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1. Immunogenicity of third dose COVID-19 vaccine strategies in patients who are immunocompromised with suboptimal immunity following two doses (OCTAVE-DUO): an open-label, multicentre, randomised, controlled, phase 3 trial

Author

Beesley, Richard, Churchill, Vicky, Insch, Elspeth, Loughton, Holly, MacDonald, Eilean, Lax, Siân, Lowe, Faye, Magwaro, Sophia, Gradwell, Mark, Kinsella, Francesca, Rolfe, Hayley, McIntyre, Stacey, Mortimer, Paige, Al-Taei, Saly, Tadros, Susan, Workman, Sarita, Arnott, Maxine, Brock, James, Melville, Andrew, Najm, Aurelie, Rutherford, Matthew, Sunzini, Flavia, Herman, Lou S, Hobbs, Agnieszka, Ragno, Martina, Wu, Mary Y, Selby, Rachael, Clay, Jennifer, Hutchison, Clare, Lown, Robert, Lwin, May N, Meardon, Naomi, Kelleher, Peter, Lightstone, Liz, Walters, Thomas, Denyer, Jayne, Ibrahim, Rahima, Gleeson, Sarah, Martin, Paul, McAdoo, Stephen, Baker, Helena, Horswill, Sarah, Parungao, Nina, Saich, Stephen, Cullinane, James, Irwin, Sophie, Klenerman, Paul, Marjot, Thomas, Chakraverty, Ronjon, Holroyd, Christopher, Kavi, Janki, Trown, Doreen, Babbage, Gavin, Chackathayil, Julia, Faria, Patricia, Ingham, Karen, Miah, Murad, Miranda, Mauro, O'Reilly, Nicola, Smith, Callie, Driver, Kimberley, Gauntlett, Kaylee, Farthing, Andrew, Rundell, Suzann, Smith, Emily, Tong, Andrew, Woolcock, Kieran, Hanke, Daniel, Laidlaw, Stephen, Malik, Zainab, Nguyen, Dung, Provine, Nicholas, Tipton, Tom, Walker, Victoria, Goodyear, Carl S, Patel, Amit, Barnes, Eleanor, Willicombe, Michelle, Siebert, Stefan, de Silva, Thushan I, Snowden, John A, Lim, Sean H, Bowden, Sarah J, Billingham, Lucinda, Richter, Alex, Carroll, Miles, Carr, Edward J, Beale, Rupert, Rea, Daniel, Parry, Helen, Pirrie, Sarah, Lim, Zixiang, Satsangi, Jack, Dunachie, Susanna J, Cook, Gordon, Miller, Paul, Basu, Neil, Gilmour, Ashley, Hodgkins, Anne-Marie, Evans, Lili, Hughes, Ana, Longet, Stephanie, Meacham, Georgina, Yong, Kwee L, A'Hearne, Matthew J, Koh, Mickey B C, Burns, Siobhan O, Orchard, Kim, Paterson, Caron, McIlroy, Graham, Murray, Sam M, Thomson, Tina, Dimitriadis, Stavros, Goulston, Lyndsey, Miller, Samantha, Keillor, Victoria, Prendecki, Maria, Thomas, David, Kirkham, Amanda, McInnes, Iain B, and Kearns, Pamela

Published
2024
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2. SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease

Author

Barnes, Eleanor, Goodyear, Carl S., Willicombe, Michelle, Gaskell, Charlotte, Siebert, Stefan, I de Silva, Thushan, Murray, Sam M., Rea, Daniel, Snowden, John A., Carroll, Miles, Pirrie, Sarah, Bowden, Sarah J., Dunachie, Susanna J., Richter, Alex, Lim, Zixiang, Satsangi, Jack, Cook, Gordon, Pope, Ann, Hughes, Ana, Harrison, Molly, Lim, Sean H., Miller, Paul, Klenerman, Paul, Basu, Neil, Gilmour, Ashley, Irwin, Sophie, Meacham, Georgina, Marjot, Thomas, Dimitriadis, Stavros, Kelleher, Peter, Prendecki, Maria, Clarke, Candice, Mortimer, Paige, McIntyre, Stacey, Selby, Rachael, Meardon, Naomi, Nguyen, Dung, Tipton, Tom, Longet, Stephanie, Laidlaw, Stephen, Orchard, Kim, Ireland, Georgina, Thomas, David, Kearns, Pamela, Kirkham, Amanda, and McInnes, Iain B.

Published
2023
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3. Immune responses and clinical outcomes after COVID-19 vaccination in patients with liver disease and liver transplant recipients

Author

Murray, Sam M., Pose, Elisa, Wittner, Melanie, Londoño, Maria-Carlota, Schaub, Golda, Cook, Jonathan, Dimitriadis, Stavros, Meacham, Georgina, Irwin, Sophie, Lim, Zixiang, Duengelhoef, Paul, Sterneck, Martina, Lohse, Ansgar W., Perez, Valeria, Trivedi, Palak, Bhandal, Khush, Mullish, Benjamin H., Manousou, Pinelopi, Provine, Nicholas M., Avitabile, Emma, Carroll, Miles, Tipton, Tom, Healy, Saoirse, Burra, Patrizia, Klenerman, Paul, Dunachie, Susanna, Kronsteiner, Barbara, Maciola, Agnieszka Katarzyna, Pasqual, Giulia, Hernandez-Gea, Virginia, Garcia-Pagan, Juan Carlos, Lampertico, Pietro, Iavarone, Massimo, Gines, Pere, Lütgehetmann, Marc, Schulze zur Wiesch, Julian, Russo, Francesco Paolo, Barnes, Eleanor, and Marjot, Thomas

Published
2024
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5. Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response

Author

Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Altmann, Daniel M., Amin, Oliver E., Andiapen, Mervyn, Artico, Jessica, Augusto, João B., Baca, Georgina L., Bailey, Sasha N.L., Bhuva, Anish N., Boulter, Alex, Bowles, Ruth, Boyton, Rosemary J., Bracken, Olivia V., O’Brien, Ben, Brooks, Tim, Bullock, Natalie, Butler, David K., Captur, Gabriella, Carr, Olivia, Champion, Nicola, Chan, Carmen, Chandran, Aneesh, Coleman, Tom, Couto de Sousa, Jorge, Couto-Parada, Xose, Cross, Eleanor, Cutino-Moguel, Teresa, D’Arcangelo, Silvia, Davies, Rhodri H., Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O., Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Fontana, Marianna, Forooghi, Nasim, Francis, Sasha, Gibbons, Joseph M., Gillespie, David, Gilroy, Derek, Hamblin, Matt, Harker, Gabrielle, Hemingway, Georgia, Hewson, Jacqueline, Heywood, Wendy, Hickling, Lauren M., Hicks, Bethany, Hingorani, Aroon D., Howes, Lee, Itua, Ivie, Jardim, Victor, Lee, Wing-Yiu Jason, Jensen, Melaniepetra, Jones, Jessica, Jones, Meleri, Joy, George, Kapil, Vikas, Kelly, Caoimhe, Kurdi, Hibba, Lambourne, Jonathan, Lin, Kai-Min, Liu, Siyi, Lloyd, Aaron, Louth, Sarah, Maini, Mala K., Mandadapu, Vineela, Manisty, Charlotte, McKnight, Áine, Menacho, Katia, Mfuko, Celina, Mills, Kevin, Millward, Sebastian, Mitchelmore, Oliver, Moon, Christopher, Moon, James, Sandoval, Diana Muñoz, Murray, Sam M., Noursadeghi, Mahdad, Otter, Ashley, Pade, Corinna, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Mihaela, Petersen, Steffen E., Piniera, Brian, Pieper, Franziska P., Rannigan, Lisa, Rapala, Alicja, Reynolds, Catherine J., Richards, Amy, Robathan, Matthew, Rosenheim, Joshua, Rowe, Cathy, Royds, Matthew, West, Jane Sackville, Sambile, Genine, Schmidt, Nathalie M., Selman, Hannah, Semper, Amanda, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel, Thomas, Stephen, Thornton, George D., Treibel, Thomas A., Tucker, Art, Varghese, Ann, Veerapen, Jessry, Vijayakumar, Mohit, Warner, Tim, Welch, Sophie, White, Hannah, Wodehouse, Theresa, Wynne, Lucinda, Zahedi, Dan, Doykov, Ivan, Baldwin, Tomas, Spiewak, Justyna, Gilmour, Kimberly C., Áine McKnight, Treibel, Thomas, Moon, James C., Kevin Mills, and Heywood, Wendy E.

Published
2022
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6. Immunogenicity of third dose COVID-19 vaccine strategies in patients who are immunocompromised with suboptimal immunity following two doses (OCTAVE-DUO): an open-label, multicentre, randomised, controlled, phase 3 trial

Author

Goodyear, Carl S, primary, Patel, Amit, additional, Barnes, Eleanor, additional, Willicombe, Michelle, additional, Siebert, Stefan, additional, de Silva, Thushan I, additional, Snowden, John A, additional, Lim, Sean H, additional, Bowden, Sarah J, additional, Billingham, Lucinda, additional, Richter, Alex, additional, Carroll, Miles, additional, Carr, Edward J, additional, Beale, Rupert, additional, Rea, Daniel, additional, Parry, Helen, additional, Pirrie, Sarah, additional, Lim, Zixiang, additional, Satsangi, Jack, additional, Dunachie, Susanna J, additional, Cook, Gordon, additional, Miller, Paul, additional, Basu, Neil, additional, Gilmour, Ashley, additional, Hodgkins, Anne-Marie, additional, Evans, Lili, additional, Hughes, Ana, additional, Longet, Stephanie, additional, Meacham, Georgina, additional, Yong, Kwee L, additional, A'Hearne, Matthew J, additional, Koh, Mickey B C, additional, Burns, Siobhan O, additional, Orchard, Kim, additional, Paterson, Caron, additional, McIlroy, Graham, additional, Murray, Sam M, additional, Thomson, Tina, additional, Dimitriadis, Stavros, additional, Goulston, Lyndsey, additional, Miller, Samantha, additional, Keillor, Victoria, additional, Prendecki, Maria, additional, Thomas, David, additional, Kirkham, Amanda, additional, McInnes, Iain B, additional, Kearns, Pamela, additional, Beesley, Richard, additional, Churchill, Vicky, additional, Insch, Elspeth, additional, Loughton, Holly, additional, MacDonald, Eilean, additional, Lax, Siân, additional, Lowe, Faye, additional, Magwaro, Sophia, additional, Gradwell, Mark, additional, Kinsella, Francesca, additional, Rolfe, Hayley, additional, McIntyre, Stacey, additional, Mortimer, Paige, additional, Al-Taei, Saly, additional, Tadros, Susan, additional, Workman, Sarita, additional, Arnott, Maxine, additional, Brock, James, additional, Melville, Andrew, additional, Najm, Aurelie, additional, Rutherford, Matthew, additional, Sunzini, Flavia, additional, Herman, Lou S, additional, Hobbs, Agnieszka, additional, Ragno, Martina, additional, Wu, Mary Y, additional, Selby, Rachael, additional, Clay, Jennifer, additional, Hutchison, Clare, additional, Lown, Robert, additional, Lwin, May N, additional, Meardon, Naomi, additional, Kelleher, Peter, additional, Lightstone, Liz, additional, Walters, Thomas, additional, Denyer, Jayne, additional, Ibrahim, Rahima, additional, Gleeson, Sarah, additional, Martin, Paul, additional, McAdoo, Stephen, additional, Baker, Helena, additional, Horswill, Sarah, additional, Parungao, Nina, additional, Saich, Stephen, additional, Cullinane, James, additional, Irwin, Sophie, additional, Klenerman, Paul, additional, Marjot, Thomas, additional, Chakraverty, Ronjon, additional, Holroyd, Christopher, additional, Kavi, Janki, additional, Trown, Doreen, additional, Babbage, Gavin, additional, Chackathayil, Julia, additional, Faria, Patricia, additional, Ingham, Karen, additional, Miah, Murad, additional, Miranda, Mauro, additional, O'Reilly, Nicola, additional, Smith, Callie, additional, Driver, Kimberley, additional, Gauntlett, Kaylee, additional, Farthing, Andrew, additional, Rundell, Suzann, additional, Smith, Emily, additional, Tong, Andrew, additional, Woolcock, Kieran, additional, Hanke, Daniel, additional, Laidlaw, Stephen, additional, Malik, Zainab, additional, Nguyen, Dung, additional, Provine, Nicholas, additional, Tipton, Tom, additional, and Walker, Victoria, additional

Published
2024
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7. Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection: a nested, case-control diagnostic accuracy study

Author

Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Altmann, Daniel M, Amin, Oliver E, Andiapen, Mervyn, Artico, Jessica, Augusto, João B, Baca, Georgiana L, Bailey, Sasha NL, Bhuva, Anish N, Boulter, Alex, Bowles, Ruth, Boyton, Rosemary J, Bracken, Olivia V, O'Brien, Ben, Brooks, Tim, Bullock, Natalie, Butler, David K, Captur, Gabriella, Champion, Nicola, Chan, Carmen, Chandran, Aneesh, Collier, David, Couto de Sousa, Jorge, Couto-Parada, Xose, Cutino-Moguel, Teresa, Davies, Rhodri H, Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O, Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Fontana, Marianna, Forooghi, Nasim, Gaier, Celia, Gibbons, Joseph M, Gilroy, Derek, Hamblin, Matt, Harker, Gabrielle, Hewson, Jacqueline, Hickling, Lauren M, Hingorani, Aroon D, Howes, Lee, Hughes, Alun, Hughes, Gemma, Hughes, Rebecca, Itua, Ivie, Jardim, Victor, Lee, Wing-Yiu Jason, Jensen, Melaniepetra, Jones, Jessica, Jones, Meleri, Joy, George, Kapil, Vikas, Kurdi, Hibba, Lambourne, Jonathan, Lin, Kai-Min, Louth, Sarah, Maini, Mala K, Mandadapu, Vineela, Manisty, Charlotte, McKnight, Áine, Menacho, Katia, Mfuko, Celina, Mitchelmore, Oliver, Moon, Christopher, Moon, James C, Munoz Sandoval, Diana, Murray, Sam M, Noursadeghi, Mahdad, Otter, Ashley, Pade, Corinna, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Babita, Petersen, Steffen E, Piniera, Brian, Pieper, Franziska P, Pope, Daniel, Prossora, Maria, Rannigan, Lisa, Rapala, Alicja, Reynolds, Catherine J, Richards, Amy, Robathan, Matthew, Rosenheim, Joshua, Sambile, Genine, Schmidt, Nathalie M, Semper, Amanda, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel, Thomas, Stephen, Thornton, George D, Treibel, Thomas A, Tucker, Art, Veerapen, Jessry, Vijayakumar, Mohit, Welch, Sophie, Wodehouse, Theresa, Wynne, Lucinda, Zahedi, Dan, Gupta, Rishi K, Bell, Lucy C, Guerra-Assuncao, Jose A, Pollara, Gabriele, Whelan, Matthew, McKnight, Aine, and Chain, Benjamin M

Published
2021
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10. Evolution of long-term vaccine-induced and hybrid immunity in healthcare workers after different COVID-19 vaccine regimens

Author

Moore, Shona C., primary, Kronsteiner, Barbara, additional, Longet, Stephanie, additional, Adele, Sandra, additional, Deeks, Alexandra S., additional, Liu, Chang, additional, Dejnirattisai, Wanwisa, additional, Reyes, Laura Silva, additional, Meardon, Naomi, additional, Faustini, Sian, additional, Al-Taei, Saly, additional, Tipton, Tom, additional, Hering, Luisa M., additional, Angyal, Adrienn, additional, Brown, Rebecca, additional, Nicols, Alexander R., additional, Dobson, Susan L., additional, Supasa, Piyada, additional, Tuekprakhon, Aekkachai, additional, Cross, Andrew, additional, Tyerman, Jessica K., additional, Hornsby, Hailey, additional, Grouneva, Irina, additional, Plowright, Megan, additional, Zhang, Peijun, additional, Newman, Thomas A.H., additional, Nell, Jeremy M., additional, Abraham, Priyanka, additional, Ali, Mohammad, additional, Malone, Tom, additional, Neale, Isabel, additional, Phillips, Eloise, additional, Wilson, Joseph D., additional, Murray, Sam M., additional, Zewdie, Martha, additional, Shields, Adrian, additional, Horner, Emily C., additional, Booth, Lucy H., additional, Stafford, Lizzie, additional, Bibi, Sagida, additional, Wootton, Daniel G., additional, Mentzer, Alexander J., additional, Conlon, Christopher P., additional, Jeffery, Katie, additional, Matthews, Philippa C., additional, Pollard, Andrew J., additional, Brown, Anthony, additional, Rowland-Jones, Sarah L., additional, Mongkolsapaya, Juthathip, additional, Payne, Rebecca P., additional, Dold, Christina, additional, Lambe, Teresa, additional, Thaventhiran, James E.D., additional, Screaton, Gavin, additional, Barnes, Eleanor, additional, Hopkins, Susan, additional, Hall, Victoria, additional, Duncan, Christopher J.A., additional, Richter, Alex, additional, Carroll, Miles, additional, de Silva, Thushan I., additional, Klenerman, Paul, additional, Dunachie, Susanna, additional, and Turtle, Lance, additional

Published
2023
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11. Evolution of long-term vaccine-induced and hybrid immunity in healthcare workers after different COVID-19 vaccine regimens

Author

Moore, Shona C, Kronsteiner, Barbara, Longet, Stephanie, Adele, Sandra, Deeks, Alexandra S, Liu, Chang, Dejnirattisai, Wanwisa, Reyes, Laura Silva, Meardon, Naomi, Faustini, Sian, Al-Taei, Saly, Tipton, Tom, Hering, Luisa M, Angyal, Adrienn, Brown, Rebecca, Nicols, Alexander R, Dobson, Susan L, Supasa, Piyada, Tuekprakhon, Aekkachai, Cross, Andrew, Tyerman, Jessica K, Hornsby, Hailey, Grouneva, Irina, Plowright, Megan, Zhang, Peijun, Newman, Thomas AH, Nell, Jeremy M, Abraham, Priyanka, Ali, Mohammad, Malone, Tom, Neale, Isabel, Phillips, Eloise, Wilson, Joseph D, Murray, Sam M, Zewdie, Martha, Shields, Adrian, Horner, Emily C, Booth, Lucy H, Stafford, Lizzie, Bibi, Sagida, Wootton, Daniel G, Mentzer, Alexander J, Conlon, Christopher P, Jeffery, Katie, Matthews, Philippa C, Pollard, Andrew J, Brown, Anthony, Rowland-Jones, Sarah L, Mongkolsapaya, Juthathip, Payne, Rebecca P, Dold, Christina, Lambe, Teresa, Thaventhiran, James ED, Screaton, Gavin, Barnes, Eleanor, Hopkins, Susan, Hall, Victoria, Duncan, Christopher JA, Richter, Alex, Carroll, Miles, De Silva, Thushan I, Klenerman, Paul, Dunachie, Susanna, Turtle, Lance, PITCH Consortium, Nicols, Alexander R [0000-0002-1813-3819], Matthews, Philippa C [0000-0002-4036-4269], Barnes, Eleanor [0000-0002-0860-0831], Dunachie, Susanna [0000-0001-5665-6293], and Apollo - University of Cambridge Repository

Subjects
Vaccines, COVID-19 Vaccines, SARS-CoV-2, Translation to population health, Health Personnel, T cells, COVID-19, COVID vaccine, immunity, Antibodies, Neutralizing, Immunity, Humoral, antibody, ChAdOx1 nCoV-19, Humans, Prospective Studies, BNT162 Vaccine
Abstract

BACKGROUND: Both infection and vaccination, alone or in combination, generate antibody and T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the maintenance of such responses-and hence protection from disease-requires careful characterization. In a large prospective study of UK healthcare workers (HCWs) (Protective Immunity from T Cells in Healthcare Workers [PITCH], within the larger SARS-CoV-2 Immunity and Reinfection Evaluation [SIREN] study), we previously observed that prior infection strongly affected subsequent cellular and humoral immunity induced after long and short dosing intervals of BNT162b2 (Pfizer/BioNTech) vaccination. METHODS: Here, we report longer follow-up of 684 HCWs in this cohort over 6-9 months following two doses of BNT162b2 or AZD1222 (Oxford/AstraZeneca) vaccination and up to 6 months following a subsequent mRNA booster vaccination. FINDINGS: We make three observations: first, the dynamics of humoral and cellular responses differ; binding and neutralizing antibodies declined, whereas T and memory B cell responses were maintained after the second vaccine dose. Second, vaccine boosting restored immunoglobulin (Ig) G levels; broadened neutralizing activity against variants of concern, including Omicron BA.1, BA.2, and BA.5; and boosted T cell responses above the 6-month level after dose 2. Third, prior infection maintained its impact driving larger and broader T cell responses compared with never-infected people, a feature maintained until 6 months after the third dose. CONCLUSIONS: Broadly cross-reactive T cell responses are well maintained over time-especially in those with combined vaccine and infection-induced immunity ("hybrid" immunity)-and may contribute to continued protection against severe disease. FUNDING: Department for Health and Social Care, Medical Research Council.

Published
2023

12. Immunogenicity of SARSCoV2 Third Dose Vaccine Strategies in Immunocompromised Patients with Suboptimal Immunity Following Two Doses (OCTAVE-DUO): An Open-Label, Multi-Centre, Randomised, Controlled Phase III Trial

Author

Goodyear, Carl S., primary, Patel, Amit, additional, Barnes, Eleanor, additional, willicombe, michelle, additional, Siebert, Stefan, additional, de Silva, Thushan I., additional, Snowden, John A., additional, Lim, Sean, additional, Bowden, Sarah, additional, Billingham, Lucinda J., additional, Richter, Alex G., additional, Carroll, Miles W., additional, Carr, Edward J., additional, Beale, Rupert, additional, Rea, Daniel, additional, Parry, Helen, additional, Pirrie, Sarah, additional, Lim, Zixiang, additional, Satsangi, Jack, additional, Dunachie, Susanna, additional, Cook, Gordon, additional, Miller, Paul, additional, Basu, Neil, additional, Gilmour, Ashley, additional, Hodgkins, Anne-Marie, additional, Evans, Lili, additional, Hughes, Ana, additional, Longet, Stephanie, additional, Meacham, Georgina, additional, Yong, Kwee, additional, Ahearne, Matthew, additional, Koh, Mickey B. C., additional, Burns, Siobhan O., additional, Orchard, Kim, additional, Paterson, Caron, additional, McIlroy, Graham, additional, Murray, Sam M., additional, Thomson, Tina, additional, Dimitriadis, Stavros, additional, Goulston, Lyndsey, additional, Miller, Samantha, additional, Keillor, Victoria, additional, Prendecki, Maria, additional, Thomas, David, additional, Kirkham, Amanda, additional, McInnes, Iain, additional, and Kearns, Pamela, additional

Published
2023
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14. Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure

Author

Reynolds, Catherine J., Pade, Corinna, Gibbons, Joseph M., Otter, Ashley D., Lin, Kai-Min, Muñoz Sandoval, Diana, Pieper, Franziska P., Butler, David K., Liu, Siyi, Joy, George, Forooghi, Nasim, Treibel, Thomas A., Manisty, Charlotte, Moon, James C., Semper, Amanda, Brooks, Tim, McKnight, Áine, Altmann, Daniel M., Boyton, Rosemary J., Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Amin, Oliver E., Andiapen, Mervyn, Artico, Jessica, Augusto, João B., Baca, Georgina L., Bailey, Sasha N. L., Bhuva, Anish N., Boulter, Alex, Bowles, Ruth, Bracken, Olivia V., O’Brien, Ben, Bullock, Natalie, Captur, Gabriella, Carr, Olivia, Champion, Nicola, Chan, Carmen, Chandran, Aneesh, Coleman, Tom, Couto de Sousa, Jorge, Couto-Parada, Xose, Cross, Eleanor, Cutino-Moguel, Teresa, D’Arcangelo, Silvia, Davies, Rhodri H., Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O., Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Fontana, Marianna, Francis, Sasha, Gillespie, David, Gilroy, Derek, Hamblin, Matt, Harker, Gabrielle, Hemingway, Georgia, Hewson, Jacqueline, Heywood, Wendy, Hickling, Lauren M., Hicks, Bethany, Hingorani, Aroon D., Howes, Lee, Itua, Ivie, Jardim, Victor, Lee, Wing-Yiu Jason, Jensen, Melaniepetra, Jones, Jessica, Jones, Meleri, Kapil, Vikas, Kelly, Caoimhe, Kurdi, Hibba, Lambourne, Jonathan, Lloyd, Aaron, Louth, Sarah, Maini, Mala K., Mandadapu, Vineela, Menacho, Katia, Mfuko, Celina, Mills, Kevin, Millward, Sebastian, Mitchelmore, Oliver, Moon, Christopher, Moon, James, Murray, Sam M., Noursadeghi, Mahdad, Otter, Ashley, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Mihaela, Petersen, Steffen E., Piniera, Brian, Rannigan, Lisa, Rapala, Alicja, Richards, Amy, Robathan, Matthew, Rosenheim, Joshua, Rowe, Cathy, Royds, Matthew, Sackville West, Jane, Sambile, Genine, Schmidt, Nathalie M., Selman, Hannah, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel, Thomas, Stephen, Thornton, George D., Tucker, Art, Varghese, Ann, Veerapen, Jessry, Vijayakumar, Mohit, Warner, Tim, Welch, Sophie, White, Hannah, Wodehouse, Theresa, Wynne, Lucinda, Zahedi, Dan, Chain, Benjamin, and Medical Research Council (MRC)

Subjects
QR355, B-Lymphocytes, Science & Technology, Multidisciplinary, SARS-CoV-2, General Science & Technology, T-Lymphocytes, Immunization, Secondary, COVID-19, Cross Reactions, Antibodies, Viral, T-CELL IMMUNITY, Antibodies, Neutralizing, Multidisciplinary Sciences, Mice, INFECTION, Spike Glycoprotein, Coronavirus, Science & Technology - Other Topics, Animals, Humans, COVIDsortium Investigators§, COVIDsortium Immune Correlates Network§, BNT162 Vaccine
Abstract

INTRODUCTION B.1.1.529 (Omicron) and its subvariants pose new challenges for control of the COVID-19 pandemic. Although vaccinated populations are relatively protected from severe disease and death, countries with high vaccine uptake are experiencing substantial caseloads with breakthrough infection and frequent reinfection. RATIONALE We analyzed cross-protective immunity against B.1.1.529 (Omicron) in triple-vaccinated health care workers (HCWs) with different immune-imprinted histories of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the ancestral Wuhan Hu-1, B.1.1.7 (Alpha), and B.1.617.2 (Delta) waves and after infection during the B.1.1.529 (Omicron) wave in previously infection-naïve individuals and those with hybrid immunity, to investigate whether B.1.1.529 (Omicron) infection could further boost adaptive immunity. Spike subunit 1 (S1) receptor binding domain (RBD) and whole spike binding, live virus neutralizing antibody (nAb) potency, memory B cell (MBC) frequency, and T cell responses against peptide pools and naturally processed antigen were assessed. RESULTS B and T cell recognition and nAb potency were boosted against previous variants of concern (VOCs) in triple-vaccinated HCWs, but this enhanced immunity was attenuated against B.1.1.529 (Omicron) itself. Furthermore, immune imprinting after B.1.1.7 (Alpha) infection resulted in reduced durability of antibody binding against B.1.1.529 (Omicron), and S1 RBD and whole spike VOC binding correlated poorly with live virus nAb potency. Half of triple-vaccinated HCWs showed no T cell response to B.1.1.529 (Omicron) S1 processed antigen, and all showed reduced responses to the B.1.1.529 (Omicron) peptide pool, irrespective of SARS-CoV-2 infection history. Mapping T cell immunity in class II human leukocyte antigen transgenics showed that individual spike mutations could result in loss or gain of T cell epitope recognition, with changes to T cell effector and regulatory programs. Triple-vaccinated, previously infection-naïve individuals infected during the B.1.1.529 (Omicron) wave showed boosted cross-reactive S1 RBD and whole spike binding, live virus nAb potency, and T cell immunity against previous VOCs but less so against B.1.1.529 (Omicron) itself. Immune imprinting from prior Wuhan Hu-1 infection abrogated any enhanced cross-reactive antibody binding, T cell recognition, MBC frequency, or nAb potency after B.1.1.529 (Omicron) infection. CONCLUSION Vaccine boosting results in distinct, imprinted patterns of hybrid immunity with different combinations of SARS-CoV-2 infection and vaccination. Immune protection is boosted by B.1.1.529 (Omicron) infection in the triple-vaccinated, previously infection-naïve individuals, but this boosting is lost with prior Wuhan Hu-1 imprinting. This “hybrid immune damping” indicates substantial subversion of immune recognition and differential modulation through immune imprinting and may be the reason why the B.1.1.529 (Omicron) wave has been characterized by breakthrough infection and frequent reinfection with relatively preserved protection against severe disease in triple-vaccinated individuals.

Published
2022

15. Impaired humoral and cellular response to primary COVID ‐19 vaccination in patients less than 2 years after allogeneic bone marrow transplant

Author

Murray, Sam M., primary, Barbanti, Maria, additional, Campbell, Cori, additional, Brown, Anthony, additional, Chen, Lucia, additional, Dhanapal, Jay, additional, Tseu, Bing, additional, Pervaiz, Omer, additional, Peters, Louis, additional, Springett, Sally, additional, Danby, Robert, additional, Adele, Sandra, additional, Phillips, Eloise, additional, Malone, Tom, additional, Amini, Ali, additional, Stafford, Lizzie, additional, Deeks, Alexandra S., additional, Dunachie, Susanna, additional, Klenerman, Paul, additional, Peniket, Andrew, additional, Barnes, Eleanor, additional, and Kesavan, Murali, additional

Published
2022
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16. Evolution of long-term vaccine induced and hybrid immunity in healthcare workers after different COVID-19 vaccination regimens: a longitudinal observational cohort study

Author

Moore, Shona C., primary, Kronsteiner, Barbara, additional, Longet, Stephanie, additional, Adele, Sandra, additional, Deeks, Alexandra S., additional, Liu, Chang, additional, Dejnirattisai, Wanwisa, additional, Reyes, Laura Silva, additional, Meardon, Naomi, additional, Faustini, Sian, additional, Al-Taei, Saly, additional, Tipton, Tom, additional, Hering, Luisa M, additional, Angyal, Adrienn, additional, Brown, Rebecca, additional, Nicols, Alexander R, additional, Dobson, Susan L, additional, Supasa, Piyada, additional, Tuekprakhon, Aekkachai, additional, Cross, Andrew, additional, Tyerman, Jessica K, additional, Hornsby, Hailey, additional, Grouneva, Irina, additional, Plowright, Megan, additional, Zhang, Peijun, additional, Newman, Thomas A.H., additional, Nell, Jeremy M., additional, Abraham, Priyanka, additional, Ali, Mohammad, additional, Malone, Tom, additional, Neale, Isabel, additional, Phillips, Eloise, additional, Wilson, Joseph D., additional, Murray, Sam M., additional, Zewdie, Martha, additional, Shields, Adrian, additional, Horner, Emily C., additional, Booth, Lucy H., additional, Stafford, Lizzie, additional, Bibi, Sagida, additional, Wootton, Daniel G., additional, Mentzer, Alexander J., additional, Conlon, Christopher P., additional, Jeffery, Katie, additional, Matthews, Philippa C., additional, Pollard, Andrew J., additional, Brown, Anthony, additional, Rowland-Jones, Sarah L., additional, Mongkolsapaya, Juthathip, additional, Payne, Rebecca P., additional, Dold, Christina, additional, Lambe, Teresa, additional, Thaventhiran, James E.D., additional, Screaton, Gavin, additional, Barnes, Eleanor, additional, Hopkins, Susan, additional, Hall, Victoria, additional, Duncan, Christopher JA, additional, Richter, Alex, additional, Carroll, Miles, additional, de Silva, Thushan I., additional, Klenerman, Paul, additional, Dunachie, Susanna, additional, and Turtle, Lance, additional

Published
2022
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17. Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response

Author

Doykov, Ivan, Baldwin, Tomas, Spiewak, Justyna, Gilmour, Kimberly C., Gibbons, Joseph M., Pade, Corinna, Reynolds, Catherine J., McKnight, Áine, Noursadeghi, Mahdad, Maini, Mala K., Manisty, Charlotte, Treibel, Thomas, Captur, Gabriella, Fontana, Marianna, Boyton, Rosemary J., Altmann, Daniel M., Brooks, Tim, Semper, Amanda, Moon, James C., Mills, Kevin, Heywood, Wendy E., Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Amin, Oliver E., Andiapen, Mervyn, Artico, Jessica, Augusto, João B., Baca, Georgina L., Bailey, Sasha N.L., Bhuva, Anish N., Boulter, Alex, Bowles, Ruth, Bracken, Olivia V., O’Brien, Ben, Bullock, Natalie, Butler, David K., Carr, Olivia, Champion, Nicola, Chan, Carmen, Chandran, Aneesh, Coleman, Tom, Couto de Sousa, Jorge, Couto-Parada, Xose, Cross, Eleanor, Cutino-Moguel, Teresa, D’Arcangelo, Silvia, Davies, Rhodri H., Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O., Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Forooghi, Nasim, Francis, Sasha, Gillespie, David, Gilroy, Derek, Hamblin, Matt, Harker, Gabrielle, Hemingway, Georgia, Hewson, Jacqueline, Heywood, Wendy, Hickling, Lauren M., Hicks, Bethany, Hingorani, Aroon D., Howes, Lee, Itua, Ivie, Jardim, Victor, Lee, Wing-Yiu Jason, Jensen, Melaniepetra, Jones, Jessica, Jones, Meleri, Joy, George, Kapil, Vikas, Kelly, Caoimhe, Kurdi, Hibba, Lambourne, Jonathan, Lin, Kai-Min, Liu, Siyi, Lloyd, Aaron, Louth, Sarah, Mandadapu, Vineela, Menacho, Katia, Mfuko, Celina, Millward, Sebastian, Mitchelmore, Oliver, Moon, Christopher, Moon, James, Sandoval, Diana Muñoz, Murray, Sam M., Otter, Ashley, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Mihaela, Petersen, Steffen E., Piniera, Brian, Pieper, Franziska P., Rannigan, Lisa, Rapala, Alicja, Richards, Amy, Robathan, Matthew, Rosenheim, Joshua, Rowe, Cathy, Royds, Matthew, West, Jane Sackville, Sambile, Genine, Schmidt, Nathalie M., Selman, Hannah, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel J., Thomas, Stephen, Thornton, George D., Treibel, Thomas A., Tucker, Art, Varghese, Ann, Veerapen, Jessry, Vijayakumar, Mohit, Warner, Tim, Welch, Sophie, White, Hannah, Wodehouse, Theresa, Wynne, Lucinda, Zahedi, Dan, Doykov, Ivan, Baldwin, Tomas, Spiewak, Justyna, Gilmour, Kimberly C., Gibbons, Joseph M., Pade, Corinna, Reynolds, Catherine J., McKnight, Áine, Noursadeghi, Mahdad, Maini, Mala K., Manisty, Charlotte, Treibel, Thomas, Captur, Gabriella, Fontana, Marianna, Boyton, Rosemary J., Altmann, Daniel M., Brooks, Tim, Semper, Amanda, Moon, James C., Mills, Kevin, Heywood, Wendy E., Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Amin, Oliver E., Andiapen, Mervyn, Artico, Jessica, Augusto, João B., Baca, Georgina L., Bailey, Sasha N.L., Bhuva, Anish N., Boulter, Alex, Bowles, Ruth, Bracken, Olivia V., O’Brien, Ben, Bullock, Natalie, Butler, David K., Carr, Olivia, Champion, Nicola, Chan, Carmen, Chandran, Aneesh, Coleman, Tom, Couto de Sousa, Jorge, Couto-Parada, Xose, Cross, Eleanor, Cutino-Moguel, Teresa, D’Arcangelo, Silvia, Davies, Rhodri H., Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O., Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Forooghi, Nasim, Francis, Sasha, Gillespie, David, Gilroy, Derek, Hamblin, Matt, Harker, Gabrielle, Hemingway, Georgia, Hewson, Jacqueline, Heywood, Wendy, Hickling, Lauren M., Hicks, Bethany, Hingorani, Aroon D., Howes, Lee, Itua, Ivie, Jardim, Victor, Lee, Wing-Yiu Jason, Jensen, Melaniepetra, Jones, Jessica, Jones, Meleri, Joy, George, Kapil, Vikas, Kelly, Caoimhe, Kurdi, Hibba, Lambourne, Jonathan, Lin, Kai-Min, Liu, Siyi, Lloyd, Aaron, Louth, Sarah, Mandadapu, Vineela, Menacho, Katia, Mfuko, Celina, Millward, Sebastian, Mitchelmore, Oliver, Moon, Christopher, Moon, James, Sandoval, Diana Muñoz, Murray, Sam M., Otter, Ashley, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Mihaela, Petersen, Steffen E., Piniera, Brian, Pieper, Franziska P., Rannigan, Lisa, Rapala, Alicja, Richards, Amy, Robathan, Matthew, Rosenheim, Joshua, Rowe, Cathy, Royds, Matthew, West, Jane Sackville, Sambile, Genine, Schmidt, Nathalie M., Selman, Hannah, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel J., Thomas, Stephen, Thornton, George D., Treibel, Thomas A., Tucker, Art, Varghese, Ann, Veerapen, Jessry, Vijayakumar, Mohit, Warner, Tim, Welch, Sophie, White, Hannah, Wodehouse, Theresa, Wynne, Lucinda, and Zahedi, Dan

Abstract

Determining the protection an individual has to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VoCs) is crucial for future immune surveillance, vaccine development, and understanding of the changing immune response. We devised an informative assay to current ELISA-based serology using multiplexed, baited, targeted proteomics for direct detection of multiple proteins in the SARS-CoV-2 anti-spike antibody immunocomplex. Serum from individuals collected after infection or first- and second-dose vaccination demonstrates this approach and shows concordance with existing serology and neutralization. Our assays show altered responses of both immunoglobulins and complement to the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.1) VoCs and a reduced response to Omicron (B1.1.1529). We were able to identify individuals who had prior infection, and observed that C1q is closely associated with IgG1 (r > 0.82) and may better reflect neutralization to VoCs. Analyzing additional immunoproteins beyond immunoglobulin (Ig) G, provides important information about our understanding of the response to infection and vaccination.

Published
2022

18. Evolution of Long-Term Hybrid Immunity in Healthcare Workers after Different Covid-19 Vaccination Regimens: A Longitudinal Observational Cohort Study

Author

Moore, Shona, primary, Kronsteiner, Barbara, additional, Longet, Stephanie, additional, Adele, Sandra, additional, Deeks, Alexandra, additional, Liu, Chang, additional, Dejnirattisai, Wanwisa, additional, Silva Reyes, Laura, additional, Meardon, Naomi, additional, Faustini, Sian, additional, Al-Taei, Saly, additional, Tipton, Tom, additional, Hering, Luisa M., additional, Angyal, Adrienn, additional, Brown, Rebecca, additional, Nicols, Alexander R., additional, Dobson, Sue L., additional, Supasa, Piyada, additional, Tuekprakhon, Aekkachai, additional, Cross, Andrew, additional, Tyerman, Jessica K., additional, Hornsby, Hailey, additional, Grouneva, Irina, additional, Plowright, Megan, additional, Zhang, Peijun, additional, Newman, Thomas, additional, Nell, Jeremy M., additional, Abraham, Priyanka, additional, Ali, Mohammad, additional, Malone, Tom, additional, Neale, Isabel, additional, Phillips, Eloise, additional, Wilson, Joseph D., additional, Murray, Sam M., additional, Shields, Adrian, additional, Horner, Emily C., additional, Booth, Lucy H., additional, Stafford, Lizzie, additional, Bibi, Sagida, additional, Wootton, Dan G., additional, Mentzer, Alexander J., additional, Conlon, Christopher P., additional, Jeffery, Katie, additional, Matthews, Philippa C., additional, Pollard, Andrew J., additional, Brown, Anthony, additional, Rowland-Jones, Sarah L., additional, Mongkolspaya, Juthathip, additional, Payne, Rebecca P., additional, Dold, Christina, additional, Lambe, Teresa, additional, Thaventhiran, James, additional, Screaton, Gavin R., additional, Barnes, Eleanor, additional, Hopkins, Susan, additional, Hall, Victoria Jane, additional, Duncan, Christopher JA, additional, Richter, Alex G., additional, Carroll, Miles W., additional, de Silva, Thushan I., additional, Klenerman, Paul, additional, Dunachie, Susanna, additional, Turtle, Lance, additional, and Consortium, PITCH, additional

Published
2022
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19. Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2

Author

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

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

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

Published
2021

20. Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection: a nested, case-control diagnostic accuracy study

Author

Gupta, Rishi K, primary, Rosenheim, Joshua, additional, Bell, Lucy C, additional, Chandran, Aneesh, additional, Guerra-Assuncao, Jose A, additional, Pollara, Gabriele, additional, Whelan, Matthew, additional, Artico, Jessica, additional, Joy, George, additional, Kurdi, Hibba, additional, Altmann, Daniel M, additional, Boyton, Rosemary J, additional, Maini, Mala K, additional, McKnight, Aine, additional, Lambourne, Jonathan, additional, Cutino-Moguel, Teresa, additional, Manisty, Charlotte, additional, Treibel, Thomas A, additional, Moon, James C, additional, Chain, Benjamin M, additional, Noursadeghi, Mahdad, additional, Abbass, Hakam, additional, Abiodun, Aderonke, additional, Alfarih, Mashael, additional, Alldis, Zoe, additional, Amin, Oliver E, additional, Andiapen, Mervyn, additional, Augusto, João B, additional, Baca, Georgiana L, additional, Bailey, Sasha NL, additional, Bhuva, Anish N, additional, Boulter, Alex, additional, Bowles, Ruth, additional, Bracken, Olivia V, additional, O'Brien, Ben, additional, Brooks, Tim, additional, Bullock, Natalie, additional, Butler, David K, additional, Captur, Gabriella, additional, Champion, Nicola, additional, Chan, Carmen, additional, Collier, David, additional, Couto de Sousa, Jorge, additional, Couto-Parada, Xose, additional, Davies, Rhodri H, additional, Douglas, Brooke, additional, Di Genova, Cecilia, additional, Dieobi-Anene, Keenan, additional, Diniz, Mariana O, additional, Ellis, Anaya, additional, Feehan, Karen, additional, Finlay, Malcolm, additional, Fontana, Marianna, additional, Forooghi, Nasim, additional, Gaier, Celia, additional, Gibbons, Joseph M, additional, Gilroy, Derek, additional, Hamblin, Matt, additional, Harker, Gabrielle, additional, Hewson, Jacqueline, additional, Hickling, Lauren M, additional, Hingorani, Aroon D, additional, Howes, Lee, additional, Hughes, Alun, additional, Hughes, Gemma, additional, Hughes, Rebecca, additional, Itua, Ivie, additional, Jardim, Victor, additional, Lee, Wing-Yiu Jason, additional, Jensen, Melaniepetra, additional, Jones, Jessica, additional, Jones, Meleri, additional, Kapil, Vikas, additional, Lin, Kai-Min, additional, Louth, Sarah, additional, Mandadapu, Vineela, additional, Manisty,, Charlotte, additional, McKnight, Áine, additional, Menacho, Katia, additional, Mfuko, Celina, additional, Mitchelmore, Oliver, additional, Moon, Christopher, additional, Moon,, James C, additional, Munoz Sandoval, Diana, additional, Murray, Sam M, additional, Otter, Ashley, additional, Pade, Corinna, additional, Palma, Susana, additional, Parker, Ruth, additional, Patel, Kush, additional, Pawarova, Babita, additional, Petersen, Steffen E, additional, Piniera, Brian, additional, Pieper, Franziska P, additional, Pope, Daniel, additional, Prossora, Maria, additional, Rannigan, Lisa, additional, Rapala, Alicja, additional, Reynolds, Catherine J, additional, Richards, Amy, additional, Robathan, Matthew, additional, Sambile, Genine, additional, Schmidt, Nathalie M, additional, Semper, Amanda, additional, Seraphim, Andreas, additional, Simion, Mihaela, additional, Smit, Angelique, additional, Sugimoto, Michelle, additional, Swadling, Leo, additional, Taylor, Stephen, additional, Temperton, Nigel, additional, Thomas, Stephen, additional, Thornton, George D, additional, Tucker, Art, additional, Veerapen, Jessry, additional, Vijayakumar, Mohit, additional, Welch, Sophie, additional, Wodehouse, Theresa, additional, Wynne, Lucinda, additional, and Zahedi, Dan, additional

Published
2021
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21. Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy.

Author

Pinato, David J., primary, Murray, Sam M, additional, Forner, Alejandro, additional, Kaneko, Takahiro, additional, Fessas, Petros, additional, Toniutto, Pierluigi, additional, Mínguez, Beatriz, additional, Cacciato, Valentina, additional, Avellini, Claudio, additional, Diaz, Alba, additional, Boyton, Rosemary J., additional, Altmann, Daniel M., additional, Goldin, Robert D, additional, Akarca, Ayse U, additional, Marafioti, Teresa, additional, Mauri, Francesco A, additional, Casagrande, Edoardo, additional, Grillo, Federica, additional, Giannini, Edoardo, additional, Bhoori, Sherrie, additional, and Mazzaferro, Vincenzo, additional

Published
2021
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22. Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection: a nested, case-control diagnostic accuracy study

Author

Gupta, Rishi K, Rosenheim, Joshua, Bell, Lucy C, Chandran, Aneesh, Guerra-Assuncao, Jose A, Pollara, Gabriele, Whelan, Matthew, Artico, Jessica, Joy, George, Kurdi, Hibba, Altmann, Daniel M, Boyton, Rosemary J, Maini, Mala K, McKnight, Aine, Lambourne, Jonathan, Cutino-Moguel, Teresa, Manisty, Charlotte, Treibel, Thomas A, Moon, James C, Chain, Benjamin M, Noursadeghi, Mahdad, Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Amin, Oliver E, Andiapen, Mervyn, Augusto, João B, Baca, Georgiana L, Bailey, Sasha NL, Bhuva, Anish N, Boulter, Alex, Bowles, Ruth, Bracken, Olivia V, O'Brien, Ben, Brooks, Tim, Bullock, Natalie, Butler, David K, Captur, Gabriella, Champion, Nicola, Chan, Carmen, Collier, David, Couto de Sousa, Jorge, Couto-Parada, Xose, Davies, Rhodri H, Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O, Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Fontana, Marianna, Forooghi, Nasim, Gaier, Celia, Gibbons, Joseph M, Gilroy, Derek, Hamblin, Matt, Harker, Gabrielle, Hewson, Jacqueline, Hickling, Lauren M, Hingorani, Aroon D, Howes, Lee, Hughes, Alun, Hughes, Gemma, Hughes, Rebecca, Itua, Ivie, Jardim, Victor, Lee, Wing-Yiu Jason, Jensen, Melaniepetra, Jones, Jessica, Jones, Meleri, Kapil, Vikas, Lin, Kai-Min, Louth, Sarah, Mandadapu, Vineela, Manisty,, Charlotte, McKnight, Áine, Menacho, Katia, Mfuko, Celina, Mitchelmore, Oliver, Moon, Christopher, Moon,, James C, Munoz Sandoval, Diana, Murray, Sam M, Otter, Ashley, Pade, Corinna, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Babita, Petersen, Steffen E, Piniera, Brian, Pieper, Franziska P, Pope, Daniel, Prossora, Maria, Rannigan, Lisa, Rapala, Alicja, Reynolds, Catherine J, Richards, Amy, Robathan, Matthew, Sambile, Genine, Schmidt, Nathalie M, Semper, Amanda, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel J., Thomas, Stephen, Thornton, George D, Tucker, Art, Veerapen, Jessry, Vijayakumar, Mohit, Welch, Sophie, Wodehouse, Theresa, Wynne, Lucinda, Zahedi, Dan, Gupta, Rishi K, Rosenheim, Joshua, Bell, Lucy C, Chandran, Aneesh, Guerra-Assuncao, Jose A, Pollara, Gabriele, Whelan, Matthew, Artico, Jessica, Joy, George, Kurdi, Hibba, Altmann, Daniel M, Boyton, Rosemary J, Maini, Mala K, McKnight, Aine, Lambourne, Jonathan, Cutino-Moguel, Teresa, Manisty, Charlotte, Treibel, Thomas A, Moon, James C, Chain, Benjamin M, Noursadeghi, Mahdad, Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Amin, Oliver E, Andiapen, Mervyn, Augusto, João B, Baca, Georgiana L, Bailey, Sasha NL, Bhuva, Anish N, Boulter, Alex, Bowles, Ruth, Bracken, Olivia V, O'Brien, Ben, Brooks, Tim, Bullock, Natalie, Butler, David K, Captur, Gabriella, Champion, Nicola, Chan, Carmen, Collier, David, Couto de Sousa, Jorge, Couto-Parada, Xose, Davies, Rhodri H, Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O, Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Fontana, Marianna, Forooghi, Nasim, Gaier, Celia, Gibbons, Joseph M, Gilroy, Derek, Hamblin, Matt, Harker, Gabrielle, Hewson, Jacqueline, Hickling, Lauren M, Hingorani, Aroon D, Howes, Lee, Hughes, Alun, Hughes, Gemma, Hughes, Rebecca, Itua, Ivie, Jardim, Victor, Lee, Wing-Yiu Jason, Jensen, Melaniepetra, Jones, Jessica, Jones, Meleri, Kapil, Vikas, Lin, Kai-Min, Louth, Sarah, Mandadapu, Vineela, Manisty,, Charlotte, McKnight, Áine, Menacho, Katia, Mfuko, Celina, Mitchelmore, Oliver, Moon, Christopher, Moon,, James C, Munoz Sandoval, Diana, Murray, Sam M, Otter, Ashley, Pade, Corinna, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Babita, Petersen, Steffen E, Piniera, Brian, Pieper, Franziska P, Pope, Daniel, Prossora, Maria, Rannigan, Lisa, Rapala, Alicja, Reynolds, Catherine J, Richards, Amy, Robathan, Matthew, Sambile, Genine, Schmidt, Nathalie M, Semper, Amanda, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel J., Thomas, Stephen, Thornton, George D, Tucker, Art, Veerapen, Jessry, Vijayakumar, Mohit, Welch, Sophie, Wodehouse, Theresa, Wynne, Lucinda, and Zahedi, Dan

Abstract

Background We hypothesised that host-response biomarkers of viral infections might contribute to early identification of individuals infected with SARS-CoV-2, which is critical to breaking the chains of transmission. We aimed to evaluate the diagnostic accuracy of existing candidate whole-blood transcriptomic signatures for viral infection to predict positivity of nasopharyngeal SARS-CoV-2 PCR testing.Methods We did a nested case-control diagnostic accuracy study among a prospective cohort of health-care workers (aged ≥18 years) at St Bartholomew’s Hospital (London, UK) undergoing weekly blood and nasopharyngeal swab sampling for whole-blood RNA sequencing and SARS-CoV-2 PCR testing, when fit to attend work. We identified candidate blood transcriptomic signatures for viral infection through a systematic literature search. We searched MEDLINE for articles published between database inception and Oct 12, 2020, using comprehensive MeSH and keyword terms for “viral infection”, “transcriptome”, “biomarker”, and “blood”. We reconstructed signature scores in blood RNA sequencing data and evaluated their diagnostic accuracy for contemporaneous SARS-CoV-2 infection, compared with the gold standard of SARS-CoV-2 PCR testing, by quantifying the area under the receiver operating characteristic curve (AUROC), sensitivities, and specificities at a standardised Z score of at least 2 based on the distribution of signature scores in test-negative controls. We used pairwise DeLong tests compared with the most discriminating signature to identify the subset of best performing biomarkers. We evaluated associations between signature expression, viral load (using PCR cycle thresholds), and symptom status visually and using Spearman rank correlation. The primary outcome was the AUROC for discriminating between samples from participants who tested negative throughout the study (test-negative controls) and samples from participants with PCR-confirmed SARS-CoV-2 infection (test-positive part

Published
2021

24. Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection

Author

Reynolds, Catherine J., Swadling, Leo, Gibbons, Joseph M., Pade, Corinna, Jensen, Melanie P., Diniz, Mariana O., Schmidt, Nathalie M., Butler, David K., Amin, Oliver E., Bailey, Sasha N. L., Murray, Sam M., Pieper, Franziska P., Taylor, Stephen, Jones, Jessica, Jones, Meleri, Lee, Wing-Yiu Jason, Rosenheim, Joshua, Chandran, Aneesh, Joy, George, Di Genova, Cecilia, Temperton, Nigel, Lambourne, Jonathan, Cutino-Moguel, Teresa, Andiapen, Mervyn, Fontana, Marianna, Smit, Angelique, Semper, Amanda, O’Brien, Ben, Chain, Benjamin, Brooks, Tim, Manisty, Charlotte, Treibel, Thomas, Moon, James C., Noursadeghi, Mahdad, Altmann, Daniel M., Maini, Mala K., McKnight, Áine, Boyton, Rosemary J., Reynolds, Catherine J., Swadling, Leo, Gibbons, Joseph M., Pade, Corinna, Jensen, Melanie P., Diniz, Mariana O., Schmidt, Nathalie M., Butler, David K., Amin, Oliver E., Bailey, Sasha N. L., Murray, Sam M., Pieper, Franziska P., Taylor, Stephen, Jones, Jessica, Jones, Meleri, Lee, Wing-Yiu Jason, Rosenheim, Joshua, Chandran, Aneesh, Joy, George, Di Genova, Cecilia, Temperton, Nigel, Lambourne, Jonathan, Cutino-Moguel, Teresa, Andiapen, Mervyn, Fontana, Marianna, Smit, Angelique, Semper, Amanda, O’Brien, Ben, Chain, Benjamin, Brooks, Tim, Manisty, Charlotte, Treibel, Thomas, Moon, James C., Noursadeghi, Mahdad, Altmann, Daniel M., Maini, Mala K., McKnight, Áine, and Boyton, Rosemary J.

Abstract

Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection.

Published
2020

25. Examining the Immunological Effects of COVID-19 Vaccination in Patients with Conditions Potentially Leading to Diminished Immune Response Capacity – The OCTAVE Trial

Author

Kearns, Pamela, primary, Siebert, Stefan, additional, willicombe, michelle, additional, Gaskell, Charlotte, additional, Kirkham, Amanda, additional, Pirrie, Sarah, additional, Bowden, Sarah, additional, Magwaro, Sophia, additional, Hughes, Ana, additional, Lim, Zixiang, additional, Dimitriadis, Stavros, additional, Murray, Sam M., additional, Marjot, Thomas, additional, Win, Zay, additional, Irwin, Sophie L., additional, Meacham, Georgina, additional, Richter, Alex G., additional, Kelleher, Peter, additional, Satsangi, Jack, additional, Miller, Paul, additional, Rea, Daniel, additional, Cook, Gordon, additional, Turtle, Lance, additional, Klenerman, Paul, additional, Dunachie, Susanna, additional, Basu, Neil, additional, de Silva, Thushan I., additional, Thomas, David, additional, Barnes, Eleanor, additional, Goodyear, Carl S., additional, and McInnes, Iain, additional

Published
2021
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26. Tu1866 SALIVARY MICROBIOTA COMPOSITION IS ASSOCIATED WITH ANTIBODY RESPONSE FOLLOWING COVID-19 VACCINATION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE, CIRRHOSIS AND LIVER TRANSPLANTATION

Author

Mullish, Benjamin H., Danckert, Nathan P., Patel, Ria, Irwin, Sophie L., Dimitriadis, Stavros, Murray, Sam M., Forlano, Roberta, Roberts, Lauren, Blanco, Jesus Miguens, Faustini, Sian, Richter, Alex G., Powell, Nick, Thursz, Mark R., Manousou, Pinelopi, Barnes, Eleanor, Marchesi, Julian, Marjot, Thomas, and Alexander, James L.

Published
2023
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27. Evolution of long-term vaccine induced and hybrid immunity in healthcare workers after different COVID19 vaccine regimens: a longitudinal cohort study

Author

Moore, Shona C., Kronsteiner, Barbara, Longet, Stephanie, Adele, Sandra, Deeks, Alexandra S., Liu, Chang, Dejnirattisai, Wanwisa, Reyes, Laura Silva, Meardon, Naomi, Faustini, Sian, Al-Taei, Saly, Tipton, Tom, Hering, Luisa M., Angyal, Adrienn, Brown, Rebecca, Nicols, Alexander R., Dobson, Susan L., Supasa, Piyada, Tuekprakhon, Aekkachai, Cross, Andrew, Tyerman, Jessica K., Hornsby, Hailey, Grouneva, Irina, Plowright, Megan, Zhang, Peijun, Newman, Thomas A.H., Nell, Jeremy M., Abraham, Priyanka, Ali, Mohammad, Malone, Tom, Neale, Isabel, Phillips, Eloise, Wilson, Joseph D., Murray, Sam M., Zewdie, Martha, Shields, Adrian, Horner, Emily C., Booth, Lucy H., Stafford, Lizzie, Bibi, Sagida, Wootton, Daniel G., Mentzer, Alexander J., Conlon, Christopher P., Jeffery, Katie, Matthews, Philippa C., Pollard, Andrew J., Brown, Anthony, Rowland-Jones, Sarah L., Mongkolsapaya, Juthathip, Payne, Rebecca P., Dold, Christina, Lambe, Teresa, Thaventhiran, James E.D., Screaton, Gavin, Barnes, Eleanor, Hopkins, Susan, Hall, Victoria, Duncan, Christopher JA., Richter, Alex, Carroll, Miles, de Silva, Thushan I., Klenerman, Paul, Dunachie, Susanna, and Turtle, Lance

Abstract

Both infection and vaccination, alone or in combination, generate antibody and T cell responses against SARS-CoV-2. However, the maintenance of such responses – and hence protection from disease – requires careful characterisation. In a large prospective study of UK healthcare workers (Protective immunity from T cells in Healthcare workers (PITCH), within the larger SARS-CoV-2 immunity & reinfection evaluation (SIREN) study) we previously observed that prior infection impacted strongly on subsequent cellular and humoral immunity induced after long and short dosing intervals of BNT162b2 (Pfizer/BioNTech) vaccination.

Published
2023
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28. Immune boosting by B.1.1.529 ( Omicron) depends on previous SARS-CoV-2 exposure.

Author

Reynolds CJ, Pade C, Gibbons JM, Otter AD, Lin KM, Muñoz Sandoval D, Pieper FP, Butler DK, Liu S, Joy G, Forooghi N, Treibel TA, Manisty C, Moon JC, Semper A, Brooks T, McKnight Á, Altmann DM, Boyton RJ, Abbass H, Abiodun A, Alfarih M, Alldis Z, Altmann DM, Amin OE, Andiapen M, Artico J, Augusto JB, Baca GL, Bailey SNL, Bhuva AN, Boulter A, Bowles R, Boyton RJ, Bracken OV, O'Brien B, Brooks T, Bullock N, Butler DK, Captur G, Carr O, Champion N, Chan C, Chandran A, Coleman T, Couto de Sousa J, Couto-Parada X, Cross E, Cutino-Moguel T, D'Arcangelo S, Davies RH, Douglas B, Di Genova C, Dieobi-Anene K, Diniz MO, Ellis A, Feehan K, Finlay M, Fontana M, Forooghi N, Francis S, Gibbons JM, Gillespie D, Gilroy D, Hamblin M, Harker G, Hemingway G, Hewson J, Heywood W, Hickling LM, Hicks B, Hingorani AD, Howes L, Itua I, Jardim V, Lee WJ, Jensen M, Jones J, Jones M, Joy G, Kapil V, Kelly C, Kurdi H, Lambourne J, Lin KM, Liu S, Lloyd A, Louth S, Maini MK, Mandadapu V, Manisty C, McKnight Á, Menacho K, Mfuko C, Mills K, Millward S, Mitchelmore O, Moon C, Moon J, Muñoz Sandoval D, Murray SM, Noursadeghi M, Otter A, Pade C, Palma S, Parker R, Patel K, Pawarova M, Petersen SE, Piniera B, Pieper FP, Rannigan L, Rapala A, Reynolds CJ, Richards A, Robathan M, Rosenheim J, Rowe C, Royds M, Sackville West J, Sambile G, Schmidt NM, Selman H, Semper A, Seraphim A, Simion M, Smit A, Sugimoto M, Swadling L, Taylor S, Temperton N, Thomas S, Thornton GD, Treibel TA, Tucker A, Varghese A, Veerapen J, Vijayakumar M, Warner T, Welch S, White H, Wodehouse T, Wynne L, Zahedi D, Chain B, and Moon JC

Subjects
Animals, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, Cross Reactions, Humans, Mice, Spike Glycoprotein, Coronavirus genetics, Spike Glycoprotein, Coronavirus immunology, B-Lymphocytes immunology, BNT162 Vaccine immunology, BNT162 Vaccine therapeutic use, COVID-19 immunology, COVID-19 prevention & control, Immunization, Secondary, SARS-CoV-2 genetics, SARS-CoV-2 immunology, T-Lymphocytes immunology
Abstract

The Omicron, or Pango lineage B.1.1.529, variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection against severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple BioNTech BNT162b2 messenger RNA-vaccinated health care workers (HCWs) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple-vaccinated individuals, but the magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCWs who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529.

Published
2022
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29. Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection.

Author

Reynolds CJ, Swadling L, Gibbons JM, Pade C, Jensen MP, Diniz MO, Schmidt NM, Butler DK, Amin OE, Bailey SNL, Murray SM, Pieper FP, Taylor S, Jones J, Jones M, Lee WJ, Rosenheim J, Chandran A, Joy G, Di Genova C, Temperton N, Lambourne J, Cutino-Moguel T, Andiapen M, Fontana M, Smit A, Semper A, O'Brien B, Chain B, Brooks T, Manisty C, Treibel T, Moon JC, Noursadeghi M, Altmann DM, Maini MK, McKnight Á, and Boyton RJ

Subjects
Antibodies, Neutralizing blood, Antibodies, Viral blood, Antibodies, Viral immunology, Case-Control Studies, Cross-Sectional Studies, Humans, SARS-CoV-2 immunology, Antibodies, Neutralizing immunology, Asymptomatic Infections, COVID-19 immunology, T-Lymphocytes immunology
Abstract

Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection., (Copyright © 2020, American Association for the Advancement of Science.)

Published
2020
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