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102. Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2

Author

Swadling, Leo, Diniz, Mariana O., Schmidt, Nathalie M., Amin, Oliver E., Chandran, Aneesh, Shaw, Emily, Pade, Corinna, Gibbons, Joseph M., Le Bert, Nina, Tan, Anthony T., Jeffery-Smith, Anna, Tan, Cedric C. S., Tham, Christine Y. L., Kucykowicz, Stephanie, Aidoo-Micah, Gloryanne, Rosenheim, Joshua, Davies, Jessica, Johnson, Marina, Jensen, Melanie P., Joy, George, McCoy, Laura E., Valdes, Ana M., Chain, Benjamin M., Goldblatt, David, Altmann, Daniel M., Boyton, Rosemary J., Manisty, Charlotte, Treibel, Thomas A., Moon, James C., Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Andiapen, Mervyn, Artico, Jessica, Augusto, João B., Baca, Georgina L., Bailey, Sasha N. L., Bhuva, Anish N., Boulter, Alex, Bowles, Ruth, Bracken, Olivia V., O’Brien, Ben, Brooks, Tim, Bullock, Natalie, Butler, David K., Captur, Gabriella, Champion, Nicola, Chan, Carmen, Collier, David, de Sousa, Jorge Couto, Couto-Parada, Xose, Cutino-Moguel, Teresa, Davies, Rhodri H., Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Fontana, Marianna, Forooghi, Nasim, Gaier, Celia, Gilroy, Derek, Hamblin, Matt, Harker, Gabrielle, Hewson, Jacqueline, Hickling, Lauren M., Hingorani, Aroon D., Howes, Lee, Hughes, Alun, Hughes, Gemma, Hughes, Rebecca, Itua, Ivie, Jardim, Victor, Lee, Wing-Yiu Jason, Jensen, Melanie petra, Jones, Jessica, Jones, Meleri, Kapil, Vikas, Kurdi, Hibba, Lambourne, Jonathan, Lin, Kai-Min, Louth, Sarah, Mandadapu, Vineela, McKnight, Áine, Menacho, Katia, Mfuko, Celina, Mitchelmore, Oliver, Moon, Christopher, Murray, Sam M., Noursadeghi, Mahdad, Otter, Ashley, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Babita, Petersen, Steffen E., Piniera, Brian, Pieper, Franziska P., Pope, Daniel, Prossora, Mary, Rannigan, Lisa, Rapala, Alicja, Reynolds, Catherine J., Richards, Amy, Robathan, Matthew, Sambile, Genine, Semper, Amanda, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Taylor, Stephen, Temperton, Nigel J., Thomas, Stephen, Thornton, George D., Tucker, Art, Veerapen, Jessry, Vijayakumar, Mohit, Welch, Sophie, Wodehouse, Theresa, Wynne, Lucinda, Zahedi, Dan, Dorp, Lucy van, Balloux, Francois, McKnight, Áine, Bertoletti, Antonio, Maini, Mala K., Swadling, Leo [0000-0002-0537-6715], Schmidt, Nathalie M [0000-0002-9841-8418], Gibbons, Joseph M [0000-0002-7238-2381], Le Bert, Nina [0000-0003-0502-2527], Tham, Christine YL [0000-0002-2913-7591], Kucykowicz, Stephanie [0000-0002-8849-218X], Rosenheim, Joshua [0000-0003-0171-2053], McCoy, Laura E [0000-0001-9503-7946], Valdes, Ana M [0000-0003-1141-4471], Chain, Benjamin M [0000-0002-7417-3970], Goldblatt, David [0000-0002-0769-5242], Boyton, Rosemary J [0000-0002-5608-0797], van Dorp, Lucy [0000-0002-6211-2310], Balloux, Francois [0000-0003-1978-7715], Noursadeghi, Mahdad [0000-0002-4774-0853], Bertoletti, Antonio [0000-0002-2942-0485], Maini, Mala K [0000-0001-6384-1462], Apollo - University of Cambridge Repository, Medical Research Council (MRC), and Multiple Sclerosis Society

Subjects
Male, Transcription, Genetic, 631/250/1619/554, medicine.disease_cause, DISEASE, Neutralization, Cohort Studies, 13/1, 631/250/2152/1566/1571, INFECTION, Coronaviridae, Asymptomatic Infections, Polymerase, Coronavirus, Multidisciplinary, biology, article, virus diseases, DNA-Directed RNA Polymerases, Multidisciplinary Sciences, 13/31, Seroconversion, Cohort, Science & Technology - Other Topics, VIRUS, Female, 82/75, HEALTH-CARE WORKERS, Antibody, ANTIBODY-RESPONSES, General Science & Technology, Health Personnel, 13/106, IMMUNITY, Evolution, Molecular, Memory T Cells, In vivo, Multienzyme Complexes, medicine, Humans, EXPOSURE, 631/326/596/4130, COVIDsortium Investigators, Cell Proliferation, PATHOGENS, Science & Technology, SARS-CoV-2, MEMORY, CORONAVIRUSES, COVID-19, Membrane Proteins, 631/250/254, biology.organism_classification, Virology, biology.protein
Abstract

Individuals with potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) do not necessarily develop PCR or antibody positivity, suggesting that some individuals may clear subclinical infection before seroconversion. T cells can contribute to the rapid clearance of SARS-CoV-2 and other coronavirus infections1–3. Here we hypothesize that pre-existing memory T cell responses, with cross-protective potential against SARS-CoV-2 (refs. 4–11), would expand in vivo to support rapid viral control, aborting infection. We measured SARS-CoV-2-reactive T cells, including those against the early transcribed replication–transcription complex (RTC)12,13, in intensively monitored healthcare workers (HCWs) who tested repeatedly negative according to PCR, antibody binding and neutralization assays (seronegative HCWs (SN-HCWs)). SN-HCWs had stronger, more multispecific memory T cells compared with a cohort of unexposed individuals from before the pandemic (prepandemic cohort), and these cells were more frequently directed against the RTC than the structural-protein-dominated responses observed after detectable infection (matched concurrent cohort). SN-HCWs with the strongest RTC-specific T cells had an increase in IFI27, a robust early innate signature of SARS-CoV-2 (ref. 14), suggesting abortive infection. RNA polymerase within RTC was the largest region of high sequence conservation across human seasonal coronaviruses (HCoV) and SARS-CoV-2 clades. RNA polymerase was preferentially targeted (among the regions tested) by T cells from prepandemic cohorts and SN-HCWs. RTC-epitope-specific T cells that cross-recognized HCoV variants were identified in SN-HCWs. Enriched pre-existing RNA-polymerase-specific T cells expanded in vivo to preferentially accumulate in the memory response after putative abortive compared to overt SARS-CoV-2 infection. Our data highlight RTC-specific T cells as targets for vaccines against endemic and emerging Coronaviridae.

Published
2021

103. LGBTQIA+ Pride in Diversity:Panel Discussion

Author

Pert, Sean, Vakharia, Rick, Davies, Jessica, Boot, Kate, and Pasonage, Toby

Abstract

The first LGBTQIA+ panel at the Royal college of Speech and Language Therapists discussing how to make services accessible and welcoming to LGBTQIA+ staff and service users.Dr Sean Pert discusses this important issue with the UK SLT Pride Network.

Published
2021

112. Therapeutic Potential of TLR8 Agonist GS‐9688 (Selgantolimod) in Chronic Hepatitis B: Remodeling of Antiviral and Regulatory Mediators

Author

Amin, Oliver E., primary, Colbeck, Emily J., additional, Daffis, Stephane, additional, Khan, Shahzada, additional, Ramakrishnan, Dhivya, additional, Pattabiraman, Divya, additional, Chu, Ruth, additional, Micolochick Steuer, Holly, additional, Lehar, Sophie, additional, Peiser, Leanne, additional, Palazzo, Adam, additional, Frey, Christian, additional, Davies, Jessica, additional, Javanbakht, Hassan, additional, Rosenberg, William M.C., additional, Fletcher, Simon P., additional, Maini, Mala K., additional, and Pallett, Laura J., additional

Published
2021
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113. Tissue CD14+CD8+T cells reprogrammed by myeloid cells and modulated by LPS

Author

Pallett, Laura J., Swadling, Leo, Diniz, Mariana, Maini, Alexander A., Schwabenland, Marius, Gasull, Adrià Dalmau, Davies, Jessica, Kucykowicz, Stephanie, Skelton, Jessica K., Thomas, Niclas, Schmidt, Nathalie M., Amin, Oliver E., Gill, Upkar S., Stegmann, Kerstin A., Burton, Alice R., Stephenson, Emily, Reynolds, Gary, Whelan, Matt, Sanchez, Jenifer, de Maeyer, Roel, Thakker, Clare, Suveizdyte, Kornelija, Uddin, Imran, Ortega-Prieto, Ana M., Grant, Charlotte, Froghi, Farid, Fusai, Giuseppe, Lens, Sabela, Pérez-del-Pulgar, Sofia, Al-Akkad, Walid, Mazza, Giuseppe, Noursadeghi, Mahdad, Akbar, Arne, Kennedy, Patrick T. F., Davidson, Brian R., Prinz, Marco, Chain, Benjamin M., Haniffa, Muzlifah, Gilroy, Derek W., Dorner, Marcus, Bengsch, Bertram, Schurich, Anna, and Maini, Mala K.

Abstract

The liver is bathed in bacterial products, including lipopolysaccharide transported from the intestinal portal vasculature, but maintains a state of tolerance that is exploited by persistent pathogens and tumours1–4. The cellular basis mediating this tolerance, yet allowing a switch to immunity or immunopathology, needs to be better understood for successful immunotherapy of liver diseases. Here we show that a variable proportion of CD8+T cells compartmentalized in the human liver co-stain for CD14 and other prototypic myeloid membrane proteins and are enriched in close proximity to CD14highmyeloid cells in hepatic zone 2. CD14+CD8+T cells preferentially accumulate within the donor pool in liver allografts, among hepatic virus-specific and tumour-infiltrating responses, and in cirrhotic ascites. CD14+CD8+T cells exhibit increased turnover, activation and constitutive immunomodulatory features with high homeostatic IL-10 and IL-2 production ex vivo, and enhanced antiviral/anti-tumour effector function after TCR engagement. This CD14+CD8+T cell profile can be recapitulated by the acquisition of membrane proteins—including the lipopolysaccharide receptor complex—from mononuclear phagocytes, resulting in augmented tumour killing by TCR-redirected T cells in vitro. CD14+CD8+T cells express integrins and chemokine receptors that favour interactions with the local stroma, which can promote their induction through CXCL12. Lipopolysaccharide can also increase the frequency of CD14+CD8+T cells in vitro and in vivo, and skew their function towards the production of chemotactic and regenerative cytokines. Thus, bacterial products in the gut–liver axis and tissue stromal factors can tune liver immunity by driving myeloid instruction of CD8+T cells with immunomodulatory ability.

Published
2023
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117. Predicting benefit of radium 223 based on biochemical response and site of metastasis: A real life multicenter UK study.

Author

Das, Prantik, primary, Davies, Jessica, additional, Sharma, Anand, additional, Nair, Ajith, additional, Vengalil, Salil, additional, Perna, Carla, additional, Branagan, Jenny, additional, Masters, Benjamin, additional, Goh, Chee, additional, Otter, Sophie, additional, Prakash, Vineet, additional, and Singh, Sadmeet, additional

Published
2021
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119. Parental-fetal interplay of immune genes leads to intrauterine growth restriction

Author

Kaur, Gurman, primary, Porter, Caroline B. M., additional, Ashenberg, Orr, additional, Lee, Jack, additional, Riesenfeld, Samantha J., additional, Hofree, Matan, additional, Aggelakopoulou, Maria, additional, Subramanian, Ayshwarya, additional, Kuttikkatte, Subita Balaram, additional, Attfield, Kathrine E., additional, Desel, Christiane A. E., additional, Davies, Jessica L., additional, Evans, Hayley G., additional, Avraham-Davidi, Inbal, additional, Nguyen, Lan T., additional, Dionne, Danielle A., additional, Neumann, Anna E., additional, Jensen, Lise Torp, additional, Barber, Thomas R., additional, Soilleux, Elizabeth, additional, Carrington, Mary, additional, McVean, Gil, additional, Rozenblatt-Rosen, Orit, additional, Regev, Aviv, additional, and Fugger, Lars, additional

Published
2021
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127. 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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128. Young Peoples' Perspectives on the Role of Harm Reduction Techniques in the Management of Their Self-Harm: A Qualitative Study.

Author

Davies, Jessica, Pitman, Alexandra, Bamber, Victoria, Billings, Joanne, and Rowe, Sarah

Abstract

Self-harm is a common phenomenon amongst young people, often used to regulate emotional distress. Over the last decade harm reduction approaches to self-harm have been introduced as a means to minimize risk and reinforce alternative coping strategies. However, there is a stark absence of research into the perceived usefulness of such techniques amongst adolescents, and previous studies have highlighted ethical concerns about advocating 'safer' forms of self-harm. This study aimed to investigate the perceived usefulness of harm reduction techniques for adolescents who self-harm. We purposively recruited current clients of a British early intervention program supporting young people in managing self-harm. We conducted semi-structured interviews and analyzed transcripts using thematic analysis. Eleven interviews with service users aged 14–15 years identified three main themes: (1) Controlling the uncontrollable; (2) Barriers to practising safer self-harm; and (3) Developing a broad repertoire of harm reduction techniques. Participants expressed mixed views regarding the usefulness of such approaches. Some described greater competence and empowerment in self-harm management, whilst others described the utility of harm reduction methods as either short-lived or situation-specific, with the potential for misuse of anatomical knowledge to cause further harm to high-risk adolescents. The findings from our sample suggest harm reduction techniques have a place in self-harm management for some individuals, but their usage should be monitored and offered alongside alternative strategies and therapeutic support. Our study highlights the need for further research on who would benefit from these techniques and how they can be implemented successfully. Harm reduction can help people who self–harm manage distress and maintain autonomy People who self-harm have a broad repertoire of harm reduction techniques Harm reduction can help reduce long-term damage and frequency of self-harm [ABSTRACT FROM AUTHOR]

Published
2022
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130. L-selectin regulates human neutrophil transendothelial migration

Author

Rahman, Izajur, primary, Collado Sánchez, Aida, additional, Davies, Jessica, additional, Rzeniewicz, Karolina, additional, Abukscem, Sarah, additional, Joachim, Justin, additional, Hoskins Green, Hannah L., additional, Killock, David, additional, Sanz, Maria Jesus, additional, Charras, Guillaume, additional, Parsons, Maddy, additional, and Ivetic, Aleksandar, additional

Published
2021
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133. Therapeutically expanded human regulatory T-cells are super- suppressive due to HIF1A induced expression of CD73.

Author

Jarvis, Lorna, primary, Rainbow, Daniel, additional, Coppard, Valerie, additional, Howlett, Sarah, additional, Davies, Jessica, additional, Mullay, Harpreet, additional, Hester, Joanna, additional, Ashmore, Tom, additional, Bosch, Aletta Van Den, additional, Grist, James, additional, Coles, Alasdair, additional, Mousa, Hani, additional, Pluchino, Stefano, additional, Mahbubani, Krishnaa, additional, Griffin, Julian, additional, Saeb-Parsy, Kourosh, additional, Issa, Fadi, additional, Peruzzotti-Jametti, Luca, additional, Wicker, Linda, additional, and Jones, Joanne, additional

Published
2020
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140. Life Expectancies: Late Victorian Literature and the Biopolitics of Empire

Author

Davies, Jessica Leigh

Subjects
Literature, British & Irish, biology, colonialism, nineteenth century, politics, power
Abstract

By the end of the nineteenth century, the rise of evolutionary thinking had produced a radical new understanding of life as the underlying connectedness of all living beings. If only the fittest would survive, the problem was no longer about how to differentiate between species, as it had been for the philosophical tradition since Aristotle, but how to articulate differences within a species. This dissertation analyzes the complex relationship between biology, politics and power that emerged in late Victorian literature. I examine the ways in which biological thinking was never limited to biology itself, nor was it a metaphorical technique used to describe social relations or simply a way to transcribe a political discourse into biological terms. I argue that the difference between biology and politics completely collapsed, and that this indistinguishability functioned to expand and justify British colonialism. Inspired by Michel Foucault's work on biopower, I demonstrate and expand his theory of nineteenth century biopolitics as a form of power that takes biological life as both its subject and object through a series of regulatory controls leveraged at entire populations. It is a power characterized not by the threat of death, but its ability to optimize and foster biological life. Reproduction, mortality, life expectancy, and the management of health and disease are just some of the biological processes that fall under the dominion of this disciplinary power, with sexuality emerging as a particularly dense transfer point in the investment of the life of the population. I trace this notion of biopolitics through late Victorian literature - through the novels of Oscar Wilde, Richard Marsh and H. Rider Haggard - in which the investment in thinking biologically about sexuality is clear. Yet my central argument is that biopower cannot operate without empire. The reality of empire and all of the technologies and categories of difference that were central to its expansion and justification - such as gender, race and class - were inextricable with the biopower that took sexuality as its subject and object. Colonialism is not a marginalized technology of nineteenth century biopower; biopower is colonial.My dissertation expands the critical conversation about late Victorian literature beyond the psychoanalytic, postcolonial and new historicist methodologies that have characterized the debates to ask a different set of questions. It was not my methodology that determined the questions, but a set of questions in the texts that suggested the most useful methodology for reading them. I pull insights from multiple fields of knowledge production beyond literature itself - including philosophy, post-colonial theory, anthropology, history, feminist theory, queer theory, and critical science and race studies. Beginning with Wilde, I trace sexuality as a discursive node of biopower that produces the homosexual "as a species." I then link this project of "species-making" to the rise of biological racism that imagined colonial populations quite literally as insects, functioning as a justification for war and "extermination." The final chapter analyzes the ways in which these "new species" provided the material for an imperial bioeconomy. I argue that this bioeconomy operated by imagining life in the colonies as expendable in relation to life in Britain, in order to produce wealth at home and regenerate the nation. These arguments trace a transnational itinerary through the discourses of decadence, degeneration, colonialism and imperialism, moving from and between Europe, Egypt, South America and southern Africa, to look several of the most aggressive components of the nineteenth century science of life: vivisection, mimicry and vaccination. I demonstrate that speaking about biological life simultaneously demands that we speak about the most profound set of differences - between nature and technology, humans and animals, and the differences we make real within our own species world. If categories such as race, sexuality, gender, class and empire mattered so much to the Victorians, they continue to matter now because biological thinking threatens to carry with it the trace of the violence of difference itself.

Published
2010

150. An integrated platform to systematically identify causal variants and genes for polygenic human traits

Author

Downes, Damien J., primary, Schwessinger, Ron, additional, Hill, Stephanie J., additional, Nussbaum, Lea, additional, Scott, Caroline, additional, Gosden, Matthew E., additional, Hirschfeld, Priscila P., additional, Telenius, Jelena M., additional, Eijsbouts, Chris Q., additional, McGowan, Simon J., additional, Cutler, Antony J., additional, Kerry, Jon, additional, Davies, Jessica L., additional, Dendrou, Calliope A., additional, Inshaw, Jamie R.J., additional, Larke, Martin S.C., additional, Marieke Oudelaar, A., additional, Bozhilov, Yavor, additional, King, Andrew J., additional, Brown, Richard C., additional, Suciu, Maria C., additional, Davies, James O.J., additional, Hublitz, Philip, additional, Fisher, Chris, additional, Kurita, Ryo, additional, Nakamura, Yukio, additional, Lunter, Gerton, additional, Taylor, Stephen, additional, Buckle, Veronica J., additional, Todd, John A., additional, Higgs, Douglas R., additional, and Hughes, Jim R., additional

Published
2019
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