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1. Design, Immunogenicity and Preclinical Efficacy of the ChAdOx1.COVconsv12 Pan-Sarbecovirus T-Cell Vaccine.

Author

Wee, Edmund G.-T., Kempster, Sarah, Ferguson, Deborah, Hall, Joanna, Ham, Claire, Morris, Susan, Crook, Alison, Gilbert, Sarah C., Korber, Bette, Almond, Neil, and Hanke, Tomáš

Subjects
COVID-19 pandemic, GOLDEN hamster, T cells, SARS-CoV-2, COVID-19 vaccines
Abstract

During the COVID-19 pandemic, antibody-based vaccines targeting the SARS-CoV-2 spike glycoprotein were the focus for development because neutralizing antibodies were associated with protection against the SARS-CoV-2 infection pre-clinically and in humans. While deploying these spike-based vaccines saved millions of lives worldwide, it has become clear that the immunological mechanisms of protection against severe disease are multifaceted and involve non-neutralizing antibody components. Here, we describe a novel pan-sarbecovirus T-cell vaccine, ChAdOx1.COVconsv12, designed to complement and broaden the protection of spike vaccines. The vaccine immunogen COVconsv12 employs the two regions in the viral proteome most conserved among sarbecoviruses, which are delivered by replication-deficient vector ChAdOx1. It directs T cells towards epitopes shared among sarbecoviruses including evolving SARS-CoV-2 variants. Here, we show that ChAdOx1.COVconsv12 induced broad T-cell responses in the BALB/c and C57BL/6 mice. In the Syrian hamster challenge model, ChAdOx1.COVconsv12 alone did not protect against the SARS-CoV-2 infection, but when co-administered with 1/50th of the ChAdOx1 nCoV-19 spike vaccine protective dose, faster recovery and lower oral swab viral load were observed. Induction of CD8+ T cells may decrease COVID-19 severity and extend the T-cell response coverage of variants to match the known (and as yet unknown) members of the β-coronavirus family. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Marine bivalve records of Antarctic seasonality and biological responses to environmental change over the Cretaceous-Paleogene mass extinction interval

Author

Hall, Joanna Louise Ong, Francis, Jane, Haywood, Alan, Newton, Rob, Hunter, Stephen, Crame, Alistair, and Harper, Liz

Subjects
551.46
Abstract

The Cretaceous-Paleogene mass extinction event occurred 66 million years ago and had a profound effect on the course of evolutionary history, with the extinction of up to 75% of life and larger effects on the broader Earth system. A number of studies posit that the severity of this extinction event may have been amplified by climate variability and destabilisation in the latest Cretaceous – immediately prior to the extinction event. The strong seasonal forcing in the polar high latitudes is likely to have enhanced any such effects during this time period; additionally, the historical mismatch between late Cretaceous proxy data and climate simulations is particularly pronounced at high latitudes and both the effects of a stronger seasonal cycle on proxy temperature conversions, and misrepresentation of seasonality in climate models have been suggested as factors in the mismatch. This makes the Antarctic an extremely valuable location to study with regards to seasonality from a proxy- and model- based perspective. Seymour Island is a rare and valuable Antarctic K-Pg boundary site with a good framework of fossil, stratigraphic and sedimentological study, which makes fossil material ideal for investigation of the effects and impacts of seasonality and environmental change across the mass extinction interval. This thesis presents a detailed study focusing on using fossil bivalve shell material from the Seymour Island section to reconstruct records of Antarctic climate and seasonality across the K-Pg mass extinction event. New data were obtained about the seasonal growth patterns of these bivalves to understand their growth and ontogenetic response to potential climate variability and the effects of the mass extinction. For the first time, sub-annual resolution stable carbon and oxygen isotopic data were produced from Seymour Island’s bivalve shells to show seasonal changes in temperatures and detect changes in biogeochemical cycling and methane influence through the section. These data were integrated with a series of oxygen isotope enabled climate simulations to address potential issues converting from isotopic to temperature data in a highly seasonal environment and provide further information regarding the influence of sea ice. Combining new proxy- and model- based knowledge in a series of sensitivity experiments, it was shown that both sets of data display good agreement under realistic sets of parameters, suggesting that seasonality was important for the development of polar ecosystems. Warm summer temperatures may have been key in permitting the ecological strategy in these bivalves of slow growth to large sizes, which in turn may have contributed to survivorship across the K-Pg boundary.

Published
2017

4. Heterocorporealities : popular dance and cultural hybridity in UK drum 'n' bass club culture

Author

Hall, Joanna Louise

Subjects
306
Abstract

In this thesis I examine popular dance practice within contemporary UK Drum ‘n’ Bass club culture. Despite an active focus by cultural analysts on club and rave events where dancing is the central focus and ‘dance music’ is played, the dancing body is noticeably absent from previous discussion. I provide a discursive framework for the introduction of the dancing body into club cultural research by documenting and examining the dance practices in one specific genre of dance music: Drum ‘n’ Bass. Drum ‘n’ Bass is a sub-genre of electronic dance music that first developed in the UK in the early 1990s with its origins in US Hip Hop, Detroit and European Techno, and Jamaican Reggae and Ragga. In this thesis I argue that the intertextual, inter-generic and inter-cultural development of Drum ‘n’ Bass musical and clubbing culture is represented in the dancing body. I situate dancing as the central way in which Drum ‘n’ Bass club-goers construct, perform and reiterate specific personal and collective identities, which are informed, although not defined, by the musical genre’s history. Empirical research examining the popular dance practices within contemporary Drum ‘n’ Bass club culture reveals complex networks of association with, and dissociation from, other ‘dance music’ and Drum ‘n’ Bass clubbing crowds, which is demonstrated through the ‘appropriation’ and revaluation of specific racial, class-based and gendered identities. My central hypothesis is that the Drum ‘n’ Bass dancing body is heterocorporeal: a hybridized body where knowledge and beliefs about cultural groups, articulated in terms of class, race, gender, age and sexuality, actively intersect to create new meaning and significance through dance. The thesis is structured into two parts; in Part One I examine discourse regarding the construction and performance of identity in contemporary youth cultures and in Part Two I analyse fieldwork data from Drum ‘n’ Bass club culture.

Published
2009

11. Atkins v. Virginia: national consensus or six-person opinion?

Author

Hall, Joanna

Subjects
Cruel and unusual punishment -- Laws, regulations and rules, Capital punishment -- Laws, regulations and rules, Mentally disabled persons -- Laws, regulations and rules, Capital punishment for mentally handicapped -- Laws, regulations and rules, Capital punishment for juvenile offenders -- Laws, regulations and rules, Capital punishment in mass media -- Laws, regulations and rules, Atkins v. Virginia (536 U.S. 304 (2002)), Government regulation, United States Constitution (U.S. Const. amend. 8)
Published
2004

13. Iridescence as Camouflage

Author

Kjernsmo, Karin, primary, Whitney, Heather M., additional, Scott-Samuel, Nicholas E., additional, Hall, Joanna R., additional, Knowles, Henry, additional, Talas, Laszlo, additional, and Cuthill, Innes C., additional

Published
2020
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15. Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model

Author

Page Mark, Stebbings Richard, Berry Neil, Hull Robin, Ferguson Deborah, Davis Leanne, Duffy Laura, Elsley William, Hall Joanna, Ham Claire, Hassall Mark, Li Bo, Mee Edward T, Quartey-Papafio Ruby, Rose Nicola J, Mathy Nathalie, Voss Gerald, Stott E, and Almond Neil

Subjects
Envelope HIV-1 vaccine, Recombinant gp120, Macaque model, SHIV, Heterologous challenge, Protection, Cynomolgus macaque, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Current data suggest that an efficacious human immunodeficiency virus type 1 (HIV-1) vaccine should elicit both adaptive humoral and cell mediated immune responses. Such a vaccine will also need to protect against infection from a range of heterologous viral variants. Here we have developed a simian-human immunodeficiency virus (SHIV) based model in cynomolgus macaques to investigate the breadth of protection conferred by HIV-1W61D recombinant gp120 vaccination against SHIVsbg and SHIVSF33 challenge, and to identify correlates of protection. Results High titres of anti-envelope antibodies were detected in all vaccinees. The antibodies reacted with both the homologous HIV-1W61D and heterologous HIV-1IIIB envelope rgp120 which has an identical sequence to the SHIVsbg challenge virus. Significant titres of virus neutralising antibodies were detected against SHIVW61D expressing an envelope homologous with the vaccine, but only limited cross neutralisation against SHIVsbg, SHIV-4 and SHIVSF33 was observed. Protection against SHIVsbg infection was observed in vaccinated animals but none was observed against SHIVSF33 challenge. Transfer of immune sera from vaccinated macaques to naive recipients did not confer protection against SHIVsbg challenge. In a follow-up study, T cell proliferative responses detected after immunisation with the same vaccine against a single peptide present in the second conserved region 2 of HIV-1 W61D and HIV-1 IIIB gp120, but not SF33 gp120. Conclusions Following extended vaccination with a HIV-1 rgp120 vaccine, protection was observed against heterologous virus challenge with SHIVsbg, but not SHIVSF33. Protection did not correlate with serological responses generated by vaccination, but might be associated with T cell proliferative responses against an epitope in the second constant region of HIV-1 gp120. Broader protection may be obtained with recombinant HIV-1 envelope based vaccines formulated with adjuvants that generate proliferative T cell responses in addition to broadly neutralising antibodies.

Published
2012
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16. Rapid and iterative genome editing in the malaria parasite Plasmodium knowlesi provides new tools for P. vivax research

Author

Mohring, Franziska, primary, Hart, Melissa Natalie, additional, Rawlinson, Thomas A, additional, Henrici, Ryan, additional, Charleston, James A, additional, Diez Benavente, Ernest, additional, Patel, Avnish, additional, Hall, Joanna, additional, Almond, Neil, additional, Campino, Susana, additional, Clark, Taane G, additional, Sutherland, Colin J, additional, Baker, David A, additional, Draper, Simon J, additional, and Moon, Robert William, additional

Published
2019
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17. Vaccination with live attenuated simian immunodeficiency virus causes dynamic changes in intestinal CD4+CCR5+ T cells

Author

Elsley William, Quartey-Papafio Ruby, Page Mark, Hall Joanna, Smith Deborah, Ferguson Deborah, Ham Claire, Berry Neil, Li Bo, Robinson Mark, Almond Neil, and Stebbings Richard

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Vaccination with live attenuated SIV can protect against detectable infection with wild-type virus. We have investigated whether target cell depletion contributes to the protection observed. Following vaccination with live attenuated SIV the frequency of intestinal CD4+CCR5+ T cells, an early target of wild-type SIV infection and destruction, was determined at days 3, 7, 10, 21 and 125 post inoculation. Results In naive controls, modest frequencies of intestinal CD4+CCR5+ T cells were predominantly found within the LPL TTrM-1 and IEL TTrM-2 subsets. At day 3, LPL and IEL CD4+CCR5+ TEM cells were dramatically increased whilst less differentiated subsets were greatly reduced, consistent with activation-induced maturation. CCR5 expression remained high at day 7, although there was a shift in subset balance from CD4+CCR5+ TEM to less differentiated TTrM-2 cells. This increase in intestinal CD4+CCR5+ T cells preceded the peak of SIV RNA plasma loads measured at day 10. Greater than 65.9% depletion of intestinal CD4+CCR5+ T cells followed at day 10, but overall CD4+ T cell homeostasis was maintained by increased CD4+CCR5- T cells. At days 21 and 125, high numbers of intestinal CD4+CCR5- naive TN cells were detected concurrent with greatly increased CD4+CCR5+ LPL TTrM-2 and IEL TEM cells at day 125, yet SIV RNA plasma loads remained low. Conclusions This increase in intestinal CD4+CCR5+ T cells, following vaccination with live attenuated SIV, does not correlate with target cell depletion as a mechanism of protection. Instead, increased intestinal CD4+CCR5+ T cells may correlate with or contribute to the protection conferred by vaccination with live attenuated SIV.

Published
2011
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18. High benthic methane flux in low sulfate oceans: Evidence from carbon isotopes in Late Cretaceous Antarctic bivalves

Author

Hall, Joanna L.O., Newton, Robert J., Witts, James D., Francis, Jane E., Hunter, Stephen J., Jamieson, Robert A., Harper, Elizabeth M., Crame, J. Alistair, Haywood, Alan M., Hall, Joanna L.O., Newton, Robert J., Witts, James D., Francis, Jane E., Hunter, Stephen J., Jamieson, Robert A., Harper, Elizabeth M., Crame, J. Alistair, and Haywood, Alan M.

Abstract

The shell material of marine benthic bivalves provides a sensitive archive of water chemistry immediately above the sediment–water interface, which in turn is affected by sedimentary geochemistry and redox reactions. Sulfate has a major controlling effect on sedimentary carbon cycling, particularly the processes of methane production and oxidation, with lower concentrations of sulfate likely resulting in an increase in sedimentary methane production. Whilst it is accepted that ocean sulfate varied markedly across the Phanerozoic, evidence of changes in methane production in sediments has so far been lacking. There is potential for the oxidation products of sedimentary methane to be preserved and detected in marine fossils. Here we present the results of high resolution carbonate isotope records from two taxa of well-preserved shallow-infaunal bivalve (Lahillia and Cucullaea) collected from the marine shelf succession across the Cretaceous–Paleogene (K–Pg) boundary in Seymour Island, Antarctica. The succession has pre-existing subtle indications of more abundant methane, and the time period is characterized by much lower marine sulfate concentrations than modern. These shell carbonate–carbon isotope records vary widely: at one extreme, shells have typical average values and small ranges compatible with a contemporaneous marine dissolved inorganic carbon (DIC) source and modern-style sedimentary carbon cycling. At the other, the shells have large-amplitude annual cycles of carbon isotopic variability of up to 23.8‰ within a single year of growth and shell carbonate δ13δ13C compositions as negative as −34‰. Shells with these increased ranges and unusually negative values are found at discrete intervals and across both bivalve taxa. The contribution of methane required to explain the most negative carbonate–carbon isotopic values in the bivalve shells is extremely high (between 30 to 85% of bottom-water DIC based on mass balance calculations). Records of organic-carbon

Published
2018

19. The impact of the Cretaceous–Paleogene (K–Pg) mass extinction event on the global sulfur cycle: Evidence from Seymour Island, Antarctica

Author

Witts, James D., Newton, Robert J., Mills, Benjamin J.W., Wignall, Paul B., Bottrell, Simon H., Hall, Joanna L.O., Francis, Jane E., Crame, J. Alistair, Witts, James D., Newton, Robert J., Mills, Benjamin J.W., Wignall, Paul B., Bottrell, Simon H., Hall, Joanna L.O., Francis, Jane E., and Crame, J. Alistair

Abstract

The Cretaceous–Paleogene (K–Pg) mass extinction event 66 million years ago led to large changes to the global carbon cycle, primarily via a decrease in primary or export productivity of the oceans. However, the effects of this event and longer-term environmental changes during the Late Cretaceous on the global sulfur cycle are not well understood. We report new carbonate associated sulfate (CAS) sulfur isotope data derived from marine macrofossil shell material from a highly expanded high latitude Maastrichtian to Danian (69–65.5 Ma) succession located on Seymour Island, Antarctica. These data represent the highest resolution seawater sulfate record ever generated for this time interval, and are broadly in agreement with previous low-resolution estimates for the latest Cretaceous and Paleocene. A vigorous assessment of CAS preservation using sulfate oxygen, carbonate carbon and oxygen isotopes and trace element data, suggests factors affecting preservation of primary seawater CAS isotopes in ancient biogenic samples are complex, and not necessarily linked to the preservation of original carbonate mineralogy or chemistry. Primary data indicate a generally stable sulfur cycle in the early-mid Maastrichtian (69 Ma), with some fluctuations that could be related to increased pyrite burial during the ‘mid-Maastrichtian Event’. This is followed by an enigmatic +4‰ increase in δ34SCAS during the late Maastrichtian (68 to 66 Ma), culminating in a peak in values in the immediate aftermath of the K–Pg extinction which may be related to temporary development of oceanic anoxia in the aftermath of the Chicxulub bolide impact. There is no evidence of the direct influence of Deccan volcanism on the seawater sulfate isotopic record during the late Maastrichtian, nor of a direct influence by the Chicxulub impact itself. During the early Paleocene (magnetochron C29R) a prominent negative excursion in seawater δ34S of 3–4‰ suggests that a global decline in organic carbon burial related

Published
2018

20. Dynamic Dazzle Distorts Speed Perception

Author

Hall, Joanna R., primary, Cuthill, Innes C., additional, Baddeley, Roland, additional, Attwood, Angela S., additional, Munafò, Marcus R., additional, and Scott-Samuel, Nicholas E., additional

Published
2016
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24. Heavy focus on new clients hits bottom line A recent survey indicates the 'sell and move on' approach of most financial services organisations also leads to missed opportunities, says Joanna Hall

Author

Hall, Joanna

Subjects
Financial planners -- Surveys, Banking, finance and accounting industries, Business, Business, international
Abstract

The provision of regular advice to clients is an exception rather than the rule for many advisory organisations. This finding was clearly evident in a recent survey of the UK [...]

Published
2007

25. Immunogenicity of a Recombinant Measles-HIV-1 Clade B Candidate Vaccine

Author

Stebbings, Richard, primary, Février, Michèle, additional, Li, Bo, additional, Lorin, Clarisse, additional, Koutsoukos, Marguerite, additional, Mee, Edward, additional, Rose, Nicola, additional, Hall, Joanna, additional, Page, Mark, additional, Almond, Neil, additional, Voss, Gerald, additional, and Tangy, Frédéric, additional

Published
2012
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26. Vaccination with live attenuated simian immunodeficiency virus causes dynamic changes in intestinal CD4+CCR5+ T cells

Author

Li, Bo, primary, Berry, Neil, additional, Ham, Claire, additional, Ferguson, Deborah, additional, Smith, Deborah, additional, Hall, Joanna, additional, Page, Mark, additional, Quartey-Papafio, Ruby, additional, Elsley, William, additional, Robinson, Mark, additional, Almond, Neil, additional, and Stebbings, Richard, additional

Published
2011
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27. CD8 + Lymphocytes Do Not Mediate Protection against Acute Superinfection 20 Days after Vaccination with a Live Attenuated Simian Immunodeficiency Virus

Author

Stebbings, Richard, primary, Berry, Neil, additional, Waldmann, Herman, additional, Bird, Pru, additional, Hale, Geoff, additional, Stott, Jim, additional, North, David, additional, Hull, Robin, additional, Hall, Joanna, additional, Lines, Jenny, additional, Brown, Stuart, additional, D'Arcy, Nikki, additional, Davis, Leanne, additional, Elsley, William, additional, Edwards, Cherry, additional, Ferguson, Deborah, additional, Allen, Jane, additional, and Almond, Neil, additional

Published
2005
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30. Vaccination with live attenuated simian immunodeficiency virus causes dynamic changes in intestinal CD4+CCR5+ T cells.

Author

Bo Li, Berry, Neil, Ham, Claire, Ferguson, Deborah, Smith, Deborah, Hall, Joanna, Page, Mark, Quartey-Papafio, Ruby, Elsley, William, Robinson, Mark, Almond, Neil, and Stebbings, Richard

Subjects
VACCINATION, T cells, SIMIAN immunodeficiency virus, VIRUS diseases, IMMUNODEFICIENCY
Abstract

Background: Vaccination with live attenuated SIV can protect against detectable infection with wild-type virus. We have investigated whether target cell depletion contributes to the protection observed. Following vaccination with live attenuated SIV the frequency of intestinal CD4+CCR5+ T cells, an early target of wild-type SIV infection and destruction, was determined at days 3, 7, 10, 21 and 125 post inoculation. Results: In naive controls, modest frequencies of intestinal CD4+CCR5+ T cells were predominantly found within the LPL TTrM-1 and IEL TTrM-2 subsets. At day 3, LPL and IEL CD4+CCR5+ TEM cells were dramatically increased whilst less differentiated subsets were greatly reduced, consistent with activation-induced maturation. CCR5 expression remained high at day 7, although there was a shift in subset balance from CD4+CCR5+ TEM to less differentiated TTrM-2 cells. This increase in intestinal CD4+CCR5+ T cells preceded the peak of SIV RNA plasma loads measured at day 10. Greater than 65.9% depletion of intestinal CD4+CCR5+ T cells followed at day 10, but overall CD4+ T cell homeostasis was maintained by increased CD4+CCR5- T cells. At days 21 and 125, high numbers of intestinal CD4+ CCR5- naive TN cells were detected concurrent with greatly increased CD4+CCR5+ LPL TTrM-2 and IEL TEM cells at day 125, yet SIV RNA plasma loads remained low. Conclusions: This increase in intestinal CD4+CCR5+ T cells, following vaccination with live attenuated SIV, does not correlate with target cell depletion as a mechanism of protection. Instead, increased intestinal CD4+CCR5+ T cells may correlate with or contribute to the protection conferred by vaccination with live attenuated SIV. [ABSTRACT FROM AUTHOR]

Published
2011
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32. Antibody Responses after Intravaginal Immunisation with Trimeric HIV-1CN54 clade C gp140 in Carbopol Gel are Augmented by Systemic Priming or Boosting with an Adjuvanted Formulation

Author

Cranage, Martin P., Fraser, Carol A., Cope, Alethea, McKay, Paul F., Cole, Tom, Mahmoud, A. Nasir, Hall, Joanna, Giles, Elaine, Voss, Gerald, Page, Mark, Almond, Neil, Shattock, Robin J., and Seaman, Michael S.

Subjects
immunisation, vagina, HIV-gp140
Abstract

Optimum strategies to elicit and maintain antibodies at mucosal portals of virus entry are critical for the development of vaccines against human immunodeficiency virus (HIV). Here we show in non-human primates that a novel regimen of repeated intravaginal delivery of a non-adjuvanted, soluble recombinant trimeric HIV-1\(_{CN54}\) clade C envelope glycoprotein (gp140) administered in Carbopol gel can prime for B-cell responses even in the absence of seroconversion. Following 3 cycles of repeated intravaginal administration, throughout each intermenses interval, 3 of 4 macaques produced or boosted systemic and mucosally-detected antibodies upon intramuscular immunisation with gp140 formulated in AS01 adjuvant. Reciprocally, a single intramuscular immunisation primed 3 of 4 macaques for antibody boosting after a single cycle of intravaginal immunisation. Virus neutralising activity was detected against clade C and clade B HIV-1 envelopes but was restricted to highly neutralisation sensitive pseudoviruses.

Published
2011
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34. Walk YOURSELF THIN.

Author

Hall, Joanna

Subjects
WALKACTIVE Programme (Book), HALL, Joanna, ATKIN, Lucy
Abstract

An excerpt from the book "Walkactive Programme," by Joanna Hall and Lucy Atkin is presented.

Published
2013

35. Effect of hydrocortisone on mortality and organ support in patients with severe COVID-19

Author

Angus, Derek, Derde, Lennie, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen, Beane, Abigail, van Bentum-Puijk, Wilma, Berry, Lindsay, Bhimani, Zahra, Bonten, Marc, Bradbury, Charlotte, Brunkhorst, Frank, Buxton, Meredith, Buzgau, Adrian, Cheng, Allen, de Jong, Menno, Detry, Michelle, Estcourt, Lise, Fitzgerald, Mark, Goossens, Herman, Green, Cameron, Haniffa, Rashan, Higgins, Alisa, Horvat, Christopher, Hullegie, Sebastiaan, Kruger, Peter, Lamontagne, Francois, Lawler, Patrick, Linstrum, Kelsey, Litton, Edward, Lorenzi, Elizabeth, Marshall, John, Mcauley, Daniel, Mcglothin, Anna, Mcguinness, Shay, Mcverry, Bryan, Montgomery, Stephanie, Mouncey, Paul, Murthy, Srinivas, Nichol, Alistair, Parke, Rachael, Parker, Jane, Rowan, Kathryn, Sanil, Ashish, Santos, Marlene, Saunders, Christina, Seymour, Christopher, Turner, Anne, van de Veerdonk, Frank, Venkatesh, Balasubramanian, Zarychanski, Ryan, Berry, Scott, Lewis, Roger, Mcarthur, Colin, Webb, Steven, Gordon, Anthony, NIHR, Hôpital Raymond Poincaré [AP-HP], Writing Committee for the REMAP-CAP Investigators, Farah Al-Beidh, Derek Angus, Djillali Annane, Yaseen Arabi, Wilma van Bentum-Puijk, Scott Berry, Abigail Beane, Zahra Bhimani, Marc Bonten, Charlotte Bradbury, Frank Brunkhorst, Meredith Buxton, Allen Cheng, Menno De Jong, Lennie Derde, Lise Estcourt, Herman Goossens, Anthony Gordon, Cameron Green, Rashan Haniffa, Francois Lamontagne, Patrick Lawler, Edward Litton, John Marshall, Colin McArthur, Daniel McAuley, Shay McGuinness, Bryan McVerry, Stephanie Montgomery, Paul Mouncey, Srinivas Murthy, Alistair Nichol, Rachael Parke, Kathryn Rowan, Christopher Seymour, Anne Turner, Frank van de Veerdonk, Steve Webb, Ryan Zarychanski, Lewis Campbell, Andrew Forbes, David Gattas, Stephane Heritier, Lisa Higgins, Peter Kruger, Sandra Peake, Jeffrey Presneill, Ian Seppelt, Tony Trapani, Paul Young, Sean Bagshaw, Nick Daneman, Niall Ferguson, Cheryl Misak, Marlene Santos, Sebastiaan Hullegie, Mathias Pletz, Gernot Rohde, Kathy Rowan, Brian Alexander, Kim Basile, Timothy Girard, Christopher Horvat, David Huang, Kelsey Linstrum, Jennifer Vates, Richard Beasley, Robert Fowler, Steve McGloughlin, Susan Morpeth, David Paterson, Bala Venkatesh, Tim Uyeki, Kenneth Baillie, Eamon Duffy, Rob Fowler, Thomas Hills, Katrina Orr, Asad Patanwala, Steve Tong, Mihai Netea, Shilesh Bihari, Marc Carrier, Dean Fergusson, Ewan Goligher, Ghady Haidar, Beverley Hunt, Anand Kumar, Mike Laffan, Patrick Lawless, Sylvain Lother, Peter McCallum, Saskia Middeldopr, Zoe McQuilten, Matthew Neal, John Pasi, Roger Schutgens, Simon Stanworth, Alexis Turgeon, Alexandra Weissman, Neill Adhikari, Matthew Anstey, Emily Brant, Angelique de Man, Francois Lamonagne, Marie-Helene Masse, Andrew Udy, Donald Arnold, Phillipe Begin, Richard Charlewood, Michael Chasse, Mark Coyne, Jamie Cooper, James Daly, Iain Gosbell, Heli Harvala-Simmonds, Tom Hills, Sheila MacLennan, David Menon, John McDyer, Nicole Pridee, David Roberts, Manu Shankar-Hari, Helen Thomas, Alan Tinmouth, Darrell Triulzi, Tim Walsh, Erica Wood, Carolyn Calfee, Cecilia O’Kane, Murali Shyamsundar, Pratik Sinha, Taylor Thompson, Ian Young, Shailesh Bihari, Carol Hodgson, John Laffey, Danny McAuley, Neil Orford, Ary Neto, Michelle Detry, Mark Fitzgerald, Roger Lewis, Anna McGlothlin, Ashish Sanil, Christina Saunders, Lindsay Berry, Elizabeth Lorenzi, Eliza Miller, Vanessa Singh, Claire Zammit, Wilma van Bentum Puijk, Wietske Bouwman, Yara Mangindaan, Lorraine Parker, Svenja Peters, Ilse Rietveld, Kik Raymakers, Radhika Ganpat, Nicole Brillinger, Rene Markgraf, Kate Ainscough, Kathy Brickell, Aisha Anjum, Janis-Best Lane, Alvin Richards-Belle, Michelle Saull, Daisy Wiley, Julian Bion, Jason Connor, Simon Gates, Victoria Manax, Tom van der Poll, John Reynolds, Marloes van Beurden, Evelien Effelaar, Joost Schotsman, Craig Boyd, Cain Harland, Audrey Shearer, Jess Wren, Giles Clermont, William Garrard, Kyle Kalchthaler, Andrew King, Daniel Ricketts, Salim Malakoutis, Oscar Marroquin, Edvin Music, Kevin Quinn, Heidi Cate, Karen Pearson, Joanne Collins, Jane Hanson, Penny Williams, Shane Jackson, Adeeba Asghar, Sarah Dyas, Mihaela Sutu, Sheenagh Murphy, Dawn Williamson, Nhlanhla Mguni, Alison Potter, David Porter, Jayne Goodwin, Clare Rook, Susie Harrison, Hannah Williams, Hilary Campbell, Kaatje Lomme, James Williamson, Jonathan Sheffield, Willian van’t Hoff, Phobe McCracken, Meredith Young, Jasmin Board, Emma Mart, Cameron Knott, Julie Smith, Catherine Boschert, Julia Affleck, Mahesh Ramanan, Ramsy D’Souza, Kelsey Pateman, Arif Shakih, Winston Cheung, Mark Kol, Helen Wong, Asim Shah, Atul Wagh, Joanne Simpson, Graeme Duke, Peter Chan, Brittney Cartner, Stephanie Hunter, Russell Laver, Tapaswi Shrestha, Adrian Regli, Annamaria Pellicano, James McCullough, Mandy Tallott, Nikhil Kumar, Rakshit Panwar, Gail Brinkerhoff, Cassandra Koppen, Federica Cazzola, Matthew Brain, Sarah Mineall, Roy Fischer, Vishwanath Biradar, Natalie Soar, Hayden White, Kristen Estensen, Lynette Morrison, Joanne Smith, Melanie Cooper, Monash Health, Yahya Shehabi, Wisam Al-Bassam, Amanda Hulley, Christina Whitehead, Julie Lowrey, Rebecca Gresha, James Walsham, Jason Meyer, Meg Harward, Ellen Venz, Patricia Williams, Catherine Kurenda, Kirsy Smith, Margaret Smith, Rebecca Garcia, Deborah Barge, Deborah Byrne, Kathleen Byrne, Alana Driscoll, Louise Fortune, Pierre Janin, Elizabeth Yarad, Naomi Hammond, Frances Bass, Angela Ashelford, Sharon Waterson, Steve Wedd, Robert McNamara, Heidi Buhr, Jennifer Coles, Sacha Schweikert, Bradley Wibrow, Rashmi Rauniyar, Erina Myers, Ed Fysh, Ashlish Dawda, Bhaumik Mevavala, Ed Litton, Janet Ferrier, Priya Nair, Hergen Buscher, Claire Reynolds, John Santamaria, Leanne Barbazza, Jennifer Homes, Roger Smith, Lauren Murray, Jane Brailsford, Loretta Forbes, Teena Maguire, Vasanth Mariappa, Judith Smith, Scott Simpson, Matthew Maiden, Allsion Bone, Michelle Horton, Tania Salerno, Martin Sterba, Wenli Geng, Pieter Depuydt, Jan De Waele, Liesbet De Bus, Jan Fierens, Stephanie Bracke, Brenda Reeve, William Dechert, Michaël Chassé, François Martin Carrier, Dounia Boumahni, Fatna Benettaib, Ali Ghamraoui, David Bellemare, Ève Cloutier, Charles Francoeur, François Lamontagne, Frédérick D’Aragon, Elaine Carbonneau, Julie Leblond, Gloria Vazquez-Grande, Nicole Marten, Maggie Wilson, Martin Albert, Karim Serri, Alexandros Cavayas, Mathilde Duplaix, Virginie Williams, Bram Rochwerg, Tim Karachi, Simon Oczkowski, John Centofanti, Tina Millen, Erick Duan, Jennifer Tsang, Lisa Patterson, Shane English, Irene Watpool, Rebecca Porteous, Sydney Miezitis, Lauralyn McIntyre, Laurent Brochard, Karen Burns, Gyan Sandhu, Imrana Khalid, Alexandra Binnie, Elizabeth Powell, Alexandra McMillan, Tracy Luk, Noah Aref, Zdravko Andric, Sabina Cviljevic, Renata Đimoti, Marija Zapalac, Gordan Mirković, Bruno Baršić, Marko Kutleša, Viktor Kotarski, Ana Vujaklija Brajković, Jakša Babel, Helena Sever, Lidija Dragija, Ira Kušan, Suvi Vaara, 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David Shaw, Zudin Puthucheary, Timothy Martin, Filipa Santos, Ruzena Uddin, Alastair Somerville, Kate Colette Tatham, Shaman Jhanji, Ethel Black, Arnold Dela Rosa, Ryan Howle, Redmond Tully, Andrew Drummond, Joy Dearden, Jennifer Philbin, Sheila Munt, Alain Vuylsteke, Charles Chan, Saji Victor, Ramprasad Matsa, Minerva Gellamucho, Ben Creagh-Brown, Joe Tooley, Laura Montague, Fiona De Beaux, Laetitia Bullman, Ian Kersiake, Carrie Demetriou, Sarah Mitchard, Lidia Ramos, Katie White, Phil Donnison, Maggie Johns, Ruth Casey, Lehentha Mattocks, Sarah Salisbury, Paul Dark, Andrew Claxton, Danielle McLachlan, Kathryn Slevin, Stephanie Lee, Jonathan Hulme, Sibet Joseph, Fiona Kinney, Ho Jan Senya, Aneta Oborska, Abdul Kayani, Bernard Hadebe, Rajalakshmi Orath Prabakaran, Lesley Nichols, Matt Thomas, Ruth Worner, Beverley Faulkner, Emma Gendall, Kati Hayes, Colin Hamilton-Davies, Carmen Chan, Celina Mfuko, Hakam Abbass, Vineela Mandadapu, Susannah Leaver, Daniel Forton, Kamal Patel, Elankumaran Paramasivam, Matthew Powell, Richard Gould, Elizabeth Wilby, Clare Howcroft, Dorota Banach, Ziortza Fernández de Pinedo Artaraz, Leilani Cabreros, Ian White, Maria Croft, Nicky Holland, Rita Pereira, Ahmed Zaki, David Johnson, Matthew Jackson, Hywel Garrard, Vera Juhaz, Alistair Roy, Anthony Rostron, Lindsey Woods, Sarah Cornell, Suresh Pillai, Rachel Harford, Tabitha Rees, Helen Ivatt, Ajay Sundara Raman, Miriam Davey, Kelvin Lee, Russell Barber, Manish Chablani, Farooq Brohi, Vijay Jagannathan, Michele Clark, Sarah Purvis, Bill Wetherill, Ahilanandan Dushianthan, Rebecca Cusack, Kim de Courcy-Golder, Simon Smith, Susan Jackson, Ben Attwood, Penny Parsons, Valerie Page, Xiao Bei Zhao, Deepali Oza, Jonathan Rhodes, Tom Anderson, Sheila Morris, Charlotte Xia Le Tai, Amy Thomas, Alexandra Keen, Stephen Digby, Nicholas Cowley, Laura Wild, David Southern, Harsha Reddy, Andy Campbell, Claire Watkins, Sara Smuts, Omar Touma, Nicky Barnes, Peter Alexander, Tim Felton, Susan Ferguson, Katharine Sellers, Joanne Bradley-Potts, David Yates, Isobel Birkinshaw, Kay Kell, Nicola Marshall, Lisa Carr-Knott, Charlotte Summers, and Mégarbane, Bruno

Subjects
[SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, General Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Writing Committee for the REMAP-CAP Investigators, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.TOX] Life Sciences [q-bio]/Toxicology, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.TOX]Life Sciences [q-bio]/Toxicology, General & Internal Medicine, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 11 Medical and Health Sciences
Abstract

Importance Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures The primary end point was organ support–free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned –1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support–free days were 0 (IQR, –1 to 15), 0 (IQR, –1 to 13), and 0 (–1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support–free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support–free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions.

Published
2020

36. CD8+ Lymphocytes Do Not Mediate Protection against Acute Superinfection 20 Days after Vaccination with a Live Attenuated Simian Immunodeficiency Virus.

Author

Stebbings, Richard, Berry, Neil, Waldmann, Herman, Bird, Pru, Hale, Geoff, Stott, Jim, North, David, Hull, Robin, Hall, Joanna, Lines, Jenny, Brown, Stuart, D'Arcy, Nikki, Davis, Leanne, Elsley, William, Edwards, Cherry, Ferguson, Deborah, Allen, Jane, and Almond, Neil

Subjects
*T cells, *LYMPHOCYTES, *SIMIAN viruses, *MONOCLONAL antibodies, *VIROLOGY
Abstract

In order to test the hypothesis that CD8+ cytotoxic T lymphocytes mediate protection against acute superinfection, we depleted >99% of CD8+ lymphocytes in live attenuated simian immunodeficiency virus macC8 (SIVmacC8) vaccinees from the onset of vaccination, maintained that depletion for 20 days, and then challenged with pathogenic, wild-type SIVmacJ5. Vaccinees received 5 mg per kg of humanized anti-CD8 monoclonal antibody (MAb) 1 h before inoculation, followed by the same dose again on days 3, 7, 10, 13, and 17. On day 13, peripheral CD8 + T lymphocytes were >99% depleted in three out of four anti-CD8 MAb-treated vaccinees. At this time attenuated SIVmacC8 viral RNA loads in anti-CD8 MAb-treated vaccinees were significantly higher than control vaccinees treated contemporaneously with nonspecific human immunoglobulin. Lymphoid tissue CD8+ T lymphocyte depletion was >99% in three out of four anti-CD8 MAb-treated vaccinees on the day of wild-type SIVmacJ5 challenge. All four control vaccinees and three out of four anti-CD8 MAb-treated vaccinees were protected against detectable superinfection with wild-type SIVmacJ5. Although superinfection with wild-type SIVmacJ5 was detected at postmortem in a single anti-CD8 MAb-treated vaccinee, this did not correlate with the degree of preceding CD8+ T lymphocyte depletion. Clearance of attenuated SIVmacC8 viremia coincided with recovery of normal CD8+ T lymphocyte counts between days 48 and 76. These results support the view that cytotoxic T lymphocytes are important for host-mediated control of SIV primary viremia but do not indicate a central role in protection against acute superinfection conferred by inoculation with live attenuated SIV. [ABSTRACT FROM AUTHOR]

Published
2005
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37. CD8+ lymphocytes do not mediate protection against acute superinfection 20 days after vaccination with a live attenuated simian immunodeficiency virus.

Author

Stebbings R, Berry N, Waldmann H, Bird P, Hale G, Stott J, North D, Hull R, Hall J, Lines J, Brown S, D'Arcy N, Davis L, Elsley W, Edwards C, Ferguson D, Allen J, and Almond N

Subjects
Animals, Lymphocyte Count, Lymphocyte Depletion, Macaca fascicularis, RNA, Viral blood, SAIDS Vaccines administration & dosage, Simian Acquired Immunodeficiency Syndrome prevention & control, Simian Acquired Immunodeficiency Syndrome virology, Superinfection prevention & control, Time Factors, Vaccines, Attenuated administration & dosage, Viral Load, Viremia, Antibodies, Viral blood, CD8-Positive T-Lymphocytes immunology, SAIDS Vaccines immunology, Simian Acquired Immunodeficiency Syndrome immunology, Simian Immunodeficiency Virus immunology, Superinfection immunology, Vaccines, Attenuated immunology
Abstract

In order to test the hypothesis that CD8+ cytotoxic T lymphocytes mediate protection against acute superinfection, we depleted >99% of CD8+ lymphocytes in live attenuated simian immunodeficiency virus macC8 (SIVmacC8) vaccinees from the onset of vaccination, maintained that depletion for 20 days, and then challenged with pathogenic, wild-type SIVmacJ5. Vaccinees received 5 mg per kg of humanized anti-CD8 monoclonal antibody (MAb) 1 h before inoculation, followed by the same dose again on days 3, 7, 10, 13, and 17. On day 13, peripheral CD8+ T lymphocytes were >99% depleted in three out of four anti-CD8 MAb-treated vaccinees. At this time attenuated SIVmacC8 viral RNA loads in anti-CD8 MAb-treated vaccinees were significantly higher than control vaccinees treated contemporaneously with nonspecific human immunoglobulin. Lymphoid tissue CD8+ T lymphocyte depletion was >99% in three out of four anti-CD8 MAb-treated vaccinees on the day of wild-type SIVmacJ5 challenge. All four control vaccinees and three out of four anti-CD8 MAb-treated vaccinees were protected against detectable superinfection with wild-type SIVmacJ5. Although superinfection with wild-type SIVmacJ5 was detected at postmortem in a single anti-CD8 MAb-treated vaccinee, this did not correlate with the degree of preceding CD8+ T lymphocyte depletion. Clearance of attenuated SIVmacC8 viremia coincided with recovery of normal CD8+ T lymphocyte counts between days 48 and 76. These results support the view that cytotoxic T lymphocytes are important for host-mediated control of SIV primary viremia but do not indicate a central role in protection against acute superinfection conferred by inoculation with live attenuated SIV.

Published
2005
Full Text
View/download PDF

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