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1. 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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2. 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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4. 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

5. The Alpha variant was not associated with excess nosocomial SARS-CoV-2 infection in a multi-centre UK hospital study

Author

Boshier, Florencia A.T., Venturini, Cristina, Stirrup, Oliver, Guerra-Assunção, José Afonso, Alcolea-Medina, Adela, Becket, Angela H., Byott, Matthew, Charalampous, Themoula, Filipe, Ana da Silva, Frampton, Dan, Glaysher, Sharon, Khan, Tabassum, Kulasegara-Shylini, Raghavendran, Kele, Beatrix, Monahan, Irene M., Mollett, Guy, Parker, Matthew, Pelosi, Emanuela, Randell, Paul, Roy, Sunando, Taylor, Joshua F., Weller, Sophie J., Wilson-Davies, Eleri, Wade, Phillip, Williams, Rachel, Copas, Andrew J., Cutino-Moguel, Teresa, Freemantle, Nick, Hayward, Andrew C., Holmes, Alison, Hughes, Joseph, Mahungu, Tabitha W., Nebbia, Gaia, Nastouli, Eleni, Partridge, David G., Pope, Cassie F., Price, James R., Robson, Samuel C., Saeed, Kordo, Shin, Gee Yen, de Silva, Thushan I., Snell, Luke B., Thomson, Emma C., Witney, Adam A., Breuer, Judith, COG-UK HOCI Variant Substudy consortium, The COVID-19 Genomics UK (COG-UK) consortium, Bashton, Matthew, Nelson, Andrew, McCann, Clare, Smith, Darren, and Young, Greg

Subjects
Microbiology (medical), medicine.medical_specialty, lineage B.1.1.7, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), B100, Alpha (ethology), variants of concern, Logistic regression, Article, Internal medicine, Epidemiology, medicine, Humans, transmissibility, Infection control, nosocomial outbreaks, Cross Infection, Nosocomial outbreak, SARS-CoV-2, business.industry, Transmission (medicine), COVID-19, Outbreak, C500, C700, Hospitals, United Kingdom, Infectious Diseases, Alpha variant, business
Abstract

Objectives : Recently emerging SARS-CoV-2 variants have been associated with an increased rate of transmission within the community. We sought to determine whether this also resulted in increased transmission within hospitals. Methods : We collected viral sequences and epidemiological data of patients with community and healthcare associated SARS-CoV-2 infections, sampled from 16th November 2020 to 10th January 2021, from nine hospitals participating in the COG-UK HOCI study. Outbreaks were identified using ward information, lineage and pairwise genetic differences between viral sequences. Results : Mixed effects logistic regression analysis of 4184 sequences showed healthcare-acquired infections were no more likely to be identified as the Alpha variant than community acquired infections. Nosocomial outbreaks were investigated based on overlapping ward stay and SARS-CoV-2 genome sequence similarity. There was no significant difference in the number of patients involved in outbreaks caused by the Alpha variant compared to outbreaks caused by other lineages. Conclusions : We find no evidence to support it causing more nosocomial transmission than previous lineages. This suggests that the stringent infection prevention measures already in place in UK hospitals contained the spread of the Alpha variant as effectively as other less transmissible lineages, providing reassurance of their efficacy against emerging variants of concern. 40 word summary: This UK multicentre study found no evidence to support the Alpha variant as having caused more nosocomial transmission that previous SARS-CoV-2 variants. This provides some reassurance that currently implemented IPC measures may be as effective against more transmissible variants.

Published
2021

6. The Alpha variant was not associated with excess nosocomial SARS-CoV-2 infection in a multi-centre UK hospital study

Author

Boshier, Florencia AT, Venturini, Cristina, Stirrup, Oliver, Guerra-Assunção, José Afonso, Alcolea-Medina, Adela, Becket, Angela H, Byott, Matthew, Charalampous, Themoula, Filipe, Ana Da Silva, Frampton, Dan, Glaysher, Sharon, Khan, Tabassum, Kulasegara-Shylini, Raghavendran, Kele, Beatrix, Monahan, Irene M, Mollett, Guy, Parker, Matthew, Pelosi, Emanuela, Randell, Paul, Roy, Sunando, Taylor, Joshua F, Weller, Sophie J, Wilson-Davies, Eleri, Wade, Phillip, Williams, Rachel, Copas, Andrew J, Cutino-Moguel, Teresa, Freemantle, Nick, Hayward, Andrew C, Holmes, Alison, Hughes, Joseph, Mahungu, Tabitha W, Nebbia, Gaia, Nastouli, Eleni, Partridge, David G, Pope, Cassie F, Price, James R, Robson, Samuel C, Saeed, Kordo, Shin, Gee Yen, De Silva, Thushan I, Snell, Luke B, Thomson, Emma C, Witney, Adam A, Breuer, Judith, COG-UK HOCI Variant Substudy Consortium*, The COVID-19 Genomics UK (COG-UK) Consortium, Venturini, Cristina [0000-0002-4769-7912], Copas, Andrew J [0000-0001-8968-5963], Robson, Samuel C [0000-0001-5702-9160], Breuer, Judith [0000-0001-8246-0534], and Apollo - University of Cambridge Repository

Subjects
Variants of concern, Cross Infection, Alpha variant, SARS-CoV-2, Transmissibility, COVID-19, Humans, Lineage B.1.1.7, Nosocomial outbreaks, Hospitals, United Kingdom
Abstract

OBJECTIVES: Recently emerging SARS-CoV-2 variants have been associated with an increased rate of transmission within the community. We sought to determine whether this also resulted in increased transmission within hospitals. METHODS: We collected viral sequences and epidemiological data of patients with community and healthcare associated SARS-CoV-2 infections, sampled from 16th November 2020 to 10th January 2021, from nine hospitals participating in the COG-UK HOCI study. Outbreaks were identified using ward information, lineage and pairwise genetic differences between viral sequences. RESULTS: Mixed effects logistic regression analysis of 4184 sequences showed healthcare-acquired infections were no more likely to be identified as the Alpha variant than community acquired infections. Nosocomial outbreaks were investigated based on overlapping ward stay and SARS-CoV-2 genome sequence similarity. There was no significant difference in the number of patients involved in outbreaks caused by the Alpha variant compared to outbreaks caused by other lineages. CONCLUSIONS: We find no evidence to support it causing more nosocomial transmission than previous lineages. This suggests that the stringent infection prevention measures already in place in UK hospitals contained the spread of the Alpha variant as effectively as other less transmissible lineages, providing reassurance of their efficacy against emerging variants of concern.

Published
2021

7. 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

8. 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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9. Prior SARS-CoV-2 infection rescues B and T cell responses to variants after first vaccine dose

Author

Reynolds, Catherine J., Pade, Corinna, Gibbons, Joseph M., Butler, David K., Otter, Ashley D., Menacho, Katia, Fontana, Marianna, Smit, Angelique, Sackville-West, Jane E., Cutino-Moguel, Teresa, Maini, Mala K., Chain, Benjamin, Noursadeghi, Mahdad, Brooks, Tim, Semper, Amanda, Manisty, Charlotte, Treibel, Thomas A., Moon, James C., Valdes, Ana M., Altmann, Daniel M., Boyton, Rosemary, UK COVIDsortium Immune Correlates Network, and UK COVIDsortium Investigators

Abstract

SARS-CoV-2 vaccine rollout has coincided with the spread of variants of concern. We investigated if single dose vaccination, with or without prior infection, confers cross protective immunity to variants. We analyzed T and B cell responses after first dose vaccination with the Pfizer/BioNTech mRNA vaccine BNT162b2 in healthcare workers (HCW) followed longitudinally, with or without prior Wuhan-Hu-1 SARS-CoV-2 infection. After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 and B.1.351. By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 and B.1.351 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Single dose vaccination with BNT162b2 in the context of prior infection with a heterologous variant substantially enhances neutralizing antibody responses against variants.

Published
2021

10. Disparities of SARS-CoV-2 Nucleoprotein-Specific IgG in Healthcare Workers in East London, UK

Author

Choudhry, Naheed, primary, Drysdale, Kate, additional, Usai, Carla, additional, Leighton, Dean, additional, Sonagara, Vinay, additional, Buchanan, Ruaridh, additional, Nijjar, Manreet, additional, Thomas, Sherine, additional, Hopkins, Mark, additional, Cutino-Moguel, Teresa, additional, Gill, Upkar S., additional, Foster, Graham R., additional, and Kennedy, Patrick T., additional

Published
2021
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11. Persistence of antibody response to SARS-CoV-2 in a cohort of haemodialysis patients with COVID-19

Author

Forbes, Suzanne, primary, Davari, Maria, additional, Gnanasampanthan, Sahana, additional, Roth, Noam, additional, Young, Gregor, additional, Rajakariar, Ravindra, additional, Cove-Smith, Andrea, additional, Yaqoob, Muhammed Magdi, additional, Cutino-Moguel, Teresa, additional, Mahalingasivam, Viyaasan, additional, and McCafferty, Kieran, additional

Published
2021
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12. Time series analysis and mechanistic modelling of heterogeneity and sero-reversion in antibody responses to mild SARS‑CoV-2 infection

Author

Manisty, Charlotte, primary, Treibel, Thomas Alexander, additional, Jensen, Melanie, additional, Semper, Amanda, additional, Joy, George, additional, Gupta, Rishi K, additional, Cutino-Moguel, Teresa, additional, Andiapen, Mervyn, additional, Jones, Jessica, additional, Taylor, Stephen, additional, Otter, Ashley, additional, Pade, Corrina, additional, Gibbons, Joseph, additional, Lee, Jason, additional, Bacon, Joanna, additional, Thomas, Steve, additional, Moon, Chris, additional, Jones, Meleri, additional, Williams, Dylan, additional, Lambourne, Jonathan, additional, Fontana, Marianna, additional, Altmann, Daniel M, additional, Boyton, Rosemary, additional, Maini, Mala, additional, McKnight, Aine, additional, Chain, Benjamin, additional, Noursadeghi, Mahdad, additional, and Moon, James C, additional

Published
2021
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13. Healthcare Workers Bioresource: Study outline and baseline characteristics of a prospective healthcare worker cohort to study immune protection and pathogenesis in COVID-19

Author

Augusto, João B, primary, Menacho, Katia, additional, Andiapen, Mervyn, additional, Bowles, Ruth, additional, Burton, Maudrian, additional, Welch, Sophie, additional, Bhuva, Anish N, additional, Seraphim, Andreas, additional, Pade, Corinna, additional, Joy, George, additional, Jensen, Melanie, additional, Davies, Rhodri H, additional, Captur, Gabriella, additional, Fontana, Marianna, additional, Montgomery, Hugh, additional, O’Brien, Ben, additional, Hingorani, Aroon D, additional, Cutino-Moguel, Teresa, additional, McKnight, Áine, additional, Abbass, Hakam, additional, Alfarih, Mashael, additional, Alldis, Zoe, additional, Baca, Georgina L, additional, Boulter, Alex, additional, Bracken, Olivia V, additional, Bullock, Natalie, additional, Champion, Nicola, additional, Chan, Carmen, additional, Couto-Parada, Xose, additional, Dieobi-Anene, Keenan, additional, Feehan, Karen, additional, Figtree, Gemma, additional, Figtree, Melanie C, additional, Finlay, Malcolm, additional, Forooghi, Nasim, additional, Gibbons, Joseph M, additional, Griffiths, Peter, additional, Hamblin, Matt, additional, Howes, Lee, additional, Itua, Ivie, additional, Jones, Meleri, additional, Jardim, Victor, additional, Kapil, Vikas, additional, Jason Lee, Wing-Yiu, additional, Mandadapu, Vineela, additional, Mfuko, Celina, additional, Mitchelmore, Oliver, additional, Palma, Susana, additional, Patel, Kush, additional, Petersen, Steffen E, additional, Piniera, Brian, additional, Raine, Rosalind, additional, Rapala, Alicja, additional, Richards, Amy, additional, Sambile, Genine, additional, Couto de Sousa, Jorge, additional, Sugimoto, Michelle, additional, Thornton, George D, additional, Artico, Jessica, additional, Zahedi, Dan, additional, Parker, Ruth, additional, Robathan, Mathew, additional, Hickling, Lauren M, additional, Ntusi, Ntobeko, additional, Semper, Amanda, additional, Brooks, Tim, additional, Jones, Jessica, additional, Tucker, Art, additional, Veerapen, Jessry, additional, Vijayakumar, Mohit, additional, Wodehouse, Theresa, additional, Wynne, Lucinda, additional, Treibel, Thomas A, additional, Noursadeghi, Mahdad, additional, Manisty, Charlotte, additional, and Moon, James C, additional

Published
2020
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14. 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, 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, Moon, James C., Mills, Kevin, and Heywood, Wendy E.

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
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