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2. Natural killer cell responses during SARS-CoV-2 infection and vaccination in people living with HIV-1

Author

Alrubayyi, Aljawharah, Touizer, Emma, Hameiri-Bowen, Dan, Charlton, Bethany, Gea-Mallorquí, Ester, Hussain, Noshin, da Costa, Kelly A. S., Ford, Rosemarie, Rees-Spear, Chloe, Fox, Thomas A., Williams, Ian, Waters, Laura, Barber, Tristan J., Burns, Fiona, Kinloch, Sabine, Morris, Emma, Rowland-Jones, Sarah, McCoy, Laura E., and Peppa, Dimitra

Published
2023
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4. Attenuated humoral responses in HIV after SARS-CoV-2 vaccination linked to B cell defects and altered immune profiles

Author

Touizer, Emma, Alrubayyi, Aljawharah, Ford, Rosemarie, Hussain, Noshin, Gerber, Pehuén Pereyra, Shum, Hiu-Long, Rees-Spear, Chloe, Muir, Luke, Gea-Mallorquí, Ester, Kopycinski, Jakub, Jankovic, Dylan, Jeffery-Smith, Anna, Pinder, Christopher L., Fox, Thomas A., Williams, Ian, Mullender, Claire, Maan, Irfaan, Waters, Laura, Johnson, Margaret, Madge, Sara, Youle, Michael, Barber, Tristan J., Burns, Fiona, Kinloch, Sabine, Rowland-Jones, Sarah, Gilson, Richard, Matheson, Nicholas J., Morris, Emma, Peppa, Dimitra, and McCoy, Laura E.

Published
2023
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9. Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV

Author

Alrubayyi, Aljawharah, Gea-Mallorquí, Ester, Touizer, Emma, Hameiri-Bowen, Dan, Kopycinski, Jakub, Charlton, Bethany, Fisher-Pearson, Natasha, Muir, Luke, Rosa, Annachiara, Roustan, Chloe, Earl, Christopher, Cherepanov, Peter, Pellegrino, Pierre, Waters, Laura, Burns, Fiona, Kinloch, Sabine, Dong, Tao, Dorrell, Lucy, Rowland-Jones, Sarah, McCoy, Laura E., and Peppa, Dimitra

Published
2021
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11. Mapping the human DC lineage through the integration of high-dimensional techniques

Author

Dutertre, Charles-Antoine, See, Peter, Chen, Jinmiao, Günther, Patrick, McGovern, Naomi, Irac, Sergio Erdal, Gunawan, Merry, Beyer, Marc, Händler, Kristian, Duan, Kaibo, Sumatoh, Hermi Rizal Bin, Ruffin, Nicolas, Jouve, Mabel, Gea-Mallorquí, Ester, Hennekam, Raoul C. M., Lim, Tony, Yip, Chan Chung, Wen, Ming, Malleret, Benoit, Low, Ivy, Shadan, Nurhidaya Binte, Fen, Charlene Foong Shu, Tay, Alicia, Lum, Josephine, Zolezzi, Francesca, Larbi, Anis, Poidinger, Michael, Chan, Jerry K. Y., Chen, Qingfeng, Rénia, Laurent, Haniffa, Muzlifah, Benaroch, Philippe, Schlitzer, Andreas, Schultze, Joachim L., Newell, Evan W., and Ginhoux, Florent

Published
2017

12. The Preprint Club

Author

Richter, Felix Clemens, primary, Gea‐Mallorquí, Ester, additional, Mortha, Arthur, additional, Ruffin, Nicolas, additional, and Vabret, Nicolas, additional

Published
2023
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13. Intracellular trafficking of HLA-E and its regulation

Author

He, Wanlin, primary, Gea-Mallorquí, Ester, additional, Colin-York, Huw, additional, Fritzsche, Marco, additional, Gillespie, Geraldine M., additional, Brackenridge, Simon, additional, Borrow, Persephone, additional, and McMichael, Andrew J., additional

Published
2023
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22. Attenuated humoral responses in HIV infection after SARS-CoV-2 vaccination are linked to global B cell defects and cellular immune profiles

Author

Touizer, Emma, primary, Alrubbayi, Aljawharah, additional, Ford, Rosemarie, additional, Hussain, Noshin, additional, Gerber, Pehuén Pereyra, additional, Shum, Hiu-Long, additional, Rees-Spear, Chloe, additional, Muir, Luke, additional, Gea-Mallorquí, Ester, additional, Kopycinski, Jakub, additional, Jankovic, Dylan, additional, Pinder, Christopher, additional, Fox, Thomas A, additional, Williams, Ian, additional, Mullender, Claire, additional, Maan, Irfaan, additional, Waters, Laura, additional, Johnson, Margaret, additional, Madge, Sara, additional, Youle, Michael, additional, Barber, Tristan, additional, Burns, Fiona, additional, Kinloch, Sabine, additional, Rowland-Jones, Sarah, additional, Gilson, Richard, additional, Matheson, Nicholas J, additional, Morris, Emma, additional, Peppa, Dimitra, additional, and McCoy, Laura E, additional

Published
2022
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25. Clonotypic architecture of a Gag‐specific CD8+ T‐cell response in chronic human HIV‐2 infection

Author

Moysi, Eirini, primary, Darko, Samuel, additional, Gea‐Mallorquí, Ester, additional, Petrovas, Constantinos, additional, Almeida, Jorge R., additional, Wolinsky, David, additional, Peng, Yanchun, additional, Jaye, Assan, additional, Stewart‐Jones, Guillaume, additional, Douek, Daniel C., additional, Koup, Richard A., additional, Dong, Tao, additional, and Rowland‐Jones, Sarah, additional

Published
2021
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26. The role and uses of antibodies in COVID-19 infections: a living review

Author

Scourfield, D Oliver, Reed, Sophie G, Quastel, Max, Alderson, Jennifer, Bart, Valentina M T, Teijeira Crespo, Alicia, Jones, Ruth, Pring, Ellie, Richter, Felix Clemens, Ahern, David J, Almuttaqi, Hannah, Alonzi, Dominic S, Alrubayyi, Aljawharah, Alsaleh, Ghada, Batchelor, Vicky, Bayliss, Rebecca, Berthold, Dorothée L, Bezbradica, Jelena S, Bharuchq, Tehmina, Borrmann, Helene, Borsa, Mariana, Borst, Rowie, Brun, Juliane, Burnell, Stephanie E A, Capitani, Lorenzo, Cavounidis, Athena, Chapman, Lucy, Chauveau, Anne, Cifuentes, Liliana, Codd, Amy Susan, Compeer, Ewoud Bernardus, Coveney, Clarissa, Cross, Amy, Danielli, Sara, Davies, Luke C, Dendrou, Calliope A, Dimonte, Sandra, Peter Durairaj, Ruban Rex, Dustin, Lynn B, Dyer, Arthur, Fielding, Ceri, Fischer, Fabian, Gallimore, Awen, Galloway, Sarah, Gammage, Anís, Gea-Mallorquí, Ester, Godkin, Andrew, Hanna, Stephanie Jean, Heuberger, Cornelia, Hulin-Curtis, Sarah, Issa, Fadi, Jones, Emma, Ladell, Kristin, Lauder, Sarah N, Liddiard, Kate, Ligoxygakis, Petros, Lu, Fangfang, MacLachlan, Bruce, Maleki-Toyserkani, Shayda, Mann, Elizabeth H, Marzeda, Anna M, James Matthews, Reginald, Mazet, Julie M, Milicic, Anita, Mitchell, Emma, Moon, Owen, Nguyen, Van Dien, OHanlon, Miriam, Eléonore Pavillet, Clara, Peppa, Dimitra, Pires, Ana, Pring, Eleanor, Reed, Sophie, Rehwinkel, Jan, Richmond, Niamh, Robinson, Alice J B, Rodrigues, Patrícia R S, Sabberwal, Pragati, Sami, Arvind, Peres, Raphael Sanches, Sattentau, Quentin, Schonfeldova, Barbora, Scourfield, David Oliver, Selvakumar, Tharini A, Shepherd, Freya R, Shorten, Cariad, Simon, Anna Katharina, Smith, Adrian L, Crespo, Alicia Teijeira, Tellier, Michael, Thornton, Emily, Uhl, Lion F K, van Grinsven, Erinke, Wann, Angus K T, Williams, Richard, Wilson, Joseph D, Zhou, Dingxi, Zhu, Zihan, and Consortium, Oxford-Cardiff COVID-19 Literature

Subjects
0301 basic medicine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Review Article, Disease, 03 medical and health sciences, 0302 clinical medicine, Immunity, Pandemic, antibodies, Medicine, Infection control, biology, SARS-CoV-2, business.industry, COVID-19, General Medicine, vaccines, nanobodies, 030104 developmental biology, convalescent plasma, Immunology, biology.protein, AcademicSubjects/SCI00960, Antibody, business, long-term immunity, 030217 neurology & neurosurgery
Abstract

Coronavirus disease 2019 has generated a rapidly evolving field of research, with the global scientific community striving for solutions to the current pandemic. Characterizing humoral responses towards SARS-CoV-2, as well as closely related strains, will help determine whether antibodies are central to infection control, and aid the design of therapeutics and vaccine candidates. This review outlines the major aspects of SARS-CoV-2-specific antibody research to date, with a focus on the various prophylactic and therapeutic uses of antibodies to alleviate disease in addition to the potential of cross-reactive therapies and the implications of long-term immunity.

Published
2021

27. Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV

Author

Alrubayyi, Aljawharah, primary, Gea-Mallorquí, Ester, additional, Touizer, Emma, additional, Hameiri-Bowen, Dan, additional, Kopycinski, Jakub, additional, Charlton, Bethany, additional, Fisher-Pearson, Natasha, additional, Muir, Luke, additional, Rosa, Annachiara, additional, Roustan, Chloë, additional, Earl, Christopher, additional, Cherepanov, Peter, additional, Pellegrino, Pierre, additional, Waters, Laura, additional, Burns, Fiona, additional, Kinloch, Sabine, additional, Dong, Tao, additional, Dorrell, Lucy, additional, Rowland-Jones, Sarah, additional, McCoy, Laura, additional, and Peppa, Dimitra, additional

Published
2021
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28. Mucosal immune responses in COVID19 - a living review

Author

Pearson, Claire F, Jeffery, Rebecca, Ahern, David J, Almuttaqi, Hannah, Alonzi, Dominic S, Alrubayyi, Aljawharah, Alsaleh, Ghada, Bart, Valentina M T, Batchelor, Vicky, Bayliss, Rebecca, Berthold, Dorothée L, Bezbradica, Jelena S, Bharuchq, Tehmina, Borrmann, Helene, Borsa, Mariana, Borst, Rowie, Brun, Juliane, Burnell, Stephanie, Capitani, Lorenzo, Cavounidis, Athena, Chapman, Lucy, Chauveau, Anne, Cifuentes, Liliana, Codd, Amy Susan, Compeer, Ewoud Bernardus, Coveney, Clarissa, Cross, Amy, Danielli, Sara, Davies, Luke C, Dendrou, Calliope A, Dimonte, Sandra, Peter Durairaj, Ruban Rex, Dustin, Lynn B, Dyer, Arthur, Fielding, Ceri, Fischer, Fabian, Gallimore, Awen, Galloway, Sarah, Gammage, Anís, Gea-Mallorquí, Ester, Godkin, Andrew, Hanna, Stephanie Jean, Heuberger, Cornelia, Hulin-Curtis, Sarah, Issa, Fadi, Jones, Emma, Jones, Ruth, Ladell, Kristin, Lauder, Sarah N, Liddiard, Kate, Ligoxygakis, Petros, Lu, Fangfang, MacLachlan, Bruce, Maleki-Toyserkani, Shayda, Mann, Elizabeth H, Marzeda, Anna M, Matthews, Reginald James, Mazet, Julie M, Milicic, Anita, Mitchell, Emma, Moon, Owen, Nguyen, Van Dien, OHanlon, Miriam, Pavillet, Clara Eléonore, Peppa, Dimitra, Pires, Ana, Pring, Eleanor, Quastel, Max, Reed, Sophie, Rehwinkel, Jan, Richmond, Niamh, Richter, Felix Clemens, Robinson, Alice J B, Rodrigues, Patrícia R S, Sabberwal, Pragati, Sami, Arvind, Peres, Raphael Sanches, Sattentau, Quentin, Schonfeldova, Barbora, Scourfield, David Oliver, Selvakumar, Tharini A, Shepherd, Freya R, Shorten, Cariad, Simon, Anna Katharina, Smith, Adrian L, Crespo, Alicia Teijeira, Tellier, Michael, Thornton, Emily, Uhl, Lion F K, van Grinsven, Erinke, Wann, Angus K T, Williams, Richard, Wilson, Joseph D, Zhou, Dingxi, Zhu, Zihan, and Thornton, Emily E

Subjects
0301 basic medicine, Gastrointestinal tract, Mucosal Immune Responses, Lung, Coronavirus disease 2019 (COVID-19), business.industry, Short Communication, COVID-19, microbiome, General Medicine, Disease, Virus, lung, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Immune system, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunology, medicine, mucosal immunity, gut, Microbiome, business
Abstract

COVID-19 was initially characterized as a disease primarily of the lungs, but it is becoming increasingly clear that the SARS-CoV2 virus is able to infect many organs and cause a broad pathological response. The primary infection site is likely to be a mucosal surface, mainly the lungs or the intestine, where epithelial cells can be infected with virus. Although it is clear that virus within the lungs can cause severe pathology, driven by an exaggerated immune response, infection within the intestine generally seems to cause minor or no symptoms. In this review, we compare the disease processes between the lungs and gastrointestinal tract, and what might drive these different responses. As the microbiome is a key part of mucosal barrier sites, we also consider the effect that microbial species may play on infection and the subsequent immune responses. Because of difficulties obtaining tissue samples, there are currently few studies focused on the local mucosal response rather than the systemic response, but understanding the local immune response will become increasingly important for understanding the mechanisms of disease in order to develop better treatments.

Published
2020

29. T cell phenotypes in COVID-19 - a living review

Author

Hanna, Stephanie J, Codd, Amy S, Gea-Mallorqui, Ester, Scourfield, D Oliver, Richter, Felix C, Ladell, Kristin, Borsa, Mariana, Compeer, Ewoud B, Moon, Owen R, Galloway, Sarah A E, Dimonte, Sandra, Capitani, Lorenzo, Shepherd, Freya R, Wilson, Joseph D, Uhl, Lion F K, Ahern, David J, Almuttaqi, Hannah, Alonzi, Dominic S, Alrubayyi, Aljawharah, Alsaleh, Ghada, Bart, Valentina M T, Batchelor, Vicky, Bayliss, Rebecca, Berthold, Dorothée L, Bezbradica, Jelena S, Bharuchq, Tehmina, Borrmann, Helene, Borst, Rowie, Brun, Juliane, Burnell, Stephanie, Cavounidis, Athena, Chapman, Lucy, Chauveau, Anne, Cifuentes, Liliana, Codd, Amy Susan, Compeer, Ewoud Bernardus, Coveney, Clarissa, Cross, Amy, Danielli, Sara, Davies, Luke C, Dendrou, Calliope A, Peter Durairaj, Ruban Rex, Dustin, Lynn B, Dyer, Arthur, Fielding, Ceri, Fischer, Fabian, Gallimore, Awen, Galloway, Sarah, Gammage, Anís, Gea-Mallorquí, Ester, Godkin, Andrew, Heuberger, Cornelia, Hulin-Curtis, Sarah, Issa, Fadi, Jones, Emma, Jones, Ruth, Lauder, Sarah N, Liddiard, Kate, Ligoxygakis, Petros, Lu, Fangfang, MacLachlan, Bruce, Maleki-Toyserkani, Shayda, Mann, Elizabeth H, Marzeda, Anna M, Matthews, Reginald James, Mazet, Julie M, Milicic, Anita, Mitchell, Emma, Moon, Owen, Nguyen, Van Dien, OHanlon, Miriam, Eléonore Pavillet, Clara, Peppa, Dimitra, Pires, Ana, Pring, Eleanor, Quastel, Max, Reed, Sophie, Rehwinkel, Jan, Richmond, Niamh, Richter, Felix Clemens, Robinson, Alice J B, Rodrigues, Patrícia R S, Sabberwal, Pragati, Sami, Arvind, Peres, Raphael Sanches, Sattentau, Quentin, Schonfeldova, Barbora, Scourfield, David Oliver, Selvakumar, Tharini A, Shorten, Cariad, Simon, Anna Katharina, Smith, Adrian L, Crespo, Alicia Teijeira, Tellier, Michael, Thornton, Emily, van Grinsven, Erinke, Wann, Angus K T, Williams, Richard, Zhou, Dingxi, Zhu, Zihan, Gallimore, Awen M, and Consortium, Oxford-Cardiff COVID-19 Literature

Subjects
0301 basic medicine, T cell, Short Communication, T cells, Biology, phenotypes, COVID-19, antigen-specific, peripheral blood, lung, Virus, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, Lung, Mechanism (biology), General Medicine, Acquired immune system, Phenotype, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunology, AcademicSubjects/SCI00960, Function (biology)
Abstract

COVID-19 is characterized by profound lymphopenia in the peripheral blood, and the remaining T cells display altered phenotypes, characterized by a spectrum of activation and exhaustion. However, antigen-specific T cell responses are emerging as a crucial mechanism for both clearance of the virus and as the most likely route to long-lasting immune memory that would protect against re-infection. Therefore, T cell responses are also of considerable interest in vaccine development. Furthermore, persistent alterations in T cell subset composition and function post-infection have important implications for patients’ long-term immune function. In this review, we examine T cell phenotypes, including those of innate T cells, in both peripheral blood and lungs, and consider how key markers of activation and exhaustion correlate with, and may be able to predict, disease severity. We focus on SARS-CoV-2-specific T cells to elucidate markers that may indicate formation of antigen-specific T cell memory. We also examine peripheral T cell phenotypes in recovery and the likelihood of long-lasting immune disruption. Finally, we discuss T cell phenotypes in the lung as important drivers of both virus clearance and tissue damage. As our knowledge of the adaptive immune response to COVID-19 rapidly evolves, it has become clear that while some areas of the T cell response have been investigated in some detail, others, such as the T cell response in children remain largely unexplored. Therefore, this review will also highlight areas where T cell phenotypes require urgent characterisation.

Published
2020

33. Innate immunology in COVID-19—a living review. Part II: dysregulated inflammation drives immunopathology

Author

Rodrigues, Patrícia R S, primary, Alrubayyi, Aljawharah, additional, Pring, Ellie, additional, Bart, Valentina M T, additional, Jones, Ruth, additional, Coveney, Clarissa, additional, Lu, Fangfang, additional, Tellier, Michael, additional, Maleki-Toyserkani, Shayda, additional, Richter, Felix C, additional, Scourfield, D Oliver, additional, Gea-Mallorquí, Ester, additional, and Davies, Luke C, additional

Published
2020
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35. Neutrophilia, lymphopenia and myeloid dysfunction: a living review of the quantitative changes to innate and adaptive immune cells which define COVID-19 pathology.

Author

Codd, Amy S, Hanna, Stephanie J, Compeer, Ewoud B, Richter, Felix C, Pring, Eleanor J, Gea-Mallorquí, Ester, Borsa, Mariana, Moon, Owen R, Scourfield, D Oliver, Oxford-Cardiff COVID-19 Literature Consortium, Ahern, David J, Almuttaqi, Hannah, Alonzi, Dominic S, Alrubayyi, Aljawharah, Alsaleh, Ghada, Bart, Valentina M T, Batchelor, Vicky, Bayliss, Rebecca, Berthold, Dorothée L, and Bezbradica, Jelena S

Subjects
SARS-CoV-2, COVID-19, LYMPHOPENIA
Abstract

Destabilization of balanced immune cell numbers and frequencies is a common feature of viral infections. This occurs due to, and further enhances, viral immune evasion and survival. Since the discovery of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), which manifests in coronavirus disease 2019 (COVID-19), a great number of studies have described the association between this virus and pathologically increased or decreased immune cell counts. In this review, we consider the absolute and relative changes to innate and adaptive immune cell numbers, in COVID-19. In severe disease particularly, neutrophils are increased, which can lead to inflammation and tissue damage. Dysregulation of other granulocytes, basophils and eosinophils represents an unusual COVID-19 phenomenon. Contrastingly, the impact on the different types of monocytes leans more strongly to an altered phenotype, e.g. HLA-DR expression, rather than numerical changes. However, it is the adaptive immune response that bears the most profound impact of SARS-CoV-2 infection. T cell lymphopenia correlates with increased risk of intensive care unit admission and death; therefore, this parameter is particularly important for clinical decision-making. Mild and severe diseases differ in the rate of immune cell counts returning to normal levels post disease. Tracking the recovery trajectories of various immune cell counts may also have implications for long-term COVID-19 monitoring. This review represents a snapshot of our current knowledge, showing that much has been achieved in a short period of time. Alterations in counts of distinct immune cells represent an accessible metric to inform patient care decisions or predict disease outcomes. [ABSTRACT FROM AUTHOR]

Published
2021
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36. Innate immunology in COVID-19--a living review. Part I: viral entry, sensing and evasion.

Author

Coveney, Clarissa, Tellier, Michel, Fangfang Lu, Maleki-Toyserkani, Shayda, Jones, Ruth, Bart, Valentina M. T., Pring, Ellie, Alrubayyi, Aljawharah, Richter, Felix C., Scourfield, D. Oliver, Rehwinkel, Jan, Rodrigues, Patrícia R. S., Davies, Luke C., and Gea-Mallorquí, Ester

Subjects
COVID-19, SARS-CoV-2, INTERFERONS, VACCINES, VIRUSES
Abstract

The coronavirus infectious disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a world health concern and can cause severe disease and high mortality in susceptible groups. While vaccines offer a chance to treat disease, prophylactic and anti-viral treatments are still of vital importance, especially in context of the mutative ability of this group of viruses. Therefore, it is essential to elucidate the molecular mechanisms of viral entry, innate sensing and immune evasion of SARS-CoV-2, which control the triggers of the subsequent excessive in- flammatory response. Viral evasion strategies directly target anti-viral immunity, counteracting host restriction factors and hijacking signalling pathways to interfere with interferon production. In Part I of this review, we examine SARS-CoV-2 viral entry and the described immune evasion mechanisms to provide a perspective on how the failure in initial viral sensing by infected cells can lead to immune dysregulation causing fatal COVID-19, discussed in Part II. [ABSTRACT FROM AUTHOR]

Published
2020
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37. Mapping the human DC lineage through the integration of high-dimensional techniques

Author

See, Peter, primary, Dutertre, Charles-Antoine, additional, Chen, Jinmiao, additional, Günther, Patrick, additional, McGovern, Naomi, additional, Irac, Sergio Erdal, additional, Gunawan, Merry, additional, Beyer, Marc, additional, Händler, Kristian, additional, Duan, Kaibo, additional, Sumatoh, Hermi Rizal Bin, additional, Ruffin, Nicolas, additional, Jouve, Mabel, additional, Gea-Mallorquí, Ester, additional, Hennekam, Raoul C. M., additional, Lim, Tony, additional, Yip, Chan Chung, additional, Wen, Ming, additional, Malleret, Benoit, additional, Low, Ivy, additional, Shadan, Nurhidaya Binte, additional, Fen, Charlene Foong Shu, additional, Tay, Alicia, additional, Lum, Josephine, additional, Zolezzi, Francesca, additional, Larbi, Anis, additional, Poidinger, Michael, additional, Chan, Jerry K. Y., additional, Chen, Qingfeng, additional, Rénia, Laurent, additional, Haniffa, Muzlifah, additional, Benaroch, Philippe, additional, Schlitzer, Andreas, additional, Schultze, Joachim L., additional, Newell, Evan W., additional, and Ginhoux, Florent, additional

Published
2017
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40. Mapping the human DC lineage through the integration of high-dimensional techniques

Author

See, Peter, Dutertre, Charles-Antoine, Chen, Jinmiao, Günther, Patrick, McGovern, Naomi, Irac, Sergio Erdal, Gunawan, Merry, Beyer, Marc, Händler, Kristian, Duan, Kaibo, Sumatoh, Hermi Rizal Bin, Ruffin, Nicolas, Jouve, Mabel, Gea-Mallorquí, Ester, Hennekam, Raoul CM, Lim, Tony, Yip, Chan Chung, Wen, Ming, Malleret, Benoit, Low, Ivy, Shadan, Nurhidaya Binte, Fen, Charlene Foong Shu, Tay, Alicia, Lum, Josephine, Zolezzi, Francesca, Larbi, Anis, Poidinger, Michael, Chan, Jerry KY, Chen, Qingfeng, Rénia, Laurent, Haniffa, Muzlifah, Benaroch, Philippe, Schlitzer, Andreas, Schultze, Joachim L, Newell, Evan W, and Ginhoux, Florent

Subjects
Blood Cells, Sequence Analysis, RNA, Humans, Cell Differentiation, Cell Lineage, Dendritic Cells, Cell Separation, Single-Cell Analysis, 3. Good health, Unsupervised Machine Learning

42. Attenuated humoral responses in HIV infection after SARS-CoV-2 vaccination are linked to global B cell defects and cellular immune profiles.

Author

Touizer E, Alrubbayi A, Ford R, Hussain N, Gerber PP, Shum HL, Rees-Spear C, Muir L, Gea-Mallorquí E, Kopycinski J, Jankovic D, Pinder C, Fox TA, Williams I, Mullender C, Maan I, Waters L, Johnson M, Madge S, Youle M, Barber T, Burns F, Kinloch S, Rowland-Jones S, Gilson R, Matheson NJ, Morris E, Peppa D, and McCoy LE

Abstract

People living with HIV (PLWH) on suppressive antiretroviral therapy (ART) can have residual immune dysfunction and often display poorer responses to vaccination. We assessed in a cohort of PLWH (n=110) and HIV negative controls (n=64) the humoral and spike-specific B-cell responses following 1, 2 or 3 SARS-CoV-2 vaccine doses. PLWH had significantly lower neutralizing antibody (nAb) titers than HIV-negative controls at all studied timepoints. Moreover, their neutralization breadth was reduced with fewer individuals developing a neutralizing response against the Omicron variant (BA.1) relative to controls. We also observed a delayed development of neutralization in PLWH that was underpinned by a reduced frequency of spike-specific memory B cells (MBCs) and pronounced B cell dysfunction. Improved neutralization breadth was seen after the third vaccine dose in PLWH but lower nAb responses persisted and were associated with global, but not spike-specific, MBC dysfunction. In contrast to the inferior antibody responses, SARS-CoV-2 vaccination induced robust T cell responses that cross-recognized variants in PLWH. Strikingly, a subset of PLWH with low or absent neutralization had detectable functional T cell responses. These individuals had reduced numbers of circulating T follicular helper cells and an enriched population of CXCR3 + CD127 + CD8 + T cells after two doses of SARS-CoV-2 vaccination, which may compensate for sub-optimal serological responses in the event of infection. Therefore, normalisation of B cell homeostasis could improve serological responses to vaccines in PLWH and evaluating T cell immunity could provide a more comprehensive immune status profile in these individuals and others with B cell imbalances.

Published
2022
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43. Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV.

Author

Alrubayyi A, Gea-Mallorquí E, Touizer E, Hameiri-Bowen D, Kopycinski J, Charlton B, Fisher-Pearson N, Muir L, Rosa A, Roustan C, Earl C, Cherepanov P, Pellegrino P, Waters L, Burns F, Kinloch S, Dong T, Dorrell L, Rowland-Jones S, McCoy LE, and Peppa D

Abstract

There is an urgent need to understand the nature of immune responses against SARS-CoV-2, to inform risk-mitigation strategies for people living with HIV (PLWH). We show that the majority of PLWH, controlled on ART, mount a functional adaptive immune response to SARS-CoV-2. Humoral and SARS-CoV-2-specific T cell responses are comparable between HIV-positive and negative subjects and persist 5-7 months following predominately mild COVID-19 disease. T cell responses against Spike, Membrane and Nucleocapsid are the most prominent, with SARS-CoV-2-specific CD4 T cells outnumbering CD8 T cells. We further show that the overall magnitude of SARS-CoV-2-specific T cell responses relates to the size of the naive CD4 T cell pool and the CD4:CD8 ratio in PLWH, in whom disparate antibody and T cell responses are observed. These findings suggest that inadequate immune reconstitution on ART, could hinder immune responses to SARS-CoV-2 with implications for the individual management and vaccine effectiveness in PLWH.

Published
2021
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44. Engineering new mycobacterial vaccine design for HIV-TB pediatric vaccine vectored by lysine auxotroph of BCG.

Author

Saubi N, Gea-Mallorquí E, Ferrer P, Hurtado C, Sánchez-Úbeda S, Eto Y, Gatell JM, Hanke T, and Joseph J

Abstract

In this study, we have engineered a new mycobacterial vaccine design by using an antibiotic-free plasmid selection system. We assembled a novel Escherichia coli (E. coli)-mycobacterial shuttle plasmid p2auxo.HIVA, expressing the HIV-1 clade A immunogen HIVA. This shuttle vector employs an antibiotic resistance-free mechanism for plasmid selection and maintenance based on glycine complementation in E. coli and lysine complementation in mycobacteria. This plasmid was first transformed into glycine auxotroph of E. coli strain and subsequently transformed into lysine auxotroph of Mycobacterium bovis BCG strain to generate vaccine BCG.HIVA(2auxo). We demonstrated that the episomal plasmid p2auxo.HIVA was stable in vivo over a 7-week period and genetically and phenotypically characterized the BCG.HIVA(2auxo) vaccine strain. The BCG.HIVA(2auxo) vaccine in combination with modified vaccinia virus Ankara (MVA). HIVA was safe and induced HIV-1 and Mycobacterium tuberculosis-specific interferon-γ-producing T-cell responses in adult BALB/c mice. Polyfunctional HIV-1-specific CD8+ T cells, which produce interferon-γ and tumor necrosis factor-α and express the degranulation marker CD107a, were induced. Thus, we engineered a novel, safer, good laboratory practice-compatible BCG-vectored vaccine using prototype immunogen HIVA. This antibiotic-free plasmid selection system based on "double" auxotrophic complementation might be a new mycobacterial vaccine platform to develop not only recombinant BCG-based vaccines expressing second generation of HIV-1 immunogens but also other major pediatric pathogens to prime protective response soon after birth.

Published
2014
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