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1. Omicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history

Author

Hornsby, Hailey, Nicols, Alexander R., Longet, Stephanie, Liu, Chang, Tomic, Adriana, Angyal, Adrienn, Kronsteiner, Barbara, Tyerman, Jessica K., Tipton, Tom, Zhang, Peijun, Gallis, Marta, Supasa, Piyada, Selvaraj, Muneeswaran, Abraham, Priyanka, Neale, Isabel, Ali, Mohammad, Barratt, Natalie A., Nell, Jeremy M., Gustafsson, Lotta, Strickland, Scarlett, Grouneva, Irina, Rostron, Timothy, Moore, Shona C., Hering, Luisa M., Dobson, Susan L., Bibi, Sagida, Mongkolsapaya, Juthathip, Lambe, Teresa, Wootton, Dan, Hall, Victoria, Hopkins, Susan, Dong, Tao, Barnes, Eleanor, Screaton, Gavin, Richter, Alex, Turtle, Lance, Rowland-Jones, Sarah L., Carroll, Miles, Duncan, Christopher J. A., Klenerman, Paul, Dunachie, Susanna J., Payne, Rebecca P., and de Silva, Thushan I.

Published
2023
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2. Evaluation of T cell responses to naturally processed variant SARS-CoV-2 spike antigens in individuals following infection or vaccination

Author

Yin, Zixi, Chen, Ji-Li, Lu, Yongxu, Wang, Beibei, Godfrey, Leila, Mentzer, Alexander J., Yao, Xuan, Liu, Guihai, Wellington, Dannielle, Zhao, Yiqi, Wing, Peter A.C., Dejnirattisa, Wanwisa, Supasa, Piyada, Liu, Chang, Hublitz, Philip, Beveridge, Ryan, Waugh, Craig, Clark, Sally-Ann, Clark, Kevin, Sopp, Paul, Rostron, Timothy, Mongkolsapaya, Juthathip, Screaton, Gavin R., Ogg, Graham, Ewer, Katie, Pollard, Andrew J., Gilbert, Sarah, Knight, Julian C., Lambe, Teresa, Smith, Geoffrey L., Dong, Tao, and Peng, Yanchun

Published
2023
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3. An immunodominant NP105–113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease

Author

Peng, Yanchun, Felce, Suet Ling, Dong, Danning, Penkava, Frank, Mentzer, Alexander J., Yao, Xuan, Liu, Guihai, Yin, Zixi, Chen, Ji-Li, Lu, Yongxu, Wellington, Dannielle, Wing, Peter A. C., Dominey-Foy, Delaney C. C., Jin, Chen, Wang, Wenbo, Hamid, Megat Abd, Fernandes, Ricardo A., Wang, Beibei, Fries, Anastasia, Zhuang, Xiaodong, Ashley, Neil, Rostron, Timothy, Waugh, Craig, Sopp, Paul, Hublitz, Philip, Beveridge, Ryan, Tan, Tiong Kit, Dold, Christina, Kwok, Andrew J., Rich-Griffin, Charlotte, Dejnirattisa, Wanwisa, Liu, Chang, Kurupati, Prathiba, Nassiri, Isar, Watson, Robert A., Tong, Orion, Taylor, Chelsea A., Kumar Sharma, Piyush, Sun, Bo, Curion, Fabiola, Revale, Santiago, Garner, Lucy C., Jansen, Kathrin, Ferreira, Ricardo C., Attar, Moustafa, Fry, Jeremy W., Russell, Rebecca A., Stauss, Hans J., James, William, Townsend, Alain, Ho, Ling-Pei, Klenerman, Paul, Mongkolsapaya, Juthathip, Screaton, Gavin R., Dendrou, Calliope, Sansom, Stephen N., Bashford-Rogers, Rachael, Chain, Benny, Smith, Geoffrey L., McKeating, Jane A., Fairfax, Benjamin P., Bowness, Paul, McMichael, Andrew J., Ogg, Graham, Knight, Julian C., and Dong, Tao

Published
2022
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4. Omicron BA.1/BA.2 infections in triple-vaccinated individuals enhance a diverse repertoire of mucosal and blood immune responses

Author

Hornsby, Hailey, primary, Nicols, Alexander R., additional, Longet, Stephanie, additional, Liu, Chang, additional, Tomic, Adriana, additional, Angyal, Adrienn, additional, Kronsteiner, Barbara, additional, Tyerman, Jessica K., additional, Tipton, Tom, additional, Zhang, Peijun, additional, Ramalho, Marta Gallis, additional, Supasa, Piyada, additional, Selvaraj, Muneeswaran, additional, Abraham, Priyanka, additional, Neale, Isabel, additional, Ali, Mohammad, additional, Barratt, Natalie A., additional, Nell, Jeremy M., additional, Gustafsson, Lotta, additional, Strickland, Scarlett, additional, Grouneva, Irina, additional, Rostron, Timothy, additional, Moore, Shona C., additional, Hering, Luisa M., additional, Dobson, Susan L., additional, Bibi, Sagida, additional, Mongkolsapaya, Juthathip, additional, Lambe, Teresa, additional, Wootton, Dan, additional, Hall, Victoria, additional, Hopkins, Susan, additional, Dong, Tao, additional, Barnes, Eleanor, additional, Screaton, Gavin, additional, Richter, Alex, additional, Turtle, Lance, additional, Rowland-Jones, Sarah L., additional, Carroll, Miles, additional, Duncan, Christopher J.A., additional, Klenerman, Paul, additional, Dunachie, Susanna J., additional, Payne, Rebecca P., additional, and de Silva, Thushan I., additional

Published
2023
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5. Evaluation of T Cell Responses to Naturally Processed Variant SARS-CoV-2 Spike Antigens in Individuals Following Infection or Vaccination

Author

Yin, Zixi, primary, Chen, Ji-Li, additional, Lu, Yongxu, additional, Wang, Beibei, additional, Godfrey, Leila, additional, Mentzer, Alexander J., additional, Yao, Xuan, additional, Liu, Guihai, additional, Wellington, Dannielle, additional, Zhong, Qi, additional, Wing, Peter AC, additional, Dejnirattisai, Wanwisa, additional, Supasa, Piyada, additional, Liu, Chang, additional, Hublitz, Philip, additional, Beveridge, Ryan, additional, Waugh, Craig, additional, Clark, Sally-Ann, additional, Clark, Kevin, additional, Sopp, Paul, additional, Rostron, Timothy, additional, Mongkolspaya, Juthathip, additional, Screaton, Gavin R., additional, Ogg, Graham S., additional, Pollard, Andrew J., additional, Gilbert, Sarah C., additional, Knight, Julian, additional, Lambe, Teresa, additional, Smith, Geoffrey, additional, Dong, Tao, additional, and Peng, Yanchun, additional

Published
2023
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6. Memory cytotoxic SARS-CoV-2 spike protein-specific CD4+ T cells associate with viral control

Author

Dong, Tao, primary, Liu, Guihai, additional, Felce, Suet, additional, Yao, Xuan, additional, Yin, Zixi, additional, Fries, Anastasia, additional, Mentzer, Alexander, additional, Dong, Danning, additional, Wang, Wenbo, additional, Dejnirattisai, Wanwisa, additional, Supasa, Piyada, additional, Liu, Chang, additional, Wing, Peter, additional, Rostron, Timothy, additional, Waugh, Craig, additional, Clark, Sally-Ann, additional, Clark, Kevin, additional, Sopp, Paul, additional, Hublitz, Philip, additional, Beveridge, Ryan, additional, Fry, Jeremy, additional, McKeating, Jane, additional, Mongkolsapaya, Juthathip, additional, Screaton, Gavin, additional, Ogg, Graham, additional, Knight, Julian, additional, and Peng, Yanchun, additional

Published
2022
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7. Immunodominant NP105-113-B*0702 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease

Author

Dong, Tao, primary, Ogg, Graham, additional, Peng, Yan-Chun, additional, Felce, Suet, additional, Dong, Danning, additional, Penkava, Frank, additional, Mentzer, Alexander, additional, Lao, Xuan, additional, Liu, Guihai, additional, Yin, Zixi, additional, Chen, Ji-Li, additional, Lu, YongXu, additional, Wellington, Dannielle, additional, Wing, Peter, additional, Dominey-Foy, Delaney, additional, Knight, Julian, additional, Jin, Chen, additional, Wang, Wenbo, additional, Hamid, Megat Abd, additional, Fernandes, Ricardo, additional, Wang, Beibei, additional, Fries, Anastasia, additional, Zhuang, Xiaodong, additional, Ashley, Neil, additional, Rostron, Timothy, additional, Waugh, Craig, additional, Sopp, Paul, additional, Hublitz, Philip, additional, Beveridge, Ryan, additional, Tan, Tiong Kit, additional, Dold, Christina, additional, Kwok, Andrew, additional, Rich-Griffin, Charlotte, additional, Dejnirattisai, Wanwisa, additional, Nassiri, Isar, additional, Watson, Robert, additional, Tong, Orion, additional, Taylor, Chelsea, additional, Sharma, Piyush Kumar, additional, Curion, Fabiola, additional, Revale, Santiago, additional, Garner, Lucy, additional, Jansen, Kathrin, additional, Ferreira, Ricardo, additional, Attar, Moustafa, additional, Fry, Jeremy, additional, Russell, Rebecca, additional, Stauss, Hans, additional, James, William, additional, Townsend, Alain, additional, Ho, Ling-Pei, additional, Mongkolsapaya, Juthathip, additional, Klenerman, Paul, additional, Screaton, Gavin, additional, Dendrou, Calliope, additional, Sansom, Stephen, additional, Bashford-Rogers, Rachael, additional, Chain, Benny, additional, Smith, Geoffrey, additional, McKeating, Jane, additional, Fairfax, Benjamin, additional, Bowness, Paul, additional, and McMichael, Andrew, additional

Published
2021
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13. Broad and strong memory CD4+and CD8+T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19

Author

Peng, Yanchun, Mentzer, Alexander J., Liu, Guihai, Yao, Xuan, Yin, Zixi, Dong, Danning, Dejnirattisai, Wanwisa, Rostron, Timothy, Supasa, Piyada, Liu, Chang, López-Camacho, César, Slon-Campos, Jose, Zhao, Yuguang, Stuart, David I., Paesen, Guido C., Grimes, Jonathan M., Antson, Alfred A., Bayfield, Oliver W., Hawkins, Dorothy E. D. P., Ker, De-Sheng, Wang, Beibei, Turtle, Lance, Subramaniam, Krishanthi, Thomson, Paul, Zhang, Ping, Dold, Christina, Ratcliff, Jeremy, Simmonds, Peter, de Silva, Thushan, Sopp, Paul, Wellington, Dannielle, Rajapaksa, Ushani, Chen, Yi-Ling, Salio, Mariolina, Napolitani, Giorgio, Paes, Wayne, Borrow, Persephone, Kessler, Benedikt M., Fry, Jeremy W., Schwabe, Nikolai F., Semple, Malcolm G., Baillie, J. Kenneth, Moore, Shona C., Openshaw, Peter J. M., Ansari, M. Azim, Dunachie, Susanna, Barnes, Eleanor, Frater, John, Kerr, Georgina, Goulder, Philip, Lockett, Teresa, Levin, Robert, Zhang, Yonghong, Jing, Ronghua, Ho, Ling-Pei, Cornall, Richard J., Conlon, Christopher P., Klenerman, Paul, Screaton, Gavin R., Mongkolsapaya, Juthathip, McMichael, Andrew, Knight, Julian C., Ogg, Graham, and Dong, Tao

Abstract

The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-γ-based assays with peptides spanning SARS-CoV-2 except ORF1. The breadth and magnitude of T cell responses were significantly higher in severe as compared with mild cases. Total and spike-specific T cell responses correlated with spike-specific antibody responses. We identified 41 peptides containing CD4+and/or CD8+epitopes, including six immunodominant regions. Six optimized CD8+epitopes were defined, with peptide–MHC pentamer-positive cells displaying the central and effector memory phenotype. In mild cases, higher proportions of SARS-CoV-2-specific CD8+T cells were observed. The identification of T cell responses associated with milder disease will support an understanding of protective immunity and highlights the potential of including non-spike proteins within future COVID-19 vaccine design.

Published
2020
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14. Human Leukocyte Antigen (HLA) B*18 and Protection against Mother-to-Child HIV Type 1 Transmission

Author

Farquhar, Carey, primary, Rowland-Jones, Sarah, additional, Mbori-Ngacha, Dorothy, additional, Redman, Mary, additional, Lohman, Barbara, additional, Slyker, Jennifer, additional, Otieno, Phelgona, additional, Obimbo, Elizabeth, additional, Rostron, Timothy, additional, Ochieng, James, additional, Oyugi, Julius, additional, Bosire, Rose, additional, and John-Stewart, Grace, additional

Published
2004
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15. Association between Maternal and Infant Class I and II HLA Alleles and of Their Concordance with the Risk of Perinatal HIV Type 1 Transmission

Author

Polycarpou, Anastasia, primary, Ntais, Christos, additional, Korber, Bette T., additional, Elrich, Henry A., additional, Winchester, Robert, additional, Krogstad, Paul, additional, Wolinsky, Steven, additional, Rostron, Timothy, additional, Rowland-Jones, Sarah L., additional, Ammann, Arthur J., additional, and Ioannidis, John P.A., additional

Published
2002
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17. Maternal viral load, CD4 cell count and vertical transmission of HIV-1

Author

O'Shea, Siobhan, primary, Newell, Marie-Louise, additional, Dunn, David T., additional, Garcia-Rodriguez, Marie-Cruz, additional, Bates, Isabel, additional, Mullen, Jane, additional, Rostron, Timothy, additional, Corbett, Karen, additional, Aiyer, Swati, additional, Butler, Karina, additional, Smith, Robert, additional, and Banatvala, Jangu E., additional

Published
1998
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20. Broad and strong memory CD4 + and CD8 + T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19.

Author

Peng Y, Mentzer AJ, Liu G, Yao X, Yin Z, Dong D, Dejnirattisai W, Rostron T, Supasa P, Liu C, López-Camacho C, Slon-Campos J, Zhao Y, Stuart DI, Paesen GC, Grimes JM, Antson AA, Bayfield OW, Hawkins DEDP, Ker DS, Wang B, Turtle L, Subramaniam K, Thomson P, Zhang P, Dold C, Ratcliff J, Simmonds P, de Silva T, Sopp P, Wellington D, Rajapaksa U, Chen YL, Salio M, Napolitani G, Paes W, Borrow P, Kessler BM, Fry JW, Schwabe NF, Semple MG, Baillie JK, Moore SC, Openshaw PJM, Ansari MA, Dunachie S, Barnes E, Frater J, Kerr G, Goulder P, Lockett T, Levin R, Zhang Y, Jing R, Ho LP, Cornall RJ, Conlon CP, Klenerman P, Screaton GR, Mongkolsapaya J, McMichael A, Knight JC, Ogg G, and Dong T

Subjects
COVID-19, COVID-19 Vaccines, Coronavirus Infections immunology, Coronavirus Infections pathology, Coronavirus Infections prevention & control, Epitopes, T-Lymphocyte immunology, Humans, Immunodominant Epitopes immunology, Pandemics, Pneumonia, Viral immunology, Pneumonia, Viral pathology, SARS-CoV-2, Spike Glycoprotein, Coronavirus immunology, United Kingdom, Viral Vaccines immunology, Antigens, Viral immunology, Betacoronavirus immunology, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Immunologic Memory immunology
Abstract

The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-γ-based assays with peptides spanning SARS-CoV-2 except ORF1. The breadth and magnitude of T cell responses were significantly higher in severe as compared with mild cases. Total and spike-specific T cell responses correlated with spike-specific antibody responses. We identified 41 peptides containing CD4 + and/or CD8 + epitopes, including six immunodominant regions. Six optimized CD8 + epitopes were defined, with peptide-MHC pentamer-positive cells displaying the central and effector memory phenotype. In mild cases, higher proportions of SARS-CoV-2-specific CD8 + T cells were observed. The identification of T cell responses associated with milder disease will support an understanding of protective immunity and highlights the potential of including non-spike proteins within future COVID-19 vaccine design.

Published
2020
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21. Broad and strong memory CD4 + and CD8 + T cells induced by SARS-CoV-2 in UK convalescent COVID-19 patients.

Author

Peng Y, Mentzer AJ, Liu G, Yao X, Yin Z, Dong D, Dejnirattisai W, Rostron T, Supasa P, Liu C, Lopez-Camacho C, Slon-Campos J, Zhao Y, Stuart D, Paeson G, Grimes J, Antson F, Bayfield OW, Hawkins DE, Ker DS, Turtle L, Subramaniam K, Thomson P, Zhang P, Dold C, Ratcliff J, Simmonds P, de Silva T, Sopp P, Wellington D, Rajapaksa U, Chen YL, Salio M, Napolitani G, Paes W, Borrow P, Kessler B, Fry JW, Schwabe NF, Semple MG, Baillie KJ, Moore S, Openshaw PJ, Ansari A, Dunachie S, Barnes E, Frater J, Kerr G, Goulder P, Lockett T, Levin R, Cornall RJ, Conlon C, Klenerman P, McMichael A, Screaton G, Mongkolsapaya J, Knight JC, Ogg G, and Dong T

Abstract

COVID-19 is an ongoing global crisis in which the development of effective vaccines and therapeutics will depend critically on understanding the natural immunity to the virus, including the role of SARS-CoV-2-specific T cells. We have conducted a study of 42 patients following recovery from COVID-19, including 28 mild and 14 severe cases, comparing their T cell responses to those of 16 control donors. We assessed the immune memory of T cell responses using IFNγ based assays with overlapping peptides spanning SARS-CoV-2 apart from ORF1. We found the breadth, magnitude and frequency of memory T cell responses from COVID-19 were significantly higher in severe compared to mild COVID-19 cases, and this effect was most marked in response to spike, membrane, and ORF3a proteins. Total and spike-specific T cell responses correlated with the anti-Spike, anti-Receptor Binding Domain (RBD) as well as anti-Nucleoprotein (NP) endpoint antibody titre (p<0.001, <0.001 and =0.002). We identified 39 separate peptides containing CD4 + and/or CD8 + epitopes, which strikingly included six immunodominant epitope clusters targeted by T cells in many donors, including 3 clusters in spike (recognised by 29%, 24%, 18% donors), two in the membrane protein (M, 32%, 47%) and one in the nucleoprotein (Np, 35%). CD8+ responses were further defined for their HLA restriction, including B*4001-restricted T cells showing central memory and effector memory phenotype. In mild cases, higher frequencies of multi-cytokine producing M- and NP-specific CD8 + T cells than spike-specific CD8 + T cells were observed. They furthermore showed a higher ratio of SARS-CoV-2-specific CD8 + to CD4 + T cell responses. Immunodominant epitope clusters and peptides containing T cell epitopes identified in this study will provide critical tools to study the role of virus-specific T cells in control and resolution of SARS-CoV-2 infections. The identification of T cell specificity and functionality associated with milder disease, highlights the potential importance of including non-spike proteins within future COVID-19 vaccine design.

Published
2020
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22. Defective Interferon Gamma Production by Tumor-Specific CD8 + T Cells Is Associated With 5'Methylcytosine-Guanine Hypermethylation of Interferon Gamma Promoter.

Author

Abd Hamid M, Yao X, Waugh C, Rosendo-Machado S, Li C, Rostron T, Frankland J, Peng Y, and Dong T

Subjects
Humans, Interferon-gamma genetics, Promoter Regions, Genetic, Antigens, Neoplasm immunology, CD8-Positive T-Lymphocytes immunology, CpG Islands genetics, DNA Methylation, Interferon-gamma biosynthesis
Abstract

Interferon gamma (IFNγ) supports effector responses of CD8 + cytotoxic T lymphocytes (CTLs) and is a surrogate marker for detection of antigen-specific T cells. Here, we show that tumor-specific CTL clones have impaired IFNγ expression and production upon activation. Assessment of the relationship between IFNγ production and the 5'methylcytosine-guanine (CpG) dinucleotide methylation of the IFNγ promoter using bisulfite treatment has shown that IFNγ - CTL clones accumulates CpG hypermethylation within the promoter at key transcription factor binding sites (-186 and -54), known to be vital for transcription. We confirmed these findings using ex vivo isolated and short-term expanded bulk tumor-specific CTL lines from four cancer patients and demonstrated that IFNγ methylation inversely correlates with transcription, protein level, and cytotoxicity. Altogether, we propose that a sizeable portion of human tumor-specific CTLs are deficient in IFNγ response, contributed by CpG hypermethylation of the IFNγ promoter. Our findings have important implications for immunotherapy strategies and for methods to detect human antigen-specific T cells., (Copyright © 2020 Abd Hamid, Yao, Waugh, Rosendo-Machado, Li, Rostron, Frankland, Peng and Dong.)

Published
2020
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