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1. Sustained aviremia despite anti-retroviral therapy non-adherence in male children after in utero HIV transmission

Author

Bengu, Nomonde, Cromhout, Gabriela, Adland, Emily, Govender, Katya, Herbert, Nicholas, Lim, Nicholas, Fillis, Rowena, Sprenger, Kenneth, Vieira, Vinicius, Kannie, Samantha, van Lobenstein, Jeroen, Chinniah, Kogielambal, Kapongo, Constant, Bhoola, Roopesh, Krishna, Malini, Mchunu, Noxolo, Pascucci, Giuseppe Rubens, Cotugno, Nicola, Palma, Paolo, Tagarro, Alfredo, Rojo, Pablo, Roider, Julia, Garcia-Guerrero, Maria C., Ochsenbauer, Christina, Groll, Andreas, Reddy, Kavidha, Giaquinto, Carlo, Rossi, Paolo, Hong, Seohyun, Dong, Krista, Ansari, M. Azim, Puertas, Maria C., Ndung’u, Thumbi, Capparelli, Edmund, Lichterfeld, Mathias, Martinez-Picado, Javier, Kappes, John C., Archary, Moherndran, and Goulder, Philip

Published
2024
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2. Sustained aviraemia despite anti-retroviral therapy non-adherence in male children following in utero hiv transmission

Author

Bengu, Nomonde, primary, Cromhout, Gabriela, additional, Adland, Emily, additional, Govender, Katya, additional, Herbert, Nicholas, additional, Lim, Nicholas, additional, Fillis, Rowena, additional, Sprenger, Kenneth, additional, Vieira, Vinicius, additional, Kannie, Samantha, additional, van Lobenstein, Jeroen, additional, Chinniah, Kogielambal, additional, Kapongo, Constant, additional, Bhoola, Roopesh, additional, Krishna, Malini, additional, Mchunu, Noxolo, additional, Pascucci, Giuseppe Rubens, additional, Cotugno, Nicola, additional, Palma, Paolo, additional, Tagarro, Alfredo, additional, Rojo, Pablo, additional, Roider, Julia, additional, Garcia-Guerrero, Maria C., additional, Ochsenbauer, Christina, additional, Groll, Andreas, additional, Reddy, Kavidha, additional, Giaquinto, Carlo, additional, Rossi, Paolo, additional, Hong, Seohyun, additional, Dong, Krista, additional, Ansari, M. Azim, additional, Puertas, Maria C., additional, Ndung’u, Thumbi, additional, Capparelli, Edmund, additional, Lichterfeld, Mathias, additional, Martinez-Picado, Javier, additional, Kappes, John C., additional, Archary, Moherndran, additional, and Goulder, Philip, additional

Published
2024
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3. Divergent trajectories of antiviral memory after SARS-CoV-2 infection

Author

Tomic, Adriana, Skelly, Donal T., Ogbe, Ane, O’Connor, Daniel, Pace, Matthew, Adland, Emily, Alexander, Frances, Ali, Mohammad, Allott, Kirk, Azim Ansari, M., Belij-Rammerstorfer, Sandra, Bibi, Sagida, Blackwell, Luke, Brown, Anthony, Brown, Helen, Cavell, Breeze, Clutterbuck, Elizabeth A., de Silva, Thushan, Eyre, David, Lumley, Sheila, Flaxman, Amy, Grist, James, Hackstein, Carl-Philipp, Halkerston, Rachel, Harding, Adam C., Hill, Jennifer, James, Tim, Jay, Cecilia, Johnson, Síle A., Kronsteiner, Barbara, Lie, Yolanda, Linder, Aline, Longet, Stephanie, Marinou, Spyridoula, Matthews, Philippa C., Mellors, Jack, Petropoulos, Christos, Rongkard, Patpong, Sedik, Cynthia, Silva-Reyes, Laura, Smith, Holly, Stockdale, Lisa, Taylor, Stephen, Thomas, Stephen, Tipoe, Timothy, Turtle, Lance, Vieira, Vinicius Adriano, Wrin, Terri, Pollard, Andrew J., Lambe, Teresa, Conlon, Chris P., Jeffery, Katie, Travis, Simon, Goulder, Philip, Frater, John, Mentzer, Alex J., Stafford, Lizzie, Carroll, Miles W., James, William S., Klenerman, Paul, Barnes, Eleanor, Dold, Christina, and Dunachie, Susanna J.

Published
2022
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4. Differential Immunodominance Hierarchy of CD8+ T-Cell Responses in HLA-B*27:05- and -B*27:02-Mediated Control of HIV-1 Infection

Author

Adland, Emily, Hill, Matilda, Lavandier, Nora, Csala, Anna, Edwards, Anne, Chen, Fabian, Radkowski, Marek, Kowalska, Justyna D, Paraskevis, Dimitrios, Hatzakis, Angelos, Valenzuela-Ponce, Humberto, Pfafferott, Katja, Williams, Ian, Pellegrino, Pierre, Borrow, Persephone, Mori, Masahiko, Rockstroh, Jürgen, Prado, Julia G, Mothe, Beatriz, Dalmau, Judith, Martinez-Picado, Javier, Tudor-Williams, Gareth, Frater, John, Stryhn, Anette, Buus, Soren, Teran, Gustavo Reyes, Mallal, Simon, John, Mina, Buchbinder, Susan, Kirk, Gregory, Martin, Jeffrey, Michael, Nelson, Fellay, Jacques, Deeks, Steve, Walker, Bruce, Avila-Rios, Santiago, Cole, David, Brander, Christian, Carrington, Mary, and Goulder, Philip

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Sexually Transmitted Infections, Infectious Diseases, HIV/AIDS, Clinical Research, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, CD8-Positive T-Lymphocytes, Genes, MHC Class I, HIV Infections, HIV-1, HLA-B27 Antigen, Humans, Immunodominant Epitopes, Viral Load, gag Gene Products, Human Immunodeficiency Virus, nef Gene Products, Human Immunodeficiency Virus, CD8(+) T cell, HIV Gag, HIV Nef, HLA, HLA-B*27, human immunodeficiency virus, CD8+ T cell, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract

The well-characterized association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05-restricted CD8+ T-cell responses toward the conserved Gag KK10 (residues 263 to 272) and polymerase (Pol) KY9 (residues 901 to 909) epitopes. We studied the impact of the 3 amino acid differences between HLA-B*27:05 and the closely related HLA-B*27:02 on the HIV-specific CD8+ T-cell response hierarchy and on immune control of HIV. Genetic epidemiological data indicate that both HLA-B*27:02 and HLA-B*27:05 are associated with slower disease progression and lower viral loads. The effect of HLA-B*27:02 appeared to be consistently stronger than that of HLA-B*27:05. In contrast to HLA-B*27:05, the immunodominant HIV-specific HLA-B*27:02-restricted CD8+ T-cell response is to a Nef epitope (residues 142 to 150 [VW9]), with Pol KY9 subdominant and Gag KK10 further subdominant. This selection was driven by structural differences in the F pocket, mediated by a polymorphism between these two HLA alleles at position 81. Analysis of autologous virus sequences showed that in HLA-B*27:02-positive subjects, all three of these CD8+ T-cell responses impose selection pressure on the virus, whereas in HLA-B*27:05-positive subjects, there is no Nef VW9-mediated selection pressure. These studies demonstrate that HLA-B*27:02 mediates protection against HIV disease progression that is at least as strong as or stronger than that mediated by HLA-B*27:05. In combination with the protective Gag KK10 and Pol KY9 CD8+ T-cell responses that dominate HIV-specific CD8+ T-cell activity in HLA-B*27:05-positive subjects, a Nef VW9-specific response is additionally present and immunodominant in HLA-B*27:02-positive subjects, mediated through a polymorphism at residue 81 in the F pocket, that contributes to selection pressure against HIV.IMPORTANCE CD8+ T cells play a central role in successful control of HIV infection and have the potential also to mediate the eradication of viral reservoirs of infection. The principal means by which protective HLA class I molecules, such as HLA-B*27:05 and HLA-B*57:01, slow HIV disease progression is believed to be via the particular HIV-specific CD8+ T cell responses restricted by those alleles. We focus here on HLA-B*27:05, one of the best-characterized protective HLA molecules, and the closely related HLA-B*27:02, which differs by only 3 amino acids and which has not been well studied in relation to control of HIV infection. We show that HLA-B*27:02 is also protective against HIV disease progression, but the CD8+ T-cell immunodominance hierarchy of HLA-B*27:02 differs strikingly from that of HLA-B*27:05. These findings indicate that the immunodominant HLA-B*27:02-restricted Nef response adds to protection mediated by the Gag and Pol specificities that dominate anti-HIV CD8+ T-cell activity in HLA-B*27:05-positive subjects.

Published
2018

5. Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in HIV infection: a single-arm substudy of a phase 2/3 clinical trial

Author

Watson, Marion E.E., Song, Rinn, Cicconi, Paola, Minassian, Angela M., Bibi, Sagida, Kerridge, Simon, Singh, Nisha, Green, Catherine M., Douglas, Alexander D., Lawrie, Alison M., Clutterbuck, Elizabeth A., Frater, John, Ewer, Katie J, Ogbe, Ane, Pace, Mathew, Adele, Sandra, Adland, Emily, Alagaratnam, Jasmini, Aley, Parvinder K, Ali, Mohammad, Ansari, M Azim, Bara, Anna, Bittaye, Mustapha, Broadhead, Samantha, Brown, Anthony, Brown, Helen, Cappuccini, Federica, Cooney, Enya, Dejnirattisai, Wanwisa, Dold, Christina, Fairhead, Cassandra, Fok, Henry, Folegatti, Pedro M, Fowler, Jamie, Gibbs, Charlotte, Goodman, Anna L, Jenkin, Daniel, Jones, Mathew, Makinson, Rebecca, Marchevsky, Natalie G, Mujadidi, Yama F, Nguyen, Hanna, Parolini, Lucia, Petersen, Claire, Plested, Emma, Pollock, Katrina M, Ramasamy, Maheshi N, Rhead, Sarah, Robinson, Hannah, Robinson, Nicola, Rongkard, Patpong, Ryan, Fiona, Serrano, Sonia, Tipoe, Timothy, Voysey, Merryn, Waters, Anele, Zacharopoulou, Panagiota, Barnes, Eleanor, Dunachie, Susanna, Goulder, Philip, Klenerman, Paul, Screaton, Gavin R, Winston, Alan, Hill, Adrian V S, Gilbert, Sarah C, Pollard, Andrew J, Fidler, Sarah, Fox, Julie, and Lambe, Teresa

Published
2021
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6. Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection

Author

Gatanaga, Hiroyuki, Brumme, Zabrina L, Adland, Emily, Reyes-Terán, Gustavo, Avila-Rios, Santiago, Mejía-Villatoro, Carlos R, Hayashida, Tsunefusa, Chikata, Takayuki, Van Tran, Giang, Van Nguyen, Kinh, Meza, Rita I, Palou, Elsa Y, Valenzuela-Ponce, Humberto, Pascale, Juan M, Porras-Cortés, Guillermo, Manzanero, Marvin, Lee, Guinevere Q, Martin, Jeffrey N, Carrington, Mary N, John, Mina, Mallal, Simon, Poon, Art FY, Goulder, Philip, Takiguchi, Masafumi, and Oka, Shinichi

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Prevention, HIV/AIDS, Sexually Transmitted Infections, Genetics, Infectious Diseases, 2.4 Surveillance and distribution, Aetiology, Infection, Anti-Retroviral Agents, Drug Resistance, Viral, Global Health, HIV Infections, HIV Reverse Transcriptase, HIV-1, HLA-B18 Antigen, Humans, Immune Evasion, Mutation, Missense, Polymorphism, Genetic, Pre-Exposure Prophylaxis, Rilpivirine, E138X, escape mutation, human leukocyte antigen-B*18, replication fitness, rilpivirine, International HIV Adaptation Collaborative, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Virology, Biomedical and clinical sciences, Health sciences
Abstract

ObjectiveLong-acting rilpivirine is a candidate for preexposure prophylaxis (PrEP) for prevention of HIV-1 infection. However, rilpivirine resistance mutations at reverse transcriptase codon 138 (E138X) occur naturally in a minority of HIV-1-infected persons; in particular those expressing human leukocyte antigen (HLA)-B18 where reverse transcriptase-E138X arises as an immune escape mutation. We investigate the global prevalence, B18-linkage and replicative cost of reverse transcriptase-E138X and its regional implications for rilpivirine PrEP.MethodsWe analyzed linked reverse transcriptase-E138X/HLA data from 7772 antiretroviral-naive patients from 16 cohorts spanning five continents and five HIV-1 subtypes, alongside unlinked global reverse transcriptase-E138X and HLA frequencies from public databases. E138X-containing HIV-1 variants were assessed for in-vitro replication as a surrogate of mutation stability following transmission.ResultsReverse transcriptase-E138X variants, where the most common were rilpivirine resistance-associated mutations E138A/G/K, were significantly enriched in HLA-B18-positive individuals globally (P = 3.5 × 10) and in all HIV-1 subtypes except A. Reverse transcriptase-E138X and B18 frequencies correlated positively in 16 cohorts with linked HIV/HLA genotypes (Spearman's R = 0.75; P = 7.6 × 10) and in unlinked HIV/HLA data from 43 countries (Spearman's R = 0.34, P = 0.02). Notably, reverse transcriptase-E138X frequencies approached (or exceeded) 10% in key epidemic regions (e.g. sub-Saharan Africa, Southeastern Europe) where B18 is more common. This, along with the observation that reverse transcriptase-E138X variants do not confer in-vitro replicative costs, supports their persistence, and ongoing accumulation in circulation over time.ConclusionsResults illustrate the potential for a natural immune-driven HIV-1 polymorphism to compromise antiretroviral-based prevention, particularly in key epidemic regions. Regional reverse transcriptase-E138X surveillance should be undertaken before use of rilpivirine PrEP.

Published
2017

7. Predictable patterns of CTL escape and reversion across host populations and viral subtypes in HIV-1 evolution

Author

Palmer, Duncan S., Adland, Emily, Frater, John A., Goulder, Philip J. R., Ndung'u, Thumbi, Matthews, Philippa C., Phillips, Rodney E., Shapiro, Roger, McVean, Gil, and McLean, Angela R.

Subjects
Quantitative Biology - Populations and Evolution
Abstract

The twin processes of viral evolutionary escape and reversion in response to host immune pressure, in particular the cytotoxic T-lymphocyte (CTL) response, shape Human Immunodeficiency Virus-1 sequence evolution in infected host populations. The tempo of CTL escape and reversion is known to differ between CTL escape variants in a given host population. Here, we ask: are rates of escape and reversion comparable across infected host populations? For three cohorts taken from three continents, we estimate escape and reversion rates at 23 escape sites in optimally defined Gag epitopes. We find consistent escape rate estimates across the examined cohorts. Reversion rates are also consistent between a Canadian and South African infected host population. Certain Gag escape variants that incur a large replicative fitness cost are known to revert rapidly upon transmission. However, the relationship between escape/reversion rates and viral replicative capacity across a large number of epitopes has not been interrogated. We investigate this relationship by examining $in$ $vitro$ replicative capacities of viral sequences with minimal variation: point escape mutants induced in a lab strain. Remarkably, despite the complexities of epistatic effects exemplified by pathways to escape in famous epitopes, and the diversity of both hosts and viruses, CTL escape mutants which escape rapidly tend to be those with the highest replicative capacity when applied as a single point mutation. Similarly, mutants inducing the greatest costs to viral replicative capacity tend to revert more quickly. These data suggest that escape rates in Gag are consistent across host populations, and that in general these rates are dominated by site specific effects upon viral replicative capacity.

Published
2015

8. HIGH-FREQUENCY failure of combination antiretroviral therapy in paediatric HIV infection is associated with unmet maternal needs causing maternal NON-ADHERENCE

Author

Millar, Jane R., Bengu, Nomonde, Fillis, Rowena, Sprenger, Ken, Ntlantsana, Vuyokazi, Vieira, Vinicius A., Khambati, Nisreen, Archary, Moherndran, Muenchhoff, Maximilian, Groll, Andreas, Grayson, Nicholas, Adamson, John, Govender, Katya, Dong, Krista, Kiepiela, Photini, Walker, Bruce D., Bonsall, David, Connor, Thomas, Bull, Matthew J., Nxele, Nelisiwe, Roider, Julia, Ismail, Nasreen, Adland, Emily, Puertas, Maria C., Martinez-Picado, Javier, Matthews, Philippa C., Ndung'u, Thumbi, and Goulder, Philip

Published
2020
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9. Gonadal androgens are associated with decreased type I interferon production by plasmacytoid dendritic cells and increased IgG titres to BNT162b2 following co-vaccination with live attenuated influenza vaccine in adolescents

Author

Sampson, Oliver L., primary, Jay, Cecilia, additional, Adland, Emily, additional, Csala, Anna, additional, Lim, Nicholas, additional, Ebbrecht, Stella M., additional, Gilligan, Lorna C., additional, Taylor, Angela E., additional, George, Sherley Sherafin, additional, Longet, Stephanie, additional, Jones, Lucy C., additional, Barnes, Ellie, additional, Frater, John, additional, Klenerman, Paul, additional, Dunachie, Susie, additional, Carrol, Miles, additional, Hawley, James, additional, Arlt, Wiebke, additional, Groll, Andreas, additional, and Goulder, Philip, additional

Published
2024
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10. Mechanisms of non-progressing paediatric HIV-1 infection

Author

Adland, Emily and Goulder, Philip

Subjects
618.92
Abstract

HIV-infected children progress more rapidly to AIDS than adults and, in sub-Saharan Africa, without antiretroviral therapy (ART), more than 50% will die before their second birthday. However, a minority of perinatally infected children will become paediatric non-progressors (PNP). The reasons for this rapid disease progression and the immunological correlates of protection against rapid progression are incompletely understood. This thesis focuses principally on paediatric HIV infection, and addresses the immunological and viral influences on disease progression. This work shows that Human Leukocyte Antigen (HLA) class I variation does not significantly influence progression rates in paediatric HIV infection, in stark contrast to adult HIV infection where HLA class I allele variation substantially impacts disease progression. This study describes potent broadly neutralizing antibody responses along with strong virus-specific T-cell activity in HIV-infected children. These virus-specific immune responses, however, do not protect against progression. The primary driver of non-progression in HIV infected children is low levels of T cell immune activation despite persistently high viraemia. This suggests close similarities with mechanisms evolved over thousands of years of non-pathogenic SIV infection in non-human primates. Further evaluation of the mechanisms underlying paediatric non-progression is relevant both to reaching a better understanding of HIV pathogenesis and to underpin future HIV cure strategies.

Published
2015

11. Robust HIV-specific CD4+ and CD8+ T-cell responses distinguish the rare phenotype of elite control in adolescents living with HIV from viraemic non-progressors

Author

Vieira, Vinicius A., Millar, Jane, Adland, Emily, Muenchhoff, Maximilian, Roider, Julia, Guash, Claudia Fortuny, Peluso, Denise, Thomé, Beatriz, Garcia-Guerrero, Maria C., Puertas, Mari C., Bamford, Alasdair, Brander, Christian, Carrington, Mary, Martinez-Picado, Javier, Frater, John, Tudor-Williams, Gareth, and Goulder, Philip

Published
2021
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12. Robust HIV-specific CD4+ and CD8+ T-cell responses distinguish elite control in adolescents living with HIV from viremic nonprogressors

Author

Vieira, Vinicius A., Millar, Jane, Adland, Emily, Muenchhoff, Maximilian, Roider, Julia, Guash, Claudia Fortuny, Peluso, Denise, Thomé, Beatriz, Garcia-Guerrero, Maria C., Puertas, Mari C., Bamford, Alasdair, Brander, Christian, Carrington, Mary, Martinez-Picado, Javier, Frater, John, Tudor-Williams, Gareth, and Goulder, Philip

Published
2022
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13. Age- and sex-specific differences in immune responses to BNT162b2 COVID-19 and live-attenuated influenza vaccines in UK adolescents

Author

Jay, Cecilia, primary, Adland, Emily, additional, Csala, Anna, additional, Lim, Nicholas, additional, Longet, Stephanie, additional, Ogbe, Ane, additional, Ratcliff, Jeremy, additional, Sampson, Oliver, additional, Thompson, Craig P., additional, Turtle, Lance, additional, Barnes, Eleanor, additional, Dunachie, Susanna, additional, Klenerman, Paul, additional, Carroll, Miles, additional, and Goulder, Philip, additional

Published
2023
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14. Cellular immunity to SARS-CoV-2 following intrafamilial exposure in seronegative family members

Author

Jay, Cecilia, primary, Adland, Emily, additional, Csala, Anna, additional, Dold, Christina, additional, Edmans, Matthew, additional, Hackstein, Carl-Philipp, additional, Jamsen, Anni, additional, Lim, Nicholas, additional, Longet, Stephanie, additional, Ogbe, Ane, additional, Sampson, Oliver, additional, Skelly, Donal, additional, Spiller, Owen B., additional, Stafford, Lizzie, additional, Thompson, Craig P., additional, Turtle, Lance, additional, Barnes, Ellie, additional, Dunachie, Susanna, additional, Carroll, Miles, additional, Klenerman, Paul, additional, Conlon, Chris, additional, Goulder, Philip, additional, and Jones, Lucy C., additional

Published
2023
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15. Gonadal androgens are associated with decreased type I interferon production by pDCs and increased IgG titres to BNT162b2 following co-vaccination with live attenuated influenza vaccine in adolescents

Author

Sampson, Oliver L, primary, Jay, Cecilia, additional, Adland, Emily, additional, Csala, Anna, additional, Lim, Nicholas, additional, Ebbrecht, Stella M, additional, Gilligan, Lorna C, additional, Taylor, Angela E, additional, George, Sherley Sherafin, additional, Longet, Stephanie, additional, Jones, Lucy C, additional, Barnes, Ellie, additional, Frater, John, additional, Klenerman, Paul, additional, Dunachie, Susanna, additional, Carroll, Miles W, additional, Hawley, James, additional, Arlt, Wiebke, additional, Groll, Andreas, additional, and Goulder, Philip, additional

Published
2023
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16. Author Correction: Sex-specific innate immune selection of HIV-1 in utero is associated with increased female susceptibility to infection

Author

Adland, Emily, Millar, Jane, Bengu, Nomonde, Muenchhoff, Maximilian, Fillis, Rowena, Sprenger, Kenneth, Ntlantsana, Vuyokasi, Roider, Julia, Vieira, Vinicius, Govender, Katya, Adamson, John, Nxele, Nelisiwe, Ochsenbauer, Christina, Kappes, John, Mori, Luisa, van Lobenstein, Jeroen, Graza, Yeney, Chinniah, Kogielambal, Kapongo, Constant, Bhoola, Roopesh, Krishna, Malini, Matthews, Philippa C., Poderos, Ruth Penya, Lluch, Marta Colomer, Puertas, Maria C., Prado, Julia G., McKerrow, Neil, Archary, Moherndran, Ndung’u, Thumbi, Groll, Andreas, Jooste, Pieter, Martinez-Picado, Javier, Altfeld, Marcus, and Goulder, Philip

Published
2020
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17. Sex-specific innate immune selection of HIV-1 in utero is associated with increased female susceptibility to infection

Author

Adland, Emily, Millar, Jane, Bengu, Nomonde, Muenchhoff, Maximilian, Fillis, Rowena, Sprenger, Kenneth, Ntlantsana, Vuyokasi, Roider, Julia, Vieira, Vinicius, Govender, Katya, Adamson, John, Nxele, Nelisiwe, Ochsenbauer, Christina, Kappes, John, Mori, Luisa, van Lobenstein, Jeroen, Graza, Yeney, Chinniah, Kogielambal, Kapongo, Constant, Bhoola, Roopesh, Krishna, Malini, Matthews, Philippa C., Poderos, Ruth Penya, Lluch, Marta Colomer, Puertas, Maria C., Prado, Julia G., McKerrow, Neil, Archary, Moherndran, Ndung’u, Thumbi, Groll, Andreas, Jooste, Pieter, Martinez-Picado, Javier, Altfeld, Marcus, and Goulder, Philip

Published
2020
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18. Slow progression of pediatric HIV associates with early CD8+ T cell PD-1 expression and a stem-like phenotype

Author

Vieira, Vinicius, Lim, Nicholas, Singh, Alveera, Leitman, Ellen, Dsouza, Reena, Adland, Emily, Muenchhoff, Maximilian, Roider, Julia, Lopez, Miguel Marin, Carabelli, Julieta, Giandhari, Jennifer, Groll, Andreas, Jooste, Pieter, Prado, Julia G., Thobakgale, Christina, Dong, Krista, Kiepiela, Photini, Prendergast, Andrew J., Tudor-Williams, Gareth, Frater, John, Walker, Bruce D., Ndung'U, Thumbi, Ramsuran, Veron, Leslie, Alasdair, Kløverpris, Henrik N., Goulder, Philip, Vieira, Vinicius, Lim, Nicholas, Singh, Alveera, Leitman, Ellen, Dsouza, Reena, Adland, Emily, Muenchhoff, Maximilian, Roider, Julia, Lopez, Miguel Marin, Carabelli, Julieta, Giandhari, Jennifer, Groll, Andreas, Jooste, Pieter, Prado, Julia G., Thobakgale, Christina, Dong, Krista, Kiepiela, Photini, Prendergast, Andrew J., Tudor-Williams, Gareth, Frater, John, Walker, Bruce D., Ndung'U, Thumbi, Ramsuran, Veron, Leslie, Alasdair, Kløverpris, Henrik N., and Goulder, Philip

Abstract

HIV nonprogression despite persistent viremia is rare among adults who are naive to antiretroviral therapy (ART) but relatively common among ART-naive children. Previous studies indicate that ARTnaive pediatric slow progressors (PSPs) adopt immune evasion strategies similar to those described in natural hosts of SIV. However, the mechanisms underlying this immunophenotype are not well understood. In a cohort of early-treated infants who underwent analytical treatment interruption (ATI) after 12 months of ART, expression of PD-1 on CD8+ T cells immediately before ATI was the main predictor of slow progression during ATI. PD-1+CD8+ T cell frequency was also negatively correlated with CCR5 and HLA-DR expression on CD4+ T cells and predicted stronger HIV-specific T lymphocyte responses. In the CD8+ T cell compartment of PSPs, we identified an enrichment of stem-like TCF-1+PD-1+ memory cells, whereas pediatric progressors and viremic adults had a terminally exhausted PD-1+CD39+ population. TCF-1+PD-1+ expression on CD8+ T cells was associated with higher proliferative activity and stronger Gag-specific effector functionality. These data prompted the hypothesis that the proliferative burst potential of stem-like HIV-specific cytotoxic cells could be exploited in therapeutic strategies to boost the antiviral response and facilitate remission in infants who received early ART with a preserved and nonexhausted T cell compartment.

Published
2023

20. Strong sex bias in elite control of paediatric HIV infection

Author

Vieira, Vinicius A., Zuidewind, Peter, Muenchhoff, Maximilian, Roider, Julia, Millar, Jane, Clapson, Margaret, Van Zyl, Anriette, Shingadia, Delane, Adland, Emily, Athavale, Rohin, Grayson, Nicholas, Ansari, M. Azim, Brander, Christian, Guash, Claudia Fortuny, Naver, Lars, Puthanakit, Thanyawee, Songtaweesin, Wipaporn Natalie, Ananworanich, Jintanat, Peluso, Denise, Thomé, Beatriz, Pinto, Jorge, Jooste, Pieter, Tudor-Williams, Gareth, Cotton, Mark F., and Goulder, Philip

Published
2019
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22. Slow progression of pediatric HIV associates with early CD8+ T cell PD-1 expression and a stem-like phenotype

Author

Vieira, Vinicius, primary, Lim, Nicholas, additional, Singh, Alveera, additional, Leitman, Ellen, additional, Dsouza, Reena, additional, Adland, Emily, additional, Muenchhoff, Maximilian, additional, Roider, Julia, additional, Marin Lopez, Miguel, additional, Carabelli, Julieta, additional, Giandhari, Jennifer, additional, Groll, Andreas, additional, Jooste, Pieter, additional, Prado, Julia G., additional, Thobakgale, Christina, additional, Dong, Krista, additional, Kiepiela, Photini, additional, Prendergast, Andrew J., additional, Tudor-Williams, Gareth, additional, Frater, John, additional, Walker, Bruce D., additional, Ndung’u, Thumbi, additional, Ramsuran, Veron, additional, Leslie, Alasdair, additional, Kløverpris, Henrik N., additional, and Goulder, Philip, additional

Published
2023
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23. Impact of HLA-driven HIV adaptation on virulence in populations of high HIV seroprevalence

Author

Payne, Rebecca, Muenchhoff, Maximilian, Mann, Jaclyn, Roberts, Hannah E., Matthews, Philippa, Adland, Emily, Hempenstall, Allison, Huang, Kuan-Hsiang, Brockman, Mark, Brumme, Zabrina, Sinclair, Marc, Miura, Toshiyuki, Frater, John, Essex, Myron, Shapiro, Roger, Walker, Bruce D., Ndung'u, Thumbi, McLean, Angela R., Carlson, Jonathan M., and Goulder, Philip J. R.

Published
2014

26. Next-generation point-of-care testing in pediatric human immunodeficiency virus infection facilitates diagnosis and monitoring of treatment

Author

Bengu, Nomonde, primary, Mchunu, Noxolo, additional, Mokhethi, Sijabulile, additional, Fillis, Rowena, additional, Cromhout, Gabriela, additional, Lobenstein, Jeroen van, additional, Graza, Yeney, additional, Kapongo, Constant, additional, Chinniah, Kogielambal, additional, Bhoola, Roopesh, additional, Adland, Emily, additional, Puertas, Mari C., additional, Ndung’u, Thumbi, additional, Martinez-Picado, Javier, additional, Archary, Moherndran, additional, and Goulder, Philip J. R, additional

Published
2022
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28. A simple, robust flow cytometry-based whole blood assay for investigating sex differential interferon alpha production by plasmacytoid dendritic cells

Author

Sampson, Oliver, primary, Lim, Nicholas, additional, White, Jemima, additional, Vieira, Vinicius, additional, Kløverpris, Henrik, additional, Adland, Emily, additional, Conlon, Chris, additional, Skelly, Donal, additional, Jones, Lucy, additional, Stafford, Lizzie, additional, Jamsen, Anni, additional, Barnes, Ellie, additional, Dunachie, Susie, additional, Frater, John, additional, Klenerman, Paul, additional, Altfeld, Marcus, additional, and Goulder, Philip, additional

Published
2022
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29. Two Distinct Mechanisms Leading to Loss of Virological Control in the Rare Group of Antiretroviral Therapy-Naive, Transiently Aviremic Children Living with HIV

Author

Vieira, Vinicius A., primary, Adland, Emily, additional, Grayson, Nicholas E., additional, Csala, Anna, additional, Richards, Fa’eeda, additional, Dacon, Cherrelle, additional, Athavale, Rohin, additional, Tsai, Ming-Han, additional, D’Souza, Reena, additional, Muenchhoff, Maximilian, additional, Bonsall, David, additional, Jooste, Pieter, additional, and Goulder, Philip J. R., additional

Published
2022
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30. T-cell and antibody responses to first BNT162b2 vaccine dose in previously infected and SARS-CoV-2-naive UK health-care workers: a multicentre prospective cohort study

Author

Angyal, Adrienn, primary, Longet, Stephanie, additional, Moore, Shona C, additional, Payne, Rebecca P, additional, Harding, Adam, additional, Tipton, Tom, additional, Rongkard, Patpong, additional, Ali, Mohammad, additional, Hering, Luisa M, additional, Meardon, Naomi, additional, Austin, James, additional, Brown, Rebecca, additional, Skelly, Donal, additional, Gillson, Natalie, additional, Dobson, Sue L, additional, Cross, Andrew, additional, Sandhar, Gurjinder, additional, Kilby, Jonathan A, additional, Tyerman, Jessica K, additional, Nicols, Alexander R, additional, Spegarova, Jarmila S, additional, Mehta, Hema, additional, Hornsby, Hailey, additional, Whitham, Rachel, additional, Conlon, Christopher P, additional, Jeffery, Katie, additional, Goulder, Philip, additional, Frater, John, additional, Dold, Christina, additional, Pace, Matthew, additional, Ogbe, Ane, additional, Brown, Helen, additional, Ansari, M Azim, additional, Adland, Emily, additional, Brown, Anthony, additional, Chand, Meera, additional, Shields, Adrian, additional, Matthews, Philippa C, additional, Hopkins, Susan, additional, Hall, Victoria, additional, James, William, additional, Rowland-Jones, Sarah L, additional, Klenerman, Paul, additional, Dunachie, Susanna, additional, Richter, Alex, additional, Duncan, Christopher J A, additional, Barnes, Eleanor, additional, Carroll, Miles, additional, Turtle, Lance, additional, de Silva, Thushan I, additional, Watson, Adam, additional, Angyal, Adrienn, additional, Alhussni, Ahmed, additional, Nicols, Alexander, additional, Deeks, Alexandra, additional, Webb-Bridges, Alice, additional, Jämsén, Anni, additional, Chawla, Anu, additional, Duncan, Christopher, additional, Conlon, Christopher, additional, O'Donnell, Denise, additional, Weeks, Esme, additional, Abuelgasim, Hibatullah, additional, Xiao, Huiyuan, additional, Spegarova, Jarmila, additional, Holmes, Jennifer, additional, Haworth, Jenny, additional, Tyerman, Jessica, additional, Kilby, Jonathan, additional, Cutteridge, Joseph, additional, Lillie, Katy, additional, Romaniuk, Leigh, additional, Denly, Lucy, additional, Hering, Luisa, additional, Ansari, M. Azim, additional, Kasanyinga, Mwila, additional, Matthews, Philippa, additional, Payne, Rebecca, additional, Wilson, Robert, additional, Rowland-Jones, Sarah, additional, Thomas, Sarah, additional, Moore, Shona, additional, Gardiner, Siobhan, additional, Tucker, Stephanie, additional, Dobson, Sue, additional, Adlou, Syed, additional, de Silva, Thushan, additional, Lawrie, Allan, additional, Smith, Nikki, additional, Turton, Helena, additional, Zawia, Amira, additional, Bayley, Martin, additional, Fairman, Alex, additional, Harrington, Kate, additional, Kirk, Rosemary, additional, Marsh, Louise, additional, Watson, Lisa, additional, Wood, Steven, additional, Diffey, Benjamin, additional, Jones, Chris, additional, Lett, Lauren, additional, Platt, Gareth, additional, Subramaniam, Krishanthi, additional, Wootton, Daniel, additional, Payne, Brendan, additional, Hambleton, Sophie, additional, Kelly, Sinead, additional, Marston, Judith, additional, Poolan, Sonia, additional, Turner, Dianne, additional, Haniffa, Muzlifah, additional, Stephenson, Emily, additional, Adele, Sandra, additional, Akhter, Hossain Delowar, additional, Chinnakannan, Senthil, additional, de Lara, Catherine, additional, Donnison, Timothy, additional, Hackstein, Carl-Philipp, additional, Lee, Lian, additional, Lim, Nicholas, additional, Malone, Tom, additional, Phillips, Eloise, additional, Ramamurthy, Narayan, additional, Robinson, Nichola, additional, Sampson, Oliver, additional, Eyre, David, additional, Simmons, Beatrice, additional, Stafford, Lizzie, additional, Mentzer, Alexander, additional, Amini, Ali, additional, Arancibia-Cárcamo, Carolina, additional, Provine, Nicholas, additional, Travis, Simon, additional, Dimitriadis, Stavros, additional, Johnson, Sile, additional, Foulkes, Sarah, additional, Khawam, Jameel, additional, Wellington, Edgar, additional, Gilbert-Jaramillo, Javier, additional, Knight, Michael, additional, Dupont, Maeva, additional, Horner, Emily, additional, Thaventhiran, James, additional, and Chalk, Jeremy, additional

Published
2022
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31. Two doses of SARS-CoV-2 vaccination induce robust immune responses to emerging SARS-CoV-2 variants of concern

Author

Skelly, Donal T, Harding, Adam C, Gilbert-Jaramillo, Javier, Knight, Michael L, Longet, Stephanie, Brown, Anthony, Adele, Sandra, Adland, Emily, Brown, Helen, Chinnakannan, Senthil, Donnison, Timothy, Ali, Mohammad, Rongkard, Patpong, Pace, Matthew, Zacharopoulou, Peny, Robinson, Nicola, Csala, Anna, De Lara, Cathy, Hutchings, Claire L, Mehta, Hema, Lee, Lian Ni, Edmans, Matthew, Hackstein, Carl-Philipp, Phalora, Prabhjeet, Li, Wenqin, Phillips, Eloise, Malone, Tom, Ogbe, Ane, Jay, Cecilia, Tipoe, Timothy, Tipton, Tom, Stafford, Lizzie, Mentzer, Alexander J, Johnson, Sile A, Amini, Ali, Marjot, Thomas, Dimitriadis, Stavros, Simmons, Beatrice, Deeks, Alexandra, Kerneis, Sven, Abuelgasim, Hibatullah, Wilson, Robert, Thomas, Sarah R, Watson, Adam, Alhussni, Ahmed, Cutteridge, Joseph, Weeks, Esme, Denly, Lucy, Lillie, Katy, Holmes, Jennifer, Matthews, Philppa C, O'Donnell, Denise, Tan, Tiong Kit, Schimanski, Lisa, Huang, Kuan-Ying A, Rijal, Pramila, Turtle, Lance, de Silva, Thushan, Richter, Alex, Duncan, Christopher JA, Payne, Rebecca P, Moore, Shona C, Knight, Julian C, Cassar, Mark Philip, Raman, Betty, Neubauer, Stefan, Fries, Anastasia, Talbot, Nick P, Petousi, Nayia, Ho, Ling-Pei, Peng, Yanchun, Dong, Tao, Camara, Susana, Marinou, Spyridoula, Linder, Aline, Adlou, Syed, Kasanyinga, Mwila, Bridges-Webb, Alice, Hill, Jennifer, Silva-Reyes, Laura, Blackwell, Luke, Frater, John, Goulder, Philip, Conlon, Christopher P, Jeffery, Katie, Dold, Christina, Pollard, Andrew J, Sigal, Alex, de Oliveira, Tulio, Townsend, Alain R, Klenerman, Paul, Dunachie, Susanna J, Barnes, Eleanor, Carroll, Miles W, James, William S, Team, Medawar Lab, OPTIC, PITCH, and PHOSP

Subjects
COVID-19 Vaccines, T cell, viruses, Science, T-Lymphocytes, General Physics and Astronomy, Biology, Antibodies, Viral, General Biochemistry, Genetics and Molecular Biology, Neutralization, Epitope, Article, Epitopes, Immune system, Immunity, medicine, Animals, Humans, skin and connective tissue diseases, Vaccines, Multidisciplinary, SARS-CoV-2, fungi, Antibodies, Monoclonal, COVID-19, General Chemistry, Antimicrobial responses, biochemical phenomena, metabolism, and nutrition, Virology, Antibodies, Neutralizing, Vaccination, body regions, medicine.anatomical_structure, Immunization, biology.protein, Angiotensin-Converting Enzyme 2, Antibody, Pathogens, Carrier Proteins
Abstract

The extent to which immune responses to natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and immunization with vaccines protect against variants of concern (VOC) is of increasing importance. Accordingly, here we analyse antibodies and T cells of a recently vaccinated, UK cohort, alongside those recovering from natural infection in early 2020. We show that neutralization of the VOC compared to a reference isolate of the original circulating lineage, B, is reduced: more profoundly against B.1.351 than for B.1.1.7, and in responses to infection or a single dose of vaccine than to a second dose of vaccine. Importantly, high magnitude T cell responses are generated after two vaccine doses, with the majority of the T cell response directed against epitopes that are conserved between the prototype isolate B and the VOC. Vaccination is required to generate high potency immune responses to protect against these and other emergent variants., Understanding the effect of vaccination on emerging SARS-CoV-2 variants of concern is of increasing importance. Here, James et al. report that two doses of vaccination with the Pfizer-BioNTech vaccine induce more robust immune responses to the B.1.1.7 and B.1.351 SARS-CoV-2 lineages than does natural infection.

Published
2021

32. An HLA-I signature favouring KIR-educated Natural Killer cells mediates immune control of HIV in children and contrasts with the HLA-B-restricted CD8+ T-cell-mediated immune control in adults

Author

Vieira, Vinicius A., primary, Adland, Emily, additional, Malone, David F. G., additional, Martin, Maureen P., additional, Groll, Andreas, additional, Ansari, M. Azim, additional, Garcia-Guerrero, Maria C., additional, Puertas, Mari C., additional, Muenchhoff, Maximilian, additional, Guash, Claudia Fortuny, additional, Brander, Christian, additional, Martinez-Picado, Javier, additional, Bamford, Alasdair, additional, Tudor-Williams, Gareth, additional, Ndung’u, Thumbi, additional, Walker, Bruce D., additional, Ramsuran, Veron, additional, Frater, John, additional, Jooste, Pieter, additional, Peppa, Dimitra, additional, Carrington, Mary, additional, and Goulder, Philip J. R., additional

Published
2021
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33. Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

Author

Payne, Rebecca P., primary, Longet, Stephanie, additional, Austin, James A., additional, Skelly, Donal T., additional, Dejnirattisai, Wanwisa, additional, Adele, Sandra, additional, Meardon, Naomi, additional, Faustini, Sian, additional, Al-Taei, Saly, additional, Moore, Shona C., additional, Tipton, Tom, additional, Hering, Luisa M., additional, Angyal, Adrienn, additional, Brown, Rebecca, additional, Nicols, Alexander R., additional, Gillson, Natalie, additional, Dobson, Susan L., additional, Amini, Ali, additional, Supasa, Piyada, additional, Cross, Andrew, additional, Bridges-Webb, Alice, additional, Reyes, Laura Silva, additional, Linder, Aline, additional, Sandhar, Gurjinder, additional, Kilby, Jonathan A., additional, Tyerman, Jessica K., additional, Altmann, Thomas, additional, Hornsby, Hailey, additional, Whitham, Rachel, additional, Phillips, Eloise, additional, Malone, Tom, additional, Hargreaves, Alexander, additional, Shields, Adrian, additional, Saei, Ayoub, additional, Foulkes, Sarah, additional, Stafford, Lizzie, additional, Johnson, Sile, additional, Wootton, Daniel G., additional, Conlon, Christopher P., additional, Jeffery, Katie, additional, Matthews, Philippa C., additional, Frater, John, additional, Deeks, Alexandra S., additional, Pollard, Andrew J., additional, Brown, Anthony, additional, Rowland-Jones, Sarah L., additional, Mongkolsapaya, Juthathip, additional, Barnes, Eleanor, additional, Hopkins, Susan, additional, Hall, Victoria, additional, Dold, Christina, additional, Duncan, Christopher J.A., additional, Richter, Alex, additional, Carroll, Miles, additional, Screaton, Gavin, additional, de Silva, Thushan I., additional, Turtle, Lance, additional, Klenerman, Paul, additional, Dunachie, Susanna, additional, Abuelgasim, Hibatullah, additional, Adland, Emily, additional, Adlou, Syed, additional, Akther, Hossain Delowar, additional, Alhussni, Ahmed, additional, Ali, Mohammad, additional, Ansari, M. Azim, additional, Arancibia-Cárcamo, Carolina V., additional, Bayley, Martin, additional, Brown, Helen, additional, Chalk, Jeremy, additional, Chand, Meera, additional, Chawla, Anu, additional, Chinnakannan, Senthil, additional, Cutteridge, Joseph, additional, de Lara, Catherine, additional, Denly, Lucy, additional, Diffey, Ben, additional, Dimitriadis, Stavros, additional, Drake, Thomas M., additional, Donnison, Timothy, additional, Dupont, Maeva, additional, Eyre, David, additional, Fairman, Alex, additional, Gardiner, Siobhan, additional, Gilbert-Jarmillo, Javier, additional, Goulder, Philip, additional, Hackstein, Carl-Philipp, additional, Hambleton, Sophie, additional, Haniffa, Muzlifah, additional, Haworth, Jenny, additional, Holmes, Jennifer, additional, Horner, Emily, additional, Jämsén, Anni, additional, Jones, Chris, additional, Kasanyinga, Mwila, additional, Kelly, Sinead, additional, Kirk, Rosemary, additional, Knight, Michael L., additional, Lawrie, Allan, additional, Lee, Lian, additional, Lett, Lauren, additional, Lillie, Katy, additional, Lim, Nicholas, additional, Mehta, Hema, additional, Mentzer, Alexander J., additional, O’Donnell, Denise, additional, Ogbe, Ane, additional, Pace, Matthew, additional, Payne, Brendan A.I., additional, Platt, Gareth, additional, Poolan, Sonia, additional, Provine, Nicholas, additional, Ramamurthy, Narayan, additional, Robinson, Nichola, additional, Romaniuk, Leigh, additional, Rongkard, Patpong, additional, Sampson, Oliver L., additional, Simmons, Beatrice, additional, Spegarova, Jarmila S., additional, Stephenson, Emily, additional, Subramaniam, Kris, additional, Thaventhiran, James, additional, Thomas, Sarah, additional, Travis, Simon, additional, Tucker, Stephanie, additional, Turton, Helena, additional, Watson, Adam, additional, Watson, Lisa, additional, Weeks, Esme, additional, Wilson, Robert, additional, Wood, Steven, additional, Wright, Rachel, additional, Xiao, Huiyuan, additional, and Zawia, Amira A.T., additional

Published
2021
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34. Robust HIV-specific CD4+ and CD8+ T-cell responses distinguish elite control in adolescents living with HIV from viremic nonprogressors

Author

Vieira, Vinicius A., primary, Millar, Jane, additional, Adland, Emily, additional, Muenchhoff, Maximilian, additional, Roider, Julia, additional, Guash, Claudia Fortuny, additional, Peluso, Denise, additional, Thomé, Beatriz, additional, Garcia-Guerrero, Maria C., additional, Puertas, Mari C., additional, Bamford, Alasdair, additional, Brander, Christian, additional, Carrington, Mary, additional, Martinez-Picado, Javier, additional, Frater, John, additional, Tudor-Williams, Gareth, additional, and Goulder, Philip, additional

Published
2021
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35. Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in HIV infection: a single-arm substudy of a phase 2/3 clinical trial

Author

Frater, John, primary, Ewer, Katie J, additional, Ogbe, Ane, additional, Pace, Mathew, additional, Adele, Sandra, additional, Adland, Emily, additional, Alagaratnam, Jasmini, additional, Aley, Parvinder K, additional, Ali, Mohammad, additional, Ansari, M Azim, additional, Bara, Anna, additional, Bittaye, Mustapha, additional, Broadhead, Samantha, additional, Brown, Anthony, additional, Brown, Helen, additional, Cappuccini, Federica, additional, Cooney, Enya, additional, Dejnirattisai, Wanwisa, additional, Dold, Christina, additional, Fairhead, Cassandra, additional, Fok, Henry, additional, Folegatti, Pedro M, additional, Fowler, Jamie, additional, Gibbs, Charlotte, additional, Goodman, Anna L, additional, Jenkin, Daniel, additional, Jones, Mathew, additional, Makinson, Rebecca, additional, Marchevsky, Natalie G, additional, Mujadidi, Yama F, additional, Nguyen, Hanna, additional, Parolini, Lucia, additional, Petersen, Claire, additional, Plested, Emma, additional, Pollock, Katrina M, additional, Ramasamy, Maheshi N, additional, Rhead, Sarah, additional, Robinson, Hannah, additional, Robinson, Nicola, additional, Rongkard, Patpong, additional, Ryan, Fiona, additional, Serrano, Sonia, additional, Tipoe, Timothy, additional, Voysey, Merryn, additional, Waters, Anele, additional, Zacharopoulou, Panagiota, additional, Barnes, Eleanor, additional, Dunachie, Susanna, additional, Goulder, Philip, additional, Klenerman, Paul, additional, Screaton, Gavin R, additional, Winston, Alan, additional, Hill, Adrian V S, additional, Gilbert, Sarah C, additional, Pollard, Andrew J, additional, Fidler, Sarah, additional, Fox, Julie, additional, Lambe, Teresa, additional, Watson, Marion E.E., additional, Song, Rinn, additional, Cicconi, Paola, additional, Minassian, Angela M., additional, Bibi, Sagida, additional, Kerridge, Simon, additional, Singh, Nisha, additional, Green, Catherine M., additional, Douglas, Alexander D., additional, Lawrie, Alison M., additional, and Clutterbuck, Elizabeth A., additional

Published
2021
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36. Epigenetic Features of HIV-Induced T-Cell Exhaustion Persist Despite Early Antiretroviral Therapy

Author

Martin, Genevieve E., primary, Sen, Debattama R., additional, Pace, Matthew, additional, Robinson, Nicola, additional, Meyerowitz, Jodi, additional, Adland, Emily, additional, Thornhill, John P., additional, Jones, Mathew, additional, Ogbe, Ane, additional, Parolini, Lucia, additional, Olejniczak, Natalia, additional, Zacharopoulou, Panagiota, additional, Brown, Helen, additional, Willberg, Christian B., additional, Nwokolo, Nneka, additional, Fox, Julie, additional, Fidler, Sarah, additional, Haining, W. Nicholas, additional, and Frater, John, additional

Published
2021
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37. Early Initiation of Antiretroviral Therapy Following In Utero HIV Infection Is Associated With Low Viral Reservoirs but Other Factors Determine Viral Rebound

Author

Millar, Jane R, primary, Bengu, Nomonde, additional, Vieira, Vinicius A, additional, Adland, Emily, additional, Roider, Julia, additional, Muenchhoff, Maximilian, additional, Fillis, Rowena, additional, Sprenger, Kenneth, additional, Ntlantsana, Vuyokazi, additional, Fatti, Isabella, additional, Archary, Moherndran, additional, Groll, Andreas, additional, Ismail, Nasreen, additional, García-Guerrero, Maria C, additional, Matthews, Philippa C, additional, Ndung’u, Thumbi, additional, Puertas, Maria C, additional, Martinez-Picado, Javier, additional, and Goulder, Philip, additional

Published
2021
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39. T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses

Author

Ogbe, Ane, Kronsteiner, Barbara, Skelly, Donal T, Pace, Matthew, Brown, Anthony, Adland, Emily, Adair, Kareena, Akhter, Hossain Delowar, Ali, Mohammad, Ali, Serat-E, Angyal, Adrienn, Ansari, M Azim, Arancibia-Carcamo, Carolina V, Brown, Helen, Chinnakannan, Senthil, Conlon, Christopher, de Lara, Catherine, de Silva, Thushan, Dold, Christina, Dong, Tao, Donnison, Timothy, Eyre, David, Flaxman, Amy, Fletcher, Helen, Gardner, Joshua, Grist, James T, Hackstein, Carl-Philipp, Jaruthamsophon, Kanoot, Jeffery, Katie, Lambe, Teresa, Lee, Lian, Li, Wenqin, Lim, Nicholas, Matthews, Philippa C, Mentzer, Alexander J, Moore, Shona C, Naisbitt, Dean J, Ogese, Monday, Ogg, Graham, Openshaw, Peter, Pirmohamed, Munir, Pollard, Andrew J, Ramamurthy, Narayan, Rongkard, Patpong, Rowland-Jones, Sarah, Sampson, Oliver, Screaton, Gavin, Sette, Alessandro, Stafford, Lizzie, Thompson, Craig, Thomson, Paul J, Thwaites, Ryan, Vieira, Vinicius, Weiskopf, Daniela, Zacharopoulou, Panagiota, Chalk, Jeremy, Kerr, Georgina, Phalora, Prabhjeet, Csala, Anna, Jones, Mathew, Robinson, Nicola, Brown, Rachael, Hutchings, Claire, Provine, Nicholas, Ratcliff, Jeremy, Amini, Ali, Borak, Martyna, Dimitriadis, Stavros, Fordwoh, Thomas, Horsington, Bryn, Johnson, Sile, Morrow, Jordan, Warren, Yolanda, Wells, Charlie, Turtle, Lance, Klenerman, Paul, Goulder, Philip, Frater, John, Barnes, Eleanor, Dunachie, Susanna, Immunology, Oxford, and Oxford, Protective TC

Subjects
0301 basic medicine, CD4-Positive T-Lymphocytes, animal diseases, T-Lymphocytes, General Physics and Astronomy, CD8-Positive T-Lymphocytes, Immunological memory, 0302 clinical medicine, 030212 general & internal medicine, Subclinical infection, Immunoassay, Multidisciplinary, ELISPOT, 3. Good health, Multidisciplinary Sciences, medicine.anatomical_structure, Science & Technology - Other Topics, VIRUS, Cytokines, Science, T cell, Health Personnel, Oxford Protective T Cell Immunology for COVID-19 (OPTIC) Clinical Team, chemical and pharmacologic phenomena, Biology, Cross Reactions, Antiviral Agents, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Interferon-gamma, Immune system, Antigen, Immunity, medicine, Humans, Pandemics, Cell Proliferation, Science & Technology, Cell growth, SARS-CoV-2, Oxford Immunology Network Covid-19 Response T Cell Consortium, COVID-19, General Chemistry, biochemical phenomena, metabolism, and nutrition, 030104 developmental biology, HEK293 Cells, Viral infection, Immunoglobulin G, Immunology, bacteria, Peptides, Immunologic Memory, Ex vivo
Abstract

Identification of protective T cell responses against SARS-CoV-2 requires distinguishing people infected with SARS-CoV-2 from those with cross-reactive immunity to other coronaviruses. Here we show a range of T cell assays that differentially capture immune function to characterise SARS-CoV-2 responses. Strong ex vivo ELISpot and proliferation responses to multiple antigens (including M, NP and ORF3) are found in 168 PCR-confirmed SARS-CoV-2 infected volunteers, but are rare in 119 uninfected volunteers. Highly exposed seronegative healthcare workers with recent COVID-19-compatible illness show T cell response patterns characteristic of infection. By contrast, >90% of convalescent or unexposed people show proliferation and cellular lactate responses to spike subunits S1/S2, indicating pre-existing cross-reactive T cell populations. The detection of T cell responses to SARS-CoV-2 is therefore critically dependent on assay and antigen selection. Memory responses to specific non-spike proteins provide a method to distinguish recent infection from pre-existing immunity in exposed populations., Understanding the immune response to SARS-CoV-2 is dependent on being able to distinguish COVID-19 immune responses from cross-reactive immune responses to other coronaviruses. Here the authors show that choice of antigens and whether an ICS, ELISPOT or T cell proliferation assay is used has a major effect on this discriminatory ability.

Published
2020

40. Natural and vaccine-induced antibody and cellular responses against emerging SARS-CoV-2 variants of concern

Author

Skelly, Donal T., primary, Harding, Adam C., additional, Gilbert-Jaramillo, Javier, additional, Knight, Michael L., additional, Longet, Stephanie, additional, Brown, Anthony, additional, Adele, Sandra, additional, Adland, Emily, additional, Brown, Helen, additional, Team, Medawar Laboratory, additional, Tipton, Tom, additional, Stafford, Lizzie, additional, Johnson, Síle A., additional, Amini, Ali, additional, Group, OPTIC Clinical, additional, Tan, Tiong Kit, additional, Schimanski, Lisa, additional, Huang, Kuan-Ying A., additional, Rijal, Pramila, additional, Group, PITCH Study, additional, Oxford, University of, additional, Frater, John, additional, Goulder, Philip, additional, Conlon, Chris, additional, Jeffery, Katie, additional, Dold, Christina, additional, Pollard, Andrew J., additional, Townsend, Alain R., additional, Klenerman, Paul, additional, Dunachie, Susanna J., additional, Barnes, Eleanor, additional, Carroll, Miles W., additional, and James, William, additional

Published
2021
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41. T-Cell and Antibody Responses to First BNT162b2 Vaccine Dose in Previously SARS-CoV-2-Infected and Infection-Naive UK Healthcare Workers: A Multicentre, Prospective, Observational Cohort Study

Author

Angyal, Adrienn, primary, Longet, Stephanie, additional, Moore, Shona, additional, Payne, Rebecca P., additional, Harding, Adam, additional, Tipton, Tom, additional, Rongkard, Patpong, additional, Ali, Mohammad, additional, Hering, Luisa M., additional, Meardon, Naomi, additional, Austin, James, additional, Brown, Rebecca, additional, Skelly, Donal, additional, Gillson, Natalie, additional, Dobson, Sue L., additional, Cross, Andrew, additional, Sandhar, Gurjinder, additional, Kilby, Jonathan A., additional, Tyerman, Jessica K., additional, Nicols, Alexander R., additional, Spegarova, Jarmila S., additional, Mehta, Hema, additional, Hornsby, Hailey, additional, Whitham, Rachel, additional, Conlon, Christopher P., additional, Jeffery, Katie, additional, Goulder, Philip, additional, Frater, John, additional, Dold, Christina, additional, Pace, Matthew, additional, Ogbe, Ane, additional, Brown, Helen, additional, Ansari, Azim M., additional, Adland, Emily, additional, Brown, Anthony, additional, Chand, Meera A., additional, Shields, Adrian, additional, Matthews, Philippa, additional, Hopkins, Susan, additional, Hall, Victoria Jane, additional, James, William, additional, Rowland-Jones, Sarah L., additional, Klenerman, Paul, additional, Dunachie, Susanna, additional, Richter, Alex G., additional, Duncan, Christopher J. A., additional, Barnes, Eleanor, additional, Carroll, Miles W., additional, Turtle, Lance, additional, de Silva, Thushan I., additional, and Consortium, PITCH, additional

Published
2021
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42. Safety and Immunogenicity of the ChAdox1 nCoV-19 (AZD1222) Vaccine Against SARS-CoV-2 in HIV Infection

Author

Frater, John, primary, Ewer, Katie, additional, Ogbe, Ane, additional, Pace, Matthew, additional, Adele, Sandra, additional, Adland, Emily, additional, Alagaratnam, Jasmini, additional, Aley, Parvinder K., additional, Ali, Mohammad, additional, Ansari, M. Azim, additional, Bara, Anna, additional, Bittaye, Mustapha, additional, Broadhead, Sam, additional, Brown, Anthony, additional, Brown, Helen, additional, Cappuccini, Federica, additional, Cooney, Enya, additional, Dejnirattisai, Wanwisa, additional, Dold, Christina, additional, Fairhead, Cassandra, additional, Fok, Henry, additional, Folegatti, Pedro M., additional, Fowler, Jamie, additional, Gibbs, Charlotte, additional, Goodman, Anna L., additional, Jenkin, Daniel, additional, Jones, Mathew, additional, Makinson, Rebecca, additional, Marchevsky, Natalie G., additional, Farooq Mujadidi, Yama, additional, Nguyen, Hanna, additional, Parolini, Lucia, additional, Petersen, Claire, additional, Plested, Emma, additional, Pollock, Katrina M., additional, Ramasamy, Maheshi N., additional, Rhead, Sarah, additional, Robinson, Hannah, additional, Robinson, Nicola, additional, Rongkard, Patpong, additional, Ryan, Fiona, additional, Serrano, Sonia, additional, Stockmann, Helen, additional, Tipoe, Timothy, additional, Voysey, Merryn, additional, Waters, Anele, additional, Zacharopoulou, Panagiota, additional, Barnes, Eleanor, additional, Dunachie, Susanna, additional, Goulder, Philip, additional, Klenerman, Paul, additional, Screaton, Gavin, additional, Winston, Alan, additional, Hill, Adrian V. S., additional, Gilbert, Sarah C., additional, Pollard, Andrew, additional, Fidler, Sarah, additional, Fox, Julie, additional, Lambe, Teresa, additional, and Group, Oxford COVID Vaccine Trial, additional

Published
2021
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44. Differential Pathogen-Specific Immune Reconstitution in Antiretroviral Therapy-Treated Human Immunodeficiency Virus-Infected Children

Author

Muenchhoff, Maximilian, Adland, Emily, Roider, Julia, Kløverpris, Henrik, Leslie, Alasdair, Boehm, Stephan, Keppler, Oliver T, Ndung’u, Thumbi, and Goulder, Philip J R

Subjects
Pathogenesis and Host Response, CD4-Positive T-Lymphocytes, Male, Programmed Cell Death 1 Receptor, antiretroviral therapy, Cytomegalovirus, HIV Infections, CD8-Positive T-Lymphocytes, Lymphocyte Activation, Major Articles and Brief Reports, Immune Reconstitution, Antiretroviral Therapy, Highly Active, Humans, Prospective Studies, Child, cytomegalovirus, Cell Proliferation, HIV, Mycobacterium tuberculosis, Phenotype, Anti-Retroviral Agents, tuberculosis, Child, Preschool, HIV-1, Cytokines, Female, Immunologic Memory
Abstract

Background Susceptibility to coinfections in human immunodeficiency virus (HIV)-infected patients remains increased despite antiretroviral therapy (ART). To elucidate mechanisms involved in immune reconstitution, we studied immune activation, immune exhaustion, and HIV- and copathogen-specific T-cell responses in children before and after ART. Methods We prospectively enrolled 25 HIV-infected children to study HIV-, cytomegalovirus (CMV)-, and tuberculosis (TB)-specific T-cell responses before and 1 year after initiation of ART using intracellular cytokine (interleukin-2, interferon-γ, tumor necrosis factor-α) staining assays after in vitro stimulation. We further measured expression of activation, immune exhaustion, and memory phenotype markers and studied proliferative responses after antigen stimulation. Results We observed differential, pathogen-specific changes after 1 year of ART in cytokine profiles of CD4 T-cell responses that were associated with shifts in memory phenotype and decreased programmed cell death 1 (PD-1) expression. The proliferative capacity of HIV- and PPD-specific responses increased after 1 year of ART. Of note, the recovery of CMV- and TB-specific responses was correlated with a decrease in PD-1 expression (r = 0.83, P = .008 and r = 0.81, P = .0007, respectively). Conclusions Reconstitution of immune responses on ART is associated with alterations in T-cell phenotype, function, and PD-1 expression that are distinct for HIV, TB, and CMV. The PD-1 pathway represents a potential target for immunotherapy in HIV-infected patients on ART with insufficient immune reconstitution., Immune activation, immune exhaustion, and T-cell responses were studied in HIV-infected children before and after 1 year of ART. Changes in T-cell functionality were observed that differed by pathogen-specificity and were correlated with alterations of PD-1 expression and memory phenotype.

Published
2019

45. Increased regulatory T-cell activity and enhanced T-cell homeostatic signaling in slow progressing HIV-infected children

Author

Roider, Julia, Ngoepe, Abigail, Muenchhoff, Maximilian, Adland, Emily, Groll, Andreas, Ndung'u, Thumbi, Kløverpris, Henrik, Goulder, Philip, Leslie, Alasdair, Roider, Julia, Ngoepe, Abigail, Muenchhoff, Maximilian, Adland, Emily, Groll, Andreas, Ndung'u, Thumbi, Kløverpris, Henrik, Goulder, Philip, and Leslie, Alasdair

Abstract

Pediatric slow progressors (PSP) are rare ART-naïve, HIV-infected children who maintain high CD4 T-cell counts and low immune activation despite persistently high viral loads. Using a well-defined cohort of PSP, we investigated the role of regulatory T-cells (TREG) and of IL-7 homeostatic signaling in maintaining normal-for-age CD4 counts in these individuals. Compared to children with progressive disease, PSP had greater absolute numbers of TREG, skewed toward functionally suppressive phenotypes. As with immune activation, overall T-cell proliferation was lower in PSP, but was uniquely higher in central memory TREG (CM TREG), indicating active engagement of this subset. Furthermore, PSP secreted higher levels of the immunosuppressive cytokine IL-10 than children who progressed. The frequency of suppressive TREG, CM TREG proliferation, and IL-10 production were all lower in PSP who go on to progress at a later time-point, supporting the importance of an active TREG response in preventing disease progression. In addition, we find that IL-7 homeostatic signaling is enhanced in PSP, both through preserved surface IL-7receptor (CD127) expression on central memory T-cells and increased plasma levels of soluble IL-7receptor, which enhances the bioactivity of IL-7. Combined analysis, using a LASSO modeling approach, indicates that both TREG activity and homeostatic T-cell signaling make independent contributions to the preservation of CD4 T-cells in HIV-infected children. Together, these data demonstrate that maintenance of normal-for-age CD4 counts in PSP is an active process, which requires both suppression of immune activation through functional TREG, and enhanced T-cell homeostatic signaling.

Published
2019

46. Plasma IL-5 but not CXCL13 correlates with neutralization breadth in HIV-infected children

Author

Roider, Julia, Zachary Porterfield, J., Ogongo, Paul, Muenchhoff, Maximilian, Adland, Emily, Groll, Andreas, Morris, Lynn, Moore, Penny L., Ndung'U, Thumbi, Kløverpris, Henrik, Goulder, Philip J.R., Leslie, Alasdair, Roider, Julia, Zachary Porterfield, J., Ogongo, Paul, Muenchhoff, Maximilian, Adland, Emily, Groll, Andreas, Morris, Lynn, Moore, Penny L., Ndung'U, Thumbi, Kløverpris, Henrik, Goulder, Philip J.R., and Leslie, Alasdair

Abstract

Children may be the optimal target for HIV vaccine development as they generate substantially more frequent and more potent broadly HIV neutralizing antibodies (bnAbs) than adults. Development of a biomarker that correlates with neutralization breadth in this group could function as a powerful tool to facilitate the development of an HIV vaccine. Previously, we observed that this preferential ability in HIV-infected children over adults to generate bnAbs is associated with an enrichment of circulating follicular helper T-cells (TFH) with an effector phenotype, and the presence of IL-21 secreting HIV-specific TFH within lymphoid tissue germinal centers (GC). In adults, bnAbs development has been linked with high plasma levels of CXCL13, a chemoattractant for CXCR5-expressing TFH cells to the lymph node GC. We sought to test this relationship in HIV-infected children, but found no association between neutralization breadth and plasma levels of CXCL13, or with the Th2 cytokines IL-4 and IL-13, or the TFH associated factor Activin A. However, we did find an unexpected association between plasma IL-5 levels and bnAb development in these children. Importantly, although CXCL13 correlated with total circulating TFH cells, it was not associated with effector TFH. Additionally, raised CXCL13 expression was associated with a lower CD4 percentage, higher viral load and a loss of immune function, implying it is associated with progressive disease rather than HIV-specific GC activity in these subjects. Taken together, our data suggests that IL-5 should be evaluated further as a candidate plasma biomarker for HIV neutralization breadth and for monitoring vaccine responses in the pediatric age group.

Published
2019

47. An HLA-I signature favouring KIR-educated Natural Killer cells mediates immune control of HIV in children and contrasts with the HLA-B-restricted CD8+ T-cell-mediated immune control in adults.

Author

Adriano Vieira, Vinicius, Adland, Emily, Malone, David F. G., Martin, Maureen P., Groll, Andreas, Ansari, M. Azim, Garcia-Guerrero, Maria C., Puertas, Mari C., Muenchhoff, Maximilian, Guash, Claudia Fortuny, Brander, Christian, Martinez-Picado, Javier, Bamford, Alasdair, Tudor-Williams, Gareth, Ndung'u, Thumbi, Walker, Bruce D., Ramsuran, Veron, Frater, John, Jooste, Pieter, and Peppa, Dimitra

Subjects
*ADULTS, *HIV-positive children, *CD8 antigen, *IMMUNE response, *CELL populations, *KILLER cells, *AGE groups
Abstract

Natural Killer (NK) cells contribute to HIV control in adults, but HLA-B-mediated T-cell activity has a more substantial impact on disease outcome. However, the HLA-B molecules influencing immune control in adults have less impact on paediatric infection. To investigate the contribution NK cells make to immune control, we studied >300 children living with HIV followed over two decades in South Africa. In children, HLA-B alleles associated with adult protection or disease-susceptibility did not have significant effects, whereas Bw4 (p = 0.003) and low HLA-A expression (p = 0.002) alleles were strongly associated with immunological and viral control. In a comparator adult cohort, Bw4 and HLA-A expression contributions to HIV disease outcome were dwarfed by those of protective and disease-susceptible HLA-B molecules. We next investigated the immunophenotype and effector functions of NK cells in a subset of these children using flow cytometry. Slow progression and better plasma viraemic control were also associated with high frequencies of less terminally differentiated NKG2A+NKp46+CD56dim NK cells strongly responsive to cytokine stimulation and linked with the immunogenetic signature identified. Future studies are indicated to determine whether this signature associated with immune control in early life directly facilitates functional cure in children. Author summary: In adults, immune control of HIV is strongly influenced by antiviral CD8+ T-cell responses restricted by 'protective' HLA class I molecules, such as HLA-B*57, and by 'disease-susceptible' HLA class I molecules such as HLA-B*58:02. By contrast, Natural Killer (NK) cells responses make a smaller, albeit significant, contribution. In this study, we evaluate in children living with HIV the contribution of NK cell responses to immune control of HIV, in an age group where HIV-specific CD8+ T-cell responses have less impact on disease outcome. A cohort of >300 therapy-naïve children living with HIV shows that a genetic signature favouring a KIR-education on NK cells is associated with slow progression and better viraemic control. Consistent with this, we observed control of HIV viraemia and lower total HIV DNA levels among children was associated with a less differentiated NKG2A+NKp46+ CD56dim NK cell population that functionally was highly responsive to cytokine stimulation. Thus, the study identifies a signature that can impact future therapeutic strategies to achieve remission in children. [ABSTRACT FROM AUTHOR]

Published
2021
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48. Plasma IL-5 but Not CXCL13 Correlates With Neutralization Breadth in HIV-Infected Children

Author

Roider, Julia, primary, Porterfield, J. Zachary, additional, Ogongo, Paul, additional, Muenchhoff, Maximilian, additional, Adland, Emily, additional, Groll, Andreas, additional, Morris, Lynn, additional, Moore, Penny L., additional, Ndung'u, Thumbi, additional, Kløverpris, Henrik, additional, Goulder, Philip J. R., additional, and Leslie, Alasdair, additional

Published
2019
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