Cancer Research ,IMPACT ,Antibody Response ,Alpha (ethology) ,CORONAVIRUS DISEASE 2019 ,Disease ,Adaptive Immunity ,Article ,Immune system ,SEROCONVERSION ,Medicine ,Neutralizing antibody ,Cancer ,Science & Technology ,biology ,SARS-CoV-2 ,business.industry ,MORTALITY ,COVID-19 ,medicine.disease ,Titer ,SEVERITY ,Oncology ,Immunology ,Cohort ,biology.protein ,Prospective Study ,Antibody ,business ,Neutralising Antibodies ,Vaccine ,Life Sciences & Biomedicine ,T-cell Response - Abstract
Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study, integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2 positive, 94 were symptomatic and 2 died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies and 82% had neutralizing antibodies against wild type SARS-CoV-2, whereas neutralizing antibody titers against the Alpha, Beta and Delta variants were substantially reduced. S1-reactive antibody levels decreased in 13% of patients, whereas neutralizing antibody titers remained stable for up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment specific, but presented compensatory cellular responses, further supported by clinical recovery in all but one patient. Overall, these findings advance the understanding of the nature and duration of the immune response to SARS-CoV-2 in patients with cancer.
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- 2022
- Full Text
- View/download PDF
5. Immune responses following third COVID-19 vaccination are reduced in patients with hematologic malignancies compared to patients with solid cancer
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Annika Fendler, Scott T.C. Shepherd, Lewis Au, Katalin A. Wilkinson, Mary Wu, Andreas M. Schmitt, Zayd Tippu, Sheima Farag, Aljosja Rogiers, Ruth Harvey, Eleanor Carlyle, Kim Edmonds, Lyra Del Rosario, Karla Lingard, Mary Mangwende, Lucy Holt, Hamid Ahmod, Justine Korteweg, Tara Foley, Taja Barber, Andrea Emslie-Henry, Niamh Caulfield-Lynch, Fiona Byrne, Benjamin Shum, Camille L. Gerard, Daqi Deng, Svend Kjaer, Ok-Ryul Song, Christophe Queval, Caitlin Kavanagh, Emma C. Wall, Edward J. Carr, Sina Namjou, Simon Caidan, Mike Gavrielidis, James McRae, Gavin Kelly, Kema Peat, Denise Kelly, Aida Murra, Kayleigh Kelly, Molly O'Flaherty, Robyn L. Shea, Gail Gardner, Darren Murray, Nadia Yousaf, Shaman Jhanji, Nicholas Van As, Kate Young, Andre J.S. Furness, Lisa Pickering, Rupert Beale, Charles Swanton, Sonia Ghandi, Steve Gamblin, David L.V. Bauer, George Kassiotis, Michael Howell, Emma Nicholson, Robert J. Wilkinson, James Larkin, and Samra Turajlic
- Abstract
Not all patients with cancer, in particular those with hematogic malignancies, develop functional immunity against SARS-CoV-2 variants of concern (VOC) following COVID-19 vaccines. Durability of vaccine-induced immunity after two doses and the impact of a third dose were evaluated in CAPTURE (NCT03226886), a longitudinal prospective cohort study of vaccine responses in patients with cancer. In evaluating 316 patients, at a median of 111 days following two doses of either BNT16b2 or ChadOX, we observed a time-dependant decline in neutralising antibody titres (NAbT) in a proportion of patients, where NAbTs became undetectable against Delta and Beta in 17% and 15% of patients, respectively. Vaccine-induced T cell responses declined in 44% of patients. Patients with breakthrough infections following two vaccines doses were characterised by absent/low NAbT to Delta prior to infection. Administration of the third vaccine dose boosted NAb responses against VOC in the majority of patients with cancer, especially those with solid cancer. In patients with hematologic malignancies who had undetectable NAbT against Delta after two vaccine doses, 54% did not develop NAb against both Beta and Delta following the third dose. Third vaccine dose boosted T cell responses were boosted in patients with both solid and hematologic malignancies. These results provide critical information on vaccine responses in patients with cancer, especially against VOCs and support widespread access to a third COVID-19 vaccination in this patient group.
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- 2021
6. Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: The CAPTURE study
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Lisa Pickering, Nalinie Joharatnam-Hogan, Fiona Kinnaird, Andrew Furness, Mary Wu, Daqi Deng, Sina Namjou, Sarah Sarker, Aljosja Rogiers, Aida Murra, Justine Korteweg, Nicholas van As, Nicholas C. Turner, Anna Robinson, Joanne Droney, Kema Peat, Shaman Jhanji, Mike Gavrielides, Isla Leslie, Lauren Dowdie, Tara Foley, Christina Messiou, Natalie Ash, Taja Barber, Andrea Emslie-Henry, Simon Caidan, Karolina Rzeniewicz, Katalin A. Wilkinson, Ruth Harvey, Annika Fendler, Kate Tatham, Andreas M. Schmitt, Sunil Iyengar, Shreerang Bhide, Kayleigh Kelly, David L.V. Bauer, Benjamin Shum, Kim Edmonds, Gail Gardner, Scott Shepherd, Mark Ethell, Laura Amanda Boos, Liam Welsh, Robert J. Wilkinson, Lucy Holt, Alicia Okines, William Gordon, James I. MacRae, Maddalena Cerrone, Kevin J. Harrington, Mary Mangwende, Hamid Ahmod, Olivia Curtis, Emma Nicholson, Darren Murray, Susana Banerjee, Firza Gronthoud, Bhavna Oza, Naureen Starling, Wenyi Xie, Alison Reid, Karla Lingard, Ana Agua-Doce, Charles Swanton, Sacheen Kumar, Lewis Au, Michael Howell, James Larkin, Camille L. Gerard, Emma C Wall, Jessica Bazin, Ian Chau, Robin L. Jones, Fiona Byrne, Robyn L. Shea, Denise Kelly, Nadia Yousaf, Steve Gamblin, Kate Young, Sonia Gandhi, Susanna Walker, Eleanor Carlyle, Javier Pascual, David Cunningham, Samra Turajlic, Clemency Stephenson, Zayd Tippu, Gavin Kelly, Mary O'Brien, Sheima Farag, Molly O’Flaherty, George Kassiotis, Wanyuan Cui, Justin Mencel, Lyra Del Rosario, Simon Rodney, and Wellcome Trust
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Male ,Cancer Research ,T-Lymphocytes ,Antibody Response ,Adaptive Immunity ,IMMUNOGENICITY ,Antibodies, Viral ,COVID-19 VACCINATION ,Immunogenicity, Vaccine ,Neoplasms ,Longitudinal Studies ,Prospective Studies ,Neutralizing antibody ,Prospective cohort study ,Cancer ,Aged, 80 and over ,Immunity, Cellular ,biology ,Vaccination ,Middle Aged ,Acquired immune system ,Kidney Neoplasms ,Oncology ,Female ,Antibody ,Life Sciences & Biomedicine ,Neutralising Antibodies ,T-cell Response ,Adult ,COVID-19 Vaccines ,Article ,MALIGNANCIES ,Crick COVID19 consortium ,Immunity ,VACCINES ,ChAdOx1 nCoV-19 ,medicine ,Humans ,Seroconversion ,Carcinoma, Renal Cell ,Pandemics ,BNT162 Vaccine ,Aged ,Science & Technology ,business.industry ,SARS-CoV-2 ,MORTALITY ,COVID-19 ,medicine.disease ,Antibodies, Neutralizing ,DEMOGRAPHICS ,Immunology ,biology.protein ,Prospective Study ,business ,Vaccine - Abstract
Coronavirus disease 2019 (COVID-19) antiviral response in a pan-tumor immune monitoring (CAPTURE) (NCT03226886) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable titers of neutralizing antibodies (NAbT) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) versus wild-type (WT) SARS-CoV-2. Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT than those with solid cancers against both SARS-CoV-2 WT and VOC. By comparison with individuals without cancer, patients with hematological, but not solid, malignancies had reduced neutralizing antibody (NAb) responses. Seroconversion showed poor concordance with NAbT against VOC. Previous SARS-CoV-2 infection boosted the NAb response including against VOC, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T cell responses were detected in 80% of patients and were comparable between vaccines or cancer types. Our results have implications for the management of patients with cancer during the ongoing COVID-19 pandemic.
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- 2021
7. N-(3-Cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amides as potent, selective, inhibitors of JNK2 and JNK3
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Margarete Neu, Donald O. Somers, Gladstone Thompson, Richard Martyn Angell, Kendra E. Hightower, Jeffery L. Smith, Maria Cichy-Knight, Tsu Tshen Chuang, Ruolan Wang, Murray J. B. Brown, Sonia Thomas, Allison K. Dunn, Robyn L. Shea, Susanna Malkakorpi, James R. Musgrave, Francis Louis Atkinson, John A. Christopher, and Paul Rowland
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Nitrile ,Stereochemistry ,medicine.drug_class ,Clinical Biochemistry ,Substituent ,Pharmaceutical Science ,Carboxamide ,Crystallography, X-Ray ,Biochemistry ,Chemical synthesis ,chemistry.chemical_compound ,Structure-Activity Relationship ,Mitogen-Activated Protein Kinase 10 ,Amide ,Drug Discovery ,medicine ,Benzene Derivatives ,Structure–activity relationship ,Humans ,Mitogen-Activated Protein Kinase 9 ,Binding site ,Molecular Biology ,Binding Sites ,Chemistry ,Kinase ,Organic Chemistry ,Amides ,Molecular Medicine - Abstract
The identification and exploration of a novel, potent and selective series of N-(3-cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amide inhibitors of JNK2 and JNK3 kinases is described. Compounds 5a and 11a were identified as potent inhibitors of JNK3 (pIC50 6.7 and 6.6, respectively), with essentially equal potency against JNK2 (pIC50 6.5). Selectivity within the mitogen-activated protein kinase (MAPK) family, against JNK1, p38alpha and ERK2, was observed for the series. X-ray crystallography of 5e and 8a in JNK3 revealed a unique binding mode, with the 3-cyano substituent forming an H-bond acceptor interaction with the hinge region of the ATP-binding site.
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- 2006
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