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1. The development of novel therapeutic vaccines for chronic hepatitis B infection

Author

Cargill, Tamsin, Klenerman, Paul, and Barnes, Eleanor

Subjects
Immunology, Hepatology
Abstract

Chronic infection with Hepatitis B virus (HBV) remains a significant health problem, infecting millions of people worldwide. Cirrhosis and hepatocellular carcinoma, the sequalae of longstanding HBV infection, have a high mortality. Current therapy controls HBV replication but does not eradicate the virus, and therefore most people require life-long treatment. A robust adaptive immune response is required to control acute HBV but is dysfunctional in individuals that go onto develop chronic infection. The immune response is an attractive target for novel HBV therapies, which aim to induce functional cure of HBV in finite treatment courses by restoring HBV specific immunity. Therapeutic vaccination, which describes the process of delivering non-infective HBV antigen into the body in order to induce or boost cellular immune responses to HBV, is one strategy under investigation for chronic HBV treatment. In this thesis I evaluate the novel vaccines ChAdOx1-HBV and MVA-HBV as candidates for HBV therapeutic vaccination. I investigate their immunogenicity in heterologous prime-boost strategies in healthy mice, describing in detail the fine specificity, functionality and phenotype of vaccine induced T cell responses in the blood and the liver. I also describe the safety and immunogenicity ChAdOx1-HBV in a phase-1 open label clinical trial in healthy volunteers and patients with chronic HBV infection. This work is important to inform the development of therapeutic strategies using ChAdOx1-HBV and MVA-HBV in patients with chronic HBV going forward.

Published
2021

3. Outcomes following SARS-CoV-2 infection in patients with chronic liver disease: An international registry study

Author

Marjot, Thomas, Moon, Andrew M., Cook, Jonathan A., Abd-Elsalam, Sherief, Aloman, Costica, Armstrong, Matthew J., Pose, Elisa, Brenner, Erica J., Cargill, Tamsin, Catana, Maria-Andreea, Dhanasekaran, Renumathy, Eshraghian, Ahad, García-Juárez, Ignacio, Gill, Upkar S., Jones, Patricia D., Kennedy, James, Marshall, Aileen, Matthews, Charmaine, Mells, George, Mercer, Carolyn, Perumalswami, Ponni V., Avitabile, Emma, Qi, Xialong, Su, Feng, Ufere, Nneka N., Wong, Yu Jun, Zheng, Ming-Hua, Barnes, Eleanor, Barritt, Alfred S., IV, and Webb, Gwilym J.

Published
2021
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4. Outcomes following SARS-CoV-2 infection in liver transplant recipients: an international registry study

Author

Webb, Gwilym J, Marjot, Thomas, Cook, Jonathan A, Aloman, Costica, Armstrong, Matthew J, Brenner, Erica J, Catana, Maria-Andreea, Cargill, Tamsin, Dhanasekaran, Renumathy, García-Juárez, Ignacio, Hagström, Hannes, Kennedy, James M, Marshall, Aileen, Masson, Steven, Mercer, Carolyn J, Perumalswami, Ponni V, Ruiz, Isaac, Thaker, Sarang, Ufere, Nneka N, Barnes, Eleanor, Barritt, Alfred S, IV, and Moon, Andrew M

Published
2020
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5. Novel genetically-modified chimpanzee adenovirus and MVA-vectored respiratory syncytial virus vaccine safely boosts humoral and cellular immunity in healthy older adults

Author

Green, Christopher A., Sande, Charles J., Scarselli, Elisa, Capone, Stefania, Vitelli, Alessandra, Nicosia, Alfredo, Silva-Reyes, Laura, Thompson, Amber J., de Lara, Catherine M., Taylor, Kathryn S., Haworth, Kathryn, Hutchings, Claire L., Cargill, Tamsin, Angus, Brian, Klenerman, Paul, and Pollard, Andrew J.

Published
2019
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8. Effect of Prior ChAdOx1 COVID-19 Immunisation on T-Cell Responses to ChAdOx1-HBV †.

Author

Davis, Charlotte, Singh, Dave, Anderson, Katie, Vardeu, Antonella, Kopycinski, Jakub, Bridges-Webb, Alice, Trickett, Alice, O'Brien, Susanne, Downs, Matthew, Kaur, Randip, Kolenovska, Radka, Bussey, Louise, Rutkowski, Kathryn, Sebastian, Sarah, Cargill, Tamsin, Barnes, Eleanor, Evans, Thomas G., and Cicconi, Paola

Subjects
T cells, IMMUNIZATION, GENETIC vectors, INTRAMUSCULAR injections, ANTIBODY titer
Abstract

There are varying data concerning the effect of prior anti-vector immunity on the T-cell response induced by immunisation with an identical vectored vaccine containing a heterologous antigen insert. To determine whether prior exposure to ChAdOx1-SARS-CoV2 immunisation (Vaxzevria®) impacts magnitudes of antigen-specific T-cell responses elicited by subsequent administration of the same viral vector (encoding HBV antigens, ChAdOx1-HBV), healthy volunteers that had received Vaxzevria® (n = 15) or the Pfizer or Moderna mRNA COVID-19 vaccine (n = 11) between 10 and 18 weeks prior were recruited to receive a single intramuscular injection of ChAdOx1-HBV. Anti-ChAdOx1-neutralising antibody titers were determined, and vector or insert-specific T-cell responses were measured by a gamma-interferon ELISpot and intracellular cytokine staining (ICS) assay using multiparameter flow cytometry. Participants were followed for three months after the ChAdOx1-HBV injection, which was well-tolerated, and no dropouts occurred. The baseline ChAdOx1 neutralisation titers were higher in the Vaxzevria® cohort (median of 848) than in the mRNA cohort (median of 25). T-cell responses to HBV antigens, measured by ELISpot, were higher on day 28 in the mRNA group (p = 0.013) but were similar between groups on day 84 (p = 0.441). By ICS, these differences persisted at the last time point. There was no clear correlation between the baseline responses to the adenoviral hexon and the subsequent ELISpot responses. As vaccination within 3 months using the same viral vector backbone affected the insert-specific T-cell responses, a greater interval after prior adenoviral immunisation using heterologous antigens may be warranted in settings in which these cells play critical roles. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Regional variation in characteristics of patients with decompensated cirrhosis admitted to hospitals in the UK

Author

Tavabie, Oliver D, primary, Abeysekera, Kushala WM, additional, Brennan, Paul N, additional, Marjot, Thomas, additional, Kronsten, Victoria T, additional, Li, Wenhao, additional, Nayagam, Jeremy S, additional, Dhaliwal, Amritpal, additional, Hardy, Tim, additional, Maurice, James B, additional, Zakeri, Nekisa, additional, Abbas, Nadir, additional, Abbasi, Abdullah, additional, Abbott, Jane, additional, Abdul, Rahman, additional, Abdulaziz, Mohamed, additional, Abduljabbar, Duaa, additional, Adamson, Robbie, additional, Adebayo, Danielle, additional, Adhikarla, Aditya Kumar, additional, Adler, Maciej, additional, Afifi, Mostafa, additional, Ahmad, Salman, additional, Ahmed, Shayan, additional, Aithal, Guruprasad, additional, Akram, Ali, additional, Al Radhi, Balqees, additional, Al-Talib, Ismaeel, additional, Alele, Jolomi, additional, Ali, Alaa Mohammed, additional, Almusai, Safa, additional, Appleby, Victoria, additional, Asmat, Huma, additional, Astbury, Sarah, additional, Atkinson, Ali, additional, Badrulhisham, Fakhirah, additional, Balachandrakumar, Vinay K, additional, Ball, Alexandra, additional, Banfa, Moses, additional, Barn, Jeevan, additional, Begum, Shahnaz, additional, Belfield, Katherine, additional, Bendall, Oliver, additional, Bennett, Kris, additional, Bernal, William, additional, Bhandari, Rajan, additional, Bhatti, Prashan, additional, Bradley, Meg, additional, Brown, Edward, additional, Bryce, Kathleen, additional, Buchanan, Ryan, additional, Burke, Laura, additional, Campbell, Roisin, additional, Cargill, Tamsin, additional, Carroll, Geraldine, additional, Cartledge, James, additional, Chatterjee, Devnandan, additional, Chaundry, Rayan, additional, Choudhry, Zeshan, additional, Clare, Kathleen, additional, Cobbold, Jeremy, additional, Coburn, Robert, additional, Cook, Charlotte, additional, Corvan, Fintan, additional, Cox, Rebecca, additional, Craig, Darren, additional, Creamer, John, additional, Curran, Christopher, additional, De Silva, Shanika, additional, Dean, Laurence, additional, Dillon, Jayne, additional, Dillon, John, additional, Dunn, Rebecca, additional, Eckersley, Robert, additional, Eike, Gidveig, additional, Elagib, Amul, additional, Elkholi, Ayman, additional, Elshaarawy, Omar, additional, Faloon, Sarah, additional, Fan, Francis, additional, Fazili, Mohammad, additional, Fernandes, Denzil, additional, Fox, James, additional, Foxton, Matthew, additional, Gaba, Waqas, additional, Gaikwad, Girish, additional, Gairola, Abishek, additional, Galanakis, Vasileios, additional, Gallaher, Charles, additional, Gautam, Nisham, additional, Germain, Lewis, additional, Giles, Ben, additional, Gill, Ceri, additional, Glover, Ben, additional, Glover, John, additional, Gomez, David, additional, Gomez, Michael, additional, Gordon, Victoria, additional, Gormley, Sarah, additional, Goulder, John, additional, Goyal, Simran, additional, Greenham, Olivia, additional, Guthrie, Sarah, additional, Hackett, Richard, additional, Haddadin, Yazan, additional, Hadjinicolaou, Andreas, additional, Hall, Jonathan, additional, Hamza, Mohammed, additional, Haque, Tasnuma, additional, Harris, Rebecca, additional, Hart, Catherine, additional, Hasan, Sundas, additional, Hasnain Nadir, Syed Mujtaba, additional, Hassall, James, additional, Hawker-Bond, George, additional, Hawkyard, Jake, additional, Healey, Scott, additional, Hogan, Brian, additional, Hornby, Catherine, additional, Humayun, MD, additional, Hutchison, John, additional, Iftikhar, Zahra, additional, Ismail, Asem, additional, James, Joel, additional, Jones, Rebecca, additional, Jopson, Laura, additional, Juthani, Dipal, additional, Kaina, Philippa, additional, Karim, Aadil, additional, Karim, Syed Misbah, additional, Kashyap, Vaishnavi, additional, Kassab, Mohamed, additional, Katarey, Dev, additional, Kenny, Lee, additional, Kerry, Georgina, additional, Khan, Adnan, additional, Khan, Ayesha, additional, Khan, Azab, additional, Khan, Muhammad Taha, additional, Khan, Tahir, additional, Khatib, Aseil, additional, Khattak, Mohammad Fawad, additional, King, Ji Jade, additional, Kooner, Emily, additional, Korani, Mohammed, additional, Kotha, Sreelakshmi, additional, Lam, Wai Liam, additional, Lateef, Mohammed, additional, Leighton, Jess, additional, Leith, Damien, additional, Liaros, Angela, additional, Liu Yin, James, additional, Lourenco, Floyd, additional, Lyles, Annabel, additional, Macken, Lucia, additional, Magee, Ciaran, additional, Maggs, Daniel, additional, Mahalingam, Aarani, additional, Mahenthiran, Midusa, additional, Mahmood, Rizwan, additional, Mandour, Mandour Omer, additional, Manocha, Namita, additional, Mansour, Dina, additional, Marks, Daniella, additional, Martin, Ciara, additional, Martin, Harry, additional, Martin, Iana, additional, Martin, Katherine, additional, Maruthan, Sachan, additional, Masin, Rhys, additional, Mason, Denise, additional, Matthews, Charmaine, additional, Mavrou, Athina, additional, Maxan, Ema, additional, Maxfield, Dominic, additional, McAvoy, Emma, additional, McCaughan, Hannah, additional, McColl, Kirsty, additional, McCorry, Roger, additional, McDonald, Stewart, additional, McDowell, Hannah, additional, McGoran, John, additional, McIlwane, Stewart, additional, McPherson, Stuart, additional, Meakin, Olivia, additional, Mebarek, Leila, additional, Merrill, Hannah, additional, Michail, Stephanie, additional, Modarres, Pedram, additional, Mohamedali, Alaa, additional, Mohammed, Yaser, additional, Mohammed, Zakiuddin, additional, Mohan, Jaiganesh, additional, Monnier, Chloe, additional, Moran, Eilis, additional, Moroni, Francesca, additional, Morrison, Gary, additional, Msaddi, Anas, additional, Mutar, Sarah, additional, Nahed, Ismail, additional, Navaratnam, Janardhan, additional, Neto-Pereira, Luis, additional, Ng, Jennifer, additional, Nwoguh, Chinonso, additional, O'Kane, Rebecca, additional, Omar, Sohail, additional, Ososanya, Abosede, additional, Parambil, Jessiya Veliyankodan, additional, Patel, Jay, additional, Pericleous, Marinos, additional, Pervais, Zeshan, additional, Phoolchund, Anju, additional, Pietrzycki, Julian, additional, Pillay, Lushen, additional, Pohl, Keith, additional, Prabhu, Kiran, additional, Putri, Yesita Rizky F., additional, Qazi, Umang, additional, Rafique, Khizar Khalid, additional, Raghuraman, Arun, additional, Raman, Krithivasan, additional, Ranade, Vaishali, additional, Rastelli, Francesca, additional, Ratcliffe, Elizabeth, additional, Rattehalli, Deepa, additional, Raza, Tufail, additional, Razak, Amir, additional, Read, George, additional, Robins, Anne, additional, Rowe, Ian, additional, Rushbrook, Simon, additional, Salama, Mohamed, additional, Saravan, Ramasamy, additional, Sarkar, Srishti, additional, Saunsbury, Emma, additional, Scott, Jennifer, additional, Serna, Solange, additional, Shahzad, Hassnain, additional, Shamsaldeen, Mohammed, additional, Sharip, Mohammed, additional, Shearer, Jessica, additional, Sheikh, Adam, additional, Sheiybani, Giovanna, additional, Sherwin, Michelle, additional, Sheth, Abhishek, additional, Shintre, Nidhi, additional, Singhal, Saket, additional, Sinha, Rohit, additional, Sinharay, Ricky, additional, Smith, Gloria, additional, Smith, Ria, additional, Snowdon, Victoria, additional, Spicer, Joanne, additional, Spoor, Johannes, additional, Sreenivasan, Shiva, additional, Srinivasa, Amar, additional, Srivastava, Ankur, additional, St. Aimee, Louise, additional, Stagg, Georgia, additional, Stanley, Jatinder, additional, Stevenson, Jason, additional, Stokes, Daniel, additional, Stroud, Robert, additional, Subhani, Mohsan, additional, Suliman, Hiba, additional, Sultana, Marium, additional, Summers, Nikki, additional, Sutherland, Chloe, additional, Swann, Rachael, additional, Sykes, Lynne, additional, Taha, Mostafa, additional, Tan, Kwei Eng, additional, Tariq, Zohaib, additional, Tay, Joshua Jun Ming, additional, Taylor, Alison, additional, Thakor, Amit, additional, Tsang, James, additional, Turner, Lucy, additional, Tyler, Zaccharie, additional, Unitt, Esther, additional, Volcek, Edward, additional, Watson, Iona, additional, Watters, Chris, additional, Wells, Gemma, additional, White, Helen, additional, Widlak, Monika, additional, Williams, Matthew, additional, Wischhusen, Jack, additional, Woodland, Hazel, additional, Wren, Louise, additional, Xyda, Souzana, additional, Yeh, Julian, additional, Young, Alison, additional, and Yuan, Jack Shie Jie, additional

Published
2023
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16. Defining characteristics and outcomes for patients with non-alcoholic fatty liver disease admitted to hospital with decompensated cirrhosis

Author

Tavabie, Oliver D., Abbott, Jane, Abeysekera, Kushala WM., Balachandrakumar, Vinay K., Bennett, Kris, Brennan, Paul, Buchanan, Ryan, Dhaliwal, Amritpal, Galanakis, Vasileios, Hardy, Tim, Harris, Rebecca, Kronsten, Victoria T., Leighton, Jess, Li, Wenhao, Yin, James Liu, Macken, Lucia, Marjot, Thomas, Maurice, James B., McDowell, Hannah, Navaratnam, Janardhan, Pohl, Keith, Nayagam, Jeremy S., Saunsbury, Emma, Scott, Jennifer, Sheth, Abhishek, Sinharay, Ricky, Sheiybani, Giovanna, Subhani, Mohsan, Turner, Lucy, White, Helen, Zakeri, Nekisa, Cook, Charlotte, Abbas, Nadir, Abbasi, Abdullah, Abdul, Rahman, Abdulaziz, Mohamed, Abduljabbar, Duaa, Adamson, Robbie, Adebayo, Danielle, Adhikarla, Aditya Kumar, Adler, Maciej, Ahmad, Salman, Ahmed, Shayan, Afifi, Mostafa, Akram, Ali, Al Radhi, Balqees, Al-Talib, Ismaeel, Alele, Jolomi, Ali, Alaa Mohammed, Almusai, Safa, Appleby, Victoria, Asmat, Huma, Astbury, Sarah, Atkinson, Ali, Badrulhisham, Fakhirah, Ball, Alexandra, Banfa, Moses, Barn, Jeevan, Begum, Shahnaz, Belfield, Katherine, Bendall, Oliver, Bhandari, Rajan, Bhatti, Prashan, Bradley, Meg, Brown, Edward, Bryce, Kathleen, Burke, Laura, Campbell, Roisin, Cargill, Tamsin, Carroll, Geraldine, Cartledge, James, Chatterjee, Devnandan, Chaundry, Rayan, Choudhry, Zeshan, Clare, Kathleen, Cobbold, Jeremy, Coburn, Robert, Corvan, Fintan, Cox, Rebecca, Craig, Darren, Creamer, John, Curran, Christopher, De Silva, Shanika, Dean, Laurence, Dillon, Jayne, Dunn, Rebecca, Eckersley, Robert, Eike, Gidveig, Elagib, Amul, Elkholi, Ayman, Elshaarawy, Omar, Faloon, Sarah, Fan, Francis, Fazili, Mohammad, Fernandes, Denzil, Fox, James, Foxton, Matthew, Gaba, Waqas, Gaikwad, Girish, Gairola, Abishek, Gallaher, Charles, Gautam, Nisham, Germain, Lewis, Giles, Ben, Gill, Ceri, Glover, Ben, Glover, John, Gomez, David, Gomez, Michael, Gordon, Victoria, Gormley, Sarah, Goulder, John, Goyal, Simran, Greenham, Olivia, Guthrie, Sarah, Hackett, Richard, Haddadin, Yazan, Hadjinicolaou, Andreas, Hall, Jonathan, Haque, Tasnuma, Hart, Catherine, Hasnain Nadir, Syed Mujtaba, Hassall, James, Hasan, Sundas, Hawker-Bond, George, Hawkyard, Jake, Healey, Scott, Hornby, Catherine, Hamza, Mohammed, Humayun, M.D., Hutchison, John, Iftikhar, Zahra, Ismail, Asem, James, Joel, Jopson, Laura, Juthani, Dipal, Kaina, Philippa, Karim, Aadil, Karim, Syed Misbah, Kashyap, Vaishnavi, Kassab, Mohamed, Katarey, Dev, Kenny, Lee, Kerry, Georgina, Khan, Adnan, Khan, Ayesha, Khan, Azab, Khan, Muhammad Taha, Khan, Tahir, Khatib, Aseil, Khattak, Mohammad Fawad, King, Ji Jade, Korani, Mohammed, Kotha, Sreelakshmi, Kooner, Emily, Lam, Wai Liam, Lateef, Mohammed, Leith, Damien, Liaros, Angela, Lourenco, Floyd, Lyles, Annabel, Mahenthiran, Midusa, Magee, Ciaran, Maggs, Daniel, Mahalingam, Aarani, Mahmood, Rizwan, Mandour, Mandour Omer, Manocha, Namita, Mansour, Dina, Marks, Daniella, Martin, Ciara, Martin, Harry, Martin, Iana, Martin, Katherine, Maruthan, Sachan, Masin, Rhys, Mason, Denise, Matthews, Charmaine, Mavrou, Athina, Maxan, Ema, Maxfield, Dominic, McAvoy, Emma, McColl, Kirsty, McCaughan, Hannah, McCorry, Roger, McGoran, John, McDonald, Stewart, McIlwane, Stewart, Meakin, Olivia, Mebarek, Leila, Merrill, Hannah, Michail, Stephanie, Modarres, Pedram, Mohamedali, Alaa, Mohammed, Yaser, Mohammed, Zakiuddin, Mohan, Jaiganesh, Monnier, Chloe, Moran, Eilis, Morrison, Gary, Moroni, Francesca, Msaddi, Anas, Mutar, Sarah, Neto-Pereira, Luis, Nahed, Ismail, Ng, Jennifer, Nwoguh, Chinonso, O’Kane, Rebecca, Omar, Sohail, Ososanya, Abosede, Parambil, Jessiya Veliyankodan, Patel, Jay, Pericleous, Marinos, Pervais, Zeshan, Phoolchund, Anju, Pietrzycki, Julian, Pillay, Lushen, Prabhu, Kiran, Putri, Yesita Rizky F., Qazi, Umang, Rafique, Khizar Khalid, Raman, Krithivasan, Ranade, Vaishali, Rastelli, Francesca, Ratcliffe, Elizabeth, Rattehalli, Deepa, Raza, Tufail, Razak, Amir, Raghuraman, Arun, Read, George, Robins, Anne, Rushbrook, Simon, Salama, Mohamed, St. Aimee, Louise, Saravan, Ramasamy, Sarkar, Srishti, Serna, Solange, Shahzad, Hassnain, Shamsaldeen, Mohammed, Sharip, Mohammed, Shearer, Jessica, Sheikh, Adam, Sherwin, Michelle, Shintre, Nidhi, Singhal, Saket, Sinha, Rohit, Smith, Gloria, Smith, Ria, Spicer, Joanne, Spoor, Johannes, Sreenivasan, Shiva, Srinivasa, Amar, Srivastava, Ankur, Stagg, Georgia, Stanley, Jatinder, Stevenson, Jason, Stokes, Daniel, Stroud, Robert, Suliman, Hiba, Sultana, Marium, Summers, Nikki, Sutherland, Chloe, Swann, Rachael, Sykes, Lynne, Taha, Mostafa, Tan, Kwei Eng, Tariq, Zohaib, Ming Tay, Joshua Jun, Taylor, Alison, Thakor, Amit, Tsang, James, Tyler, Zaccharie, Unitt, Esther, Volcek, Edward, Wischhusen, Jack, Watson, Iona, Watters, Chris, Wells, Gemma, Widlak, Monika, Williams, Matthew, Woodland, Hazel, Wren, Louise, Xyda, Souzana, Yeh, Julian, Young, Alison, Jie Yuan, Jack Shie, Aithal, Guruprasad, Bernal, William, Dillon, John, Hogan, Brian, McPherson, Stuart, Jones, Rebecca, Rowe, Ian, and Snowdon, Victoria

Published
2023
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19. The Commissioning and Provision of Advocacy for Problem Drug Users in English DATS: A Cross-Sectional Survey

Author

Cargill, Tamsin, Weaver, Tim D., and Patterson, Sue

Abstract

Aims: This study investigated the commissioning and delivery of advocacy for problem drug users. We aimed to quantify provision, describe the commissioning of advocacy services in Drug Action Teams (DATs) and to identify factors influencing advocacy provision. Methods: A cross-sectional survey of a randomly selected sample of 50 English DATs. The purpose-designed questionnaire comprising a mix of closed and open questions was completed through a telephone interview. Findings: An 86% response rate was achieved. Informants understood "advocacy" as encompassing a range of activities including user involvement and peer support. A range of approaches classified as formal, informal and ad hoc were described. Whilst advocacy was identified as a need in 29 DATs (67%), formal, independent advocacy was commissioned in only four (9%). In eight DATs (19%), there was no advocacy provision of any kind. Conclusions: Advocacy is described by the National Treatment Agency as an essential element of effective drug treatment systems. However, provision in English DATs is inconsistent, poorly integrated with treatment systems and characterized by the absence of strategic planning. Clarification of the concept and purpose of advocacy as either a right adhering to citizenship or a means to achieve treatment targets is an essential first step towards systematic and meaningful integration of advocacy within the treatment system. (Contains 2 tables.)

Published
2012
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20. NK cells limit therapeutic vaccine–induced CD8 + T cell immunity in a PD-L1–dependent manner

Author

Diniz, Mariana O., primary, Schurich, Anna, additional, Chinnakannan, Senthil K., additional, Duriez, Marion, additional, Stegmann, Kerstin A., additional, Davies, Jessica, additional, Kucykowicz, Stephanie, additional, Suveizdyte, Kornelija, additional, Amin, Oliver E., additional, Alcock, Frances, additional, Cargill, Tamsin, additional, Barnes, Eleanor, additional, and Maini, Mala K., additional

Published
2022
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22. Outcomes following SARS-CoV-2 infection in patients with chronic liver disease: An international registry study

Author

European Association for the Study of the Liver, National Institutes of Health (US), North Carolina State University, National Institute for Health Research (UK), National Health Service (UK), Marjot, Thomas, Moon, Andrew M., Cook, Jonathan A., Abd-Elsalam, Sherief, Aloman, Costica, Armstrong, Matthew J., Pose, Elisa, Brenner, Erica J., Cargill, Tamsin, Catana, Maria-Andreea, Dhanasekaran, Renumathy, Eshraghian, Ahad, García-Juárez, Ignacio, Gill, Upkar S., Jones, Patricia D., Kennedy, James, Marshall, Aileen, Matthews, Charmaine, Mells, George, Mercer, Carolyn, Perumalswami, Ponni V., Avitabile, Emma, Qi, Xialong, Su, Feng, Ufere, Nneka N., Wong, Yu Jun, Zheng, Ming-Hua, Barnes, Eleanor, Barritt, Alfred S., Webb, Gwilym J., European Association for the Study of the Liver, National Institutes of Health (US), North Carolina State University, National Institute for Health Research (UK), National Health Service (UK), Marjot, Thomas, Moon, Andrew M., Cook, Jonathan A., Abd-Elsalam, Sherief, Aloman, Costica, Armstrong, Matthew J., Pose, Elisa, Brenner, Erica J., Cargill, Tamsin, Catana, Maria-Andreea, Dhanasekaran, Renumathy, Eshraghian, Ahad, García-Juárez, Ignacio, Gill, Upkar S., Jones, Patricia D., Kennedy, James, Marshall, Aileen, Matthews, Charmaine, Mells, George, Mercer, Carolyn, Perumalswami, Ponni V., Avitabile, Emma, Qi, Xialong, Su, Feng, Ufere, Nneka N., Wong, Yu Jun, Zheng, Ming-Hua, Barnes, Eleanor, Barritt, Alfred S., and Webb, Gwilym J.

Abstract

Background & Aims: Chronic liver disease (CLD) and cirrhosis are associated with immune dysregulation, leading to concerns that affected patients may be at risk of adverse outcomes following SARS-CoV-2 infection. We aimed to determine the impact of COVID-19 on patients with pre-existing liver disease, which currently remains ill-defined. Methods: Between 25th March and 8th July 2020, data on 745 patients with CLD and SARS-CoV-2 (including 386 with and 359 without cirrhosis) were collected by 2 international registries and compared to data on non-CLD patients with SARS-CoV-2 from a UK hospital network. Results: Mortality was 32% in patients with cirrhosis compared to 8% in those without (p <0.001). Mortality in patients with cirrhosis increased according to Child-Pugh class (A [19%], B [35%], C [51%]) and the main cause of death was from respiratory failure (71%). After adjusting for baseline characteristics, factors associated with death in the total CLD cohort were age (odds ratio [OR] 1.02; 1.01–1.04), Child-Pugh A (OR 1.90; 1.03–3.52), B (OR 4.14; 2.4–7.65), or C (OR 9.32; 4.80–18.08) cirrhosis and alcohol-related liver disease (OR 1.79; 1.03–3.13). Compared to patients without CLD (n = 620), propensity-score-matched analysis revealed significant increases in mortality in those with Child-Pugh B (+20.0% [8.8%–31.3%]) and C (+38.1% [27.1%–49.2%]) cirrhosis. Acute hepatic decompensation occurred in 46% of patients with cirrhosis, of whom 21% had no respiratory symptoms. Half of those with hepatic decompensation had acute-on-chronic liver failure. Conclusions: In the largest such cohort to date, we demonstrate that baseline liver disease stage and alcohol-related liver disease are independent risk factors for death from COVID-19. These data have important implications for the risk stratification of patients with CLD across the globe during the COVID-19 pandemic. Lay summary: This international registry study demonstrates that patients with cirrhosis are at increased

Published
2021

23. High mortality rates for SARS-CoV-2 infection in patients with pre-existing chronic liver disease and cirrhosis: Preliminary results from an international registry

Author

Moon, Andrew M., Webb, Gwilym J., Aloman, Costica, Armstrong, Matthew J., Cargill, Tamsin, Dhanasekaran, Renumathy, Genescà, Joan, Gill, Upkar S., James, Theodore W., Jones, Patricia D., Marshall, Aileen, Mells, George, Perumalswami, Ponni V., Qi, Xiaolong, Su, Feng, Ufere, Nneka N., Barnes, Eleanor, Barritt, A. Sidney, and Marjot, Thomas

Published
2020
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26. The Design and Development of a Multi-HBV Antigen Encoded in Chimpanzee Adenoviral and Modified Vaccinia Ankara Viral Vectors

Author

Chinnakannan, Senthil K., Cargill, Tamsin N., Donnison, Timothy A., Ansari, M. Azim, Sebastian, Sarah, Lee, Lian Ni, Hutchings, Claire, Klenerman, Paul, Maini, Mala K., Evans, Tom, and Barnes, Eleanor

Subjects
T cell vaccine, ChAd, modified vaccinia Ankara, viruses, virus diseases, Hepatitis B virus (HBV), ChAdOx1, therapeutic HBV vaccine, MVA, chimpanzee adenovirus, digestive system diseases
Abstract

Chronic hepatitis B virus (HBV) infection affects 257 million people globally. Current therapies suppress HBV but viral rebound occurs on cessation of therapy, novel therapeutic strategies are urgently required. To develop a therapeutic HBV vaccine that can induce high magnitude T cells to all major HBV antigens, we have developed a novel HBV vaccine using chimpanzee adenovirus (ChAd) and modified vaccinia Ankara (MVA) viral vectors encoding multiple HBV antigens. ChAd vaccine alone generated very high magnitude HBV specific T cell responses to all HBV major antigens. The inclusion of a shark Invariant (SIi) chain genetic adjuvant significantly enhanced the magnitude of T-cells against HBV antigens. Compared to ChAd alone vaccination, ChAd-prime followed by MVA-boost vaccination further enhanced the magnitude and breadth of the vaccine induced T cell response. Intra-cellular cytokine staining study showed that HBV specific CD8+ and CD4+ T cells were polyfunctional, producing combinations of IFN&gamma, TNF-&alpha, and IL-2. In summary, we have generated genetically adjuvanted ChAd and MVA vectored HBV vaccines with the potential to induce high-magnitude T cell responses through a prime-boost therapeutic vaccination approach. These pre-clinical studies pave the way for new studies of HBV therapeutic vaccination in humans with chronic hepatitis B infection.

Published
2020
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27. NK cells limit therapeutic vaccine–induced CD8+T cell immunity in a PD-L1–dependent manner.

Author

Diniz, Mariana O., Schurich, Anna, Chinnakannan, Senthil K., Duriez, Marion, Stegmann, Kerstin A., Davies, Jessica, Kucykowicz, Stephanie, Suveizdyte, Kornelija, Amin, Oliver E., Alcock, Frances, Cargill, Tamsin, Barnes, Eleanor, and Maini, Mala K.

Subjects
KILLER cells, CHRONIC hepatitis B, VACCINE effectiveness, T cells, HEPATITIS B virus, IMMUNITY, NUDGE theory
Abstract

A better understanding of mechanisms that regulate CD8+T cell responses to therapeutic vaccines is needed to develop approaches to enhance vaccine efficacy for chronic viral infections and cancers. We show here that NK cell depletion enhanced antigen-specific T cell responses to chimp adenoviral vector (ChAdOx) vaccination in a mouse model of chronic HBV infection (CHB). Probing the mechanism underlying this negative regulation, we observed that CHB drove parallel up-regulation of programmed cell death ligand 1 (PD-L1) on liver-resident NK cells and programmed cell death 1 (PD-1) on intrahepatic T cells. PD-L1–expressing liver-resident NK cells suppressed PD-1hiCD8+T cells enriched within the HBV-specific response to therapeutic vaccination. Cytokine activation of NK cells also induced PD-L1, and combining cytokine activation with PD-L1 blockade resulted in conversion of NK cells into efficient helpers that boosted HBV-specific CD8+T cell responses to therapeutic vaccination in mice and to chronic infection in humans. Our findings delineate an immunotherapeutic combination that can boost the response to therapeutic vaccination in CHB and highlight the broader importance of PD-L1–dependent regulation of T cells by cytokine-activated NK cells. NK cells nudge vaccine response: Therapeutic vaccines for chronic infections have reduced efficacy because of the presence of exhausted T cells and a tolerogenic environment that limits vaccine responses. Diniz et al. observed that NK cell depletion enhanced T cell responses to a chimp adenoviral vectored hepatitis B virus (HBV) vaccine in a mouse model of chronic hepatitis B virus (CHB) infection. CHB was associated with up-regulation of PD-1 on intrahepatic CD8+T cells and PD-L1 on liver-resident NK cells. These NK cells suppressed HBV-specific responses of PD-1hiCD8+T cells upon vaccination. Stimulation of NK cells with activating cytokines also induced PD-L1 expression, but cytokine activation combined with PD-L1 blockade altered NK cells to function as enhancers of HBV-specific CD8+T cell responses. These findings highlight a strategy by which therapeutic vaccine responses can be restored even in tolerogenic settings. [ABSTRACT FROM AUTHOR]

Published
2022
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30. Uphill or downhill bleeding?

Author

Cargill, Zillah, primary, Cargill, Tamsin, additional, Lei, Brian, additional, Bekkali, Noor, additional, East, James, additional, and Marshall, Jonathan, additional

Published
2020
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32. A multi-disciplinary approach to igG4 related disease aids in diagnosis and management

Author

Peters, Rory, primary, Goodchild, George, additional, Martin, Harry, additional, Cargill, Tamsin, additional, Fadipe, Adetokunbo, additional, Leandro, Maria, additional, Bailey, Adam, additional, Collier, Jane D., additional, Chouhan, Manil, additional, Luqmani, Raashid, additional, Sadler, Ross, additional, Fryer, Eve, additional, Firmin, Louisa, additional, Rodriguez-Justo, Manuel, additional, Bungay, Helen, additional, Barnes, Eleanor, additional, Webster, George, additional, and Culver, Emma, additional

Published
2020
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34. Experience from the first UK inter-regional specialist multidisciplinary meeting in the diagnosis and management of IgG4-related disease

Author

Goodchild, George, primary, Peters, Rory JR, additional, Cargill, Tamsin N, additional, Martin, Harry, additional, Fadipe, Adetokunbo, additional, Leandro, Maria, additional, Bailey, Adam, additional, Collier, Jane, additional, Firmin, Louisa, additional, Chouhan, Manil, additional, Rodriguez-Justo, Manuel, additional, Sadler, Ross, additional, Chapman, Roger W, additional, Bungay, Helen, additional, Fryer, Eve, additional, David, Joel, additional, Luqmani, Raashid, additional, Barnes, Eleanor, additional, Webster, George J, additional, and Culver, Emma L, additional

Published
2020
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36. The microbiology of pleural infection in adults: a systematic review

Author

Hassan, Maged, primary, Cargill, Tamsin, additional, Harriss, Elinor, additional, Asciak, Rachelle, additional, Mercer, Rachel M., additional, Bedawi, Eihab O., additional, McCracken, David J., additional, Psallidas, Ioannis, additional, Corcoran, John P., additional, and Rahman, Najib M., additional

Published
2019
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37. PTU-100 The role of a multi-regional specialist multi-disciplinary meeting in diagnosis and management of igg4-related disease

Author

Goodchild, George, primary, Peters, Rory, additional, Cargill, Tamsin, additional, Fadipe, Adetokunbo, additional, Leando, Maria, additional, Luqmani, Raashid, additional, Sadler, Ross, additional, Fryer, Eve, additional, Firmin, Louisa, additional, Rodriguez-Justo, Manuel, additional, Bungay, Helen, additional, Barnes, Eleanor, additional, Webster, George, additional, and Culver, Emma, additional

Published
2019
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38. FRI-162-Prime-boost vaccination strategies using chimpanzee-adeno and MVA viral vectored vaccines encoding multiple HBV antigens (CPmutS) and class II invariant chain molecular adjuvants induces robust T-cell and anti-HBs antibody response in mice

Author

Cargill, Tamsin, primary, Donnison, Timothy, additional, Ansari, Azim, additional, Maini, Mala, additional, Evans, Tom, additional, Barnes, Eleanor, additional, and Chinnakannan, Senthil Kumar, additional

Published
2019
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39. Unique patterns of glycosylation in immunoglobulin subclass G4-related disease and primary sclerosing cholangitis

Author

Culver, Emma L, primary, van de Bovenkamp, Fleur S, additional, Derksen, Ninotska I L, additional, Koers, Jana, additional, Cargill, Tamsin, additional, Barnes, Eleanor, additional, de Neef, Louise A, additional, Koeleman, Carolien A M, additional, Aalberse, Rob C, additional, Wuhrer, Manfred, additional, and Rispens, Theo, additional

Published
2018
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42. Microbiology of pleural infection according to setting

Author

Hassan, Maged, primary, Cargill, Tamsin, additional, Bedawi, Eihab, additional, Corcoran, John, additional, Harriss, Elinor, additional, Asciak, Rachelle, additional, Mercer, Rachel, additional, Hallifax, Rob, additional, and Rahman, Najib, additional

Published
2018
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48. Unique patterns of glycosylation in immunoglobulin subclass G4‐related disease and primary sclerosing cholangitis.

Author

Culver, Emma L, Bovenkamp, Fleur S, Derksen, Ninotska I L, Koers, Jana, Cargill, Tamsin, Barnes, Eleanor, Neef, Louise A, Koeleman, Carolien A M, Aalberse, Rob C, Wuhrer, Manfred, and Rispens, Theo

Subjects
CHOLANGITIS, GLYCOSYLATION, IMMUNOLOGIC diseases, IMMUNOGLOBULIN G, AFFINITY chromatography, FUCOSYLATION
Abstract

Background and Aim: Immunoglobulin subclass G4‐related disease (IgG4‐RD) is characterized by an abundance of IgG4 antibodies in the serum and tissue. Glycosylation status of antibodies can impact on immune effector functions and disease pathophysiology. We sought to establish glycosylation patterns in a prospective cohort of patients with IgG4‐RD and the relationship with disease activity and response to treatment. Methods: We assessed IgG Fc‐tail and Fab‐arm glycosylation status in patients with IgG4‐RD (n = 22), disease controls with primary sclerosing cholangitis (PSC) (n = 22), and healthy controls (n = 22). Serum IgG and subclasses were quantified using ELISA. Fc and Fab glycosylation were analyzed by mass spectrometry and lectin affinity chromatography, respectively. Disease activity, organ damage, and response to treatment were assessed using the IgG4 Responder Index. Results: Immunoglobulin G Fab sialylation was increased in IgG4‐RD compared with PSC and healthy control (P = 0.01), with a preferential increase in IgG4‐specific Fab sialylation, which was independent of IgG4 Fab‐arm exchange. There was a reduction in IgG1‐specific Fc bisection and hybrid structures in IgG4‐RD (P < 0.01), which recovered upon steroid treatment and correlated with disease activity. Overall, IgG Fc galactosylation was reduced in both IgG4‐RD and PSC (P < 0.01), with a preferential reduction in IgG1‐specific sialylation and enhancement of IgG4‐specific bisection in PSC. IgG4 fucosylation and IgG1/2/3 hybrid structures negatively correlated with complement C3 and C4 levels in IgG4‐RD (P < 0.01), but not PSC. Conclusion: We report the first study showing unique antibody glycosylation status in a prospective cohort of IgG4‐RD and PSC patients, which may determine modulation of the immune system and contribute to disease pathophysiology. [ABSTRACT FROM AUTHOR]

Published
2019
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50. Elevated Serum IgG4 Levels in Diagnosis, Treatment Response, Organ Involvement, and Relapse in a Prospective IgG4-Related Disease UK Cohort

Author

Culver, Emma L, primary, Sadler, Ross, additional, Simpson, Dawn, additional, Cargill, Tamsin, additional, Makuch, Mateusz, additional, Bateman, Adrian C, additional, Ellis, Anthony J, additional, Collier, Jane, additional, Chapman, Roger W, additional, Klenerman, P, additional, Barnes, Eleanor, additional, and Ferry, Berne, additional

Published
2016
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