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3. The antigenic anatomy of SARS-CoV-2 receptor binding domain

Author

Dejnirattisai, Wanwisa, Zhou, Daming, Ginn, Helen M., Duyvesteyn, Helen M.E., Supasa, Piyada, Case, James Brett, Zhao, Yuguang, Walter, Thomas S., Mentzer, Alexander J., Liu, Chang, Wang, Beibei, Paesen, Guido C., Slon-Campos, Jose, López-Camacho, César, Kafai, Natasha M., Bailey, Adam L., Chen, Rita E., Ying, Baoling, Thompson, Craig, Bolton, Jai, Fyfe, Alex, Gupta, Sunetra, Tan, Tiong Kit, Gilbert-Jaramillo, Javier, James, William, Knight, Michael, Carroll, Miles W., Skelly, Donal, Dold, Christina, Peng, Yanchun, Levin, Robert, Dong, Tao, Pollard, Andrew J., Knight, Julian C., Klenerman, Paul, Temperton, Nigel, Hall, David R., Williams, Mark A., Paterson, Neil G., Bertram, Felicity K.R., Siebert, C. Alistair, Clare, Daniel K., Howe, Andrew, Radecke, Julika, Song, Yun, Townsend, Alain R., Huang, Kuan-Ying A., Fry, Elizabeth E., Mongkolsapaya, Juthathip, Diamond, Michael S., Ren, Jingshan, Stuart, David I., and Screaton, Gavin R.

Published
2021
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5. Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

Author

McNaughton, Anna L, Paton, Robert S, Edmans, Matthew, Youngs, Jonathan, Wellens, Judith, Phalora, Prabhjeet, Fyfe, Alex, Belij-Rammerstorfer, Sandra, Bolton, Jai S, Ball, Jonathan, Carnell, George W, Dejnirattisai, Wanwisa, Dold, Christina, Eyre, David W, Hopkins, Philip, Howarth, Alison, Kooblall, Kreepa, Klim, Hannah, Leaver, Susannah, Lee, Lian Ni, López-Camacho, César, Lumley, Sheila F, Macallan, Derek C, Mentzer, Alexander J, Provine, Nicholas M, Ratcliff, Jeremy, Slon-Compos, Jose, Skelly, Donal, Stolle, Lucas, Supasa, Piyada, Temperton, Nigel, Walker, Chris, Wang, Beibei, Wyncoll, Duncan, Oxford Protective T Cell Immunology for COVID-19 (OPTIC) consortium, Scottish National Blood Transfusion Service (SNBTS) consortium, Simmonds, Peter, Lambe, Teresa, Baillie, John Kenneth, Semple, Malcolm G, Openshaw, Peter Jm, International Severe Acute Respiratory and emerging Infection Consortium Coronavirus Clinical Characterisation Consortium (ISARIC4C) investigators, Obolski, Uri, Turner, Marc, Carroll, Miles, Mongkolsapaya, Juthathip, Screaton, Gavin, Kennedy, Stephen H, Jarvis, Lisa, Barnes, Eleanor, Dunachie, Susanna, Lourenço, José, Matthews, Philippa C, Bicanic, Tihana, Klenerman, Paul, Gupta, Sunetra, Thompson, Craig P, Carnell, George [0000-0001-8875-0989], and Apollo - University of Cambridge Repository

Subjects
Infectious disease, Epitopes, SARS-CoV-2, FOS: Clinical medicine, Adaptive immunity, Immunology, Antibody Formation, Spike Glycoprotein, Coronavirus, COVID-19, Humans, Imprinting, Antibodies, Viral
Abstract

The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal outcomes with coronavirus disease 2019 (COVID-19) is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to an intensive care unit (ICU) with fatal COVID-19 outcomes, but not in individuals with nonfatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to an ICU with fatal and nonfatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an "original antigenic sin" type response.

Published
2022
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6. Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

Author

McNaughton, Anna L., primary, Paton, Robert S., additional, Edmans, Matthew, additional, Youngs, Jonathan, additional, Wellens, Judith, additional, Phalora, Prabhjeet, additional, Fyfe, Alex, additional, Belij-Rammerstorfer, Sandra, additional, Bolton, Jai S., additional, Ball, Jonathan, additional, Carnell, George W., additional, Dejnirattisai, Wanwisa, additional, Dold, Christina, additional, Eyre, David W., additional, Hopkins, Philip, additional, Howarth, Alison, additional, Kooblall, Kreepa, additional, Klim, Hannah, additional, Leaver, Susannah, additional, Lee, Lian Ni, additional, López-Camacho, César, additional, Lumley, Sheila F., additional, Macallan, Derek C., additional, Mentzer, Alexander J., additional, Provine, Nicholas M., additional, Ratcliff, Jeremy, additional, Slon-Compos, Jose, additional, Skelly, Donal, additional, Stolle, Lucas, additional, Supasa, Piyada, additional, Temperton, Nigel, additional, Walker, Chris, additional, Wang, Beibei, additional, Wyncoll, Duncan, additional, Simmonds, Peter, additional, Lambe, Teresa, additional, Baillie, John Kenneth, additional, Semple, Malcolm G., additional, Openshaw, Peter J.M., additional, Obolski, Uri, additional, Turner, Marc, additional, Carroll, Miles, additional, Mongkolsapaya, Juthathip, additional, Screaton, Gavin, additional, Kennedy, Stephen H., additional, Jarvis, Lisa, additional, Barnes, Eleanor, additional, Dunachie, Susanna, additional, Lourenço, José, additional, Matthews, Philippa C., additional, Bicanic, Tihana, additional, Klenerman, Paul, additional, Gupta, Sunetra, additional, and Thompson, Craig P., additional

Published
2022
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7. Refining the welfare of immunocompromised mice receiving carbon tetrachloride (CCl4) to induce liver fibrosis.

Author

WALCZAK-GILLIES, VICKY, MATTHEWS, OLIVIA, FYFE, ALEX, HOY, ANNA, and LEWIS, PHILLIP STARKEY

Subjects
ANIMAL welfare, IMMUNOCOMPROMISED patients, CARBON tetrachloride, FIBROSIS, INTRAPERITONEAL injections
Abstract

This article discusses the refinement of the care and welfare of immunocompromised mice receiving carbon tetrachloride (CCl4) to induce liver fibrosis. The researchers implemented new dosing criteria and recovery techniques to enhance animal welfare while maintaining sufficient levels of fibrosis in the liver. The study found that these changes improved both animal welfare and scientific outputs, reducing the need to repeat studies and the overall number of animals required. The method can be easily adapted for any study, and the smallest actions can have a significant impact. [Extracted from the article]

Published
2023

8. Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

Author

McNaughton, Anna L., Paton, Robert S., Edmans, Matthew, Youngs, Jonathan C.W., Wellens, Judith, Phalora, Prabhjeet, Fyfe, Alex, Belij-Rammerstorfer, Sandra, Bolton, Jai S., Ball, Jonathan, Carnell, George W., Dejnirattisai, Wanwisa, Dold, Christina, Eyre, David W., Hopkins, Philip, Howarth, Alison, Kooblall, Kreepa, Klim, Hannah, Leaver, Susannah, Lee, Lian N., López-Camacho, César, Lumley, Sheila F., Macallan, Derek C., Mentzer, Alexander J., Provine, Nicholas M., Ratcliff, Jeremy, Slon-Campos, Jose L., Skelly, Donal T., Stolle, Lucas B., Supasa, Piyada, Temperton, Nigel J., Walker, Chris, Wang, Beibei, Wyncoll, Duncan, Simmonds, Peter, Lambe, Teresa, Ballie, John K., Semple, Malcolm G., Openshaw, Peter J.M., Obolski, Uri, Turner, Marc, Carroll, Miles, Mongkolsapaya, Juthathip, Screaton, Gavin, Kennedy, Stephen H., Jarvis, Lisa M., Barnes, Eleanor, Dunachie, Susanna, Lourenço, José, Matthews, Philippa C., Bicanic, Tihana, Klenerman, Paul, Gupta, Sunetra, Thompson, Craig P., McNaughton, Anna L., Paton, Robert S., Edmans, Matthew, Youngs, Jonathan C.W., Wellens, Judith, Phalora, Prabhjeet, Fyfe, Alex, Belij-Rammerstorfer, Sandra, Bolton, Jai S., Ball, Jonathan, Carnell, George W., Dejnirattisai, Wanwisa, Dold, Christina, Eyre, David W., Hopkins, Philip, Howarth, Alison, Kooblall, Kreepa, Klim, Hannah, Leaver, Susannah, Lee, Lian N., López-Camacho, César, Lumley, Sheila F., Macallan, Derek C., Mentzer, Alexander J., Provine, Nicholas M., Ratcliff, Jeremy, Slon-Campos, Jose L., Skelly, Donal T., Stolle, Lucas B., Supasa, Piyada, Temperton, Nigel J., Walker, Chris, Wang, Beibei, Wyncoll, Duncan, Simmonds, Peter, Lambe, Teresa, Ballie, John K., Semple, Malcolm G., Openshaw, Peter J.M., Obolski, Uri, Turner, Marc, Carroll, Miles, Mongkolsapaya, Juthathip, Screaton, Gavin, Kennedy, Stephen H., Jarvis, Lisa M., Barnes, Eleanor, Dunachie, Susanna, Lourenço, José, Matthews, Philippa C., Bicanic, Tihana, Klenerman, Paul, Gupta, Sunetra, and Thompson, Craig P.

Abstract

The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal coronavirus disease (COVID-19) outcomes is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses, and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to intensive care units (ICU) with fatal COVID-19 outcomes, but not in individuals with non-fatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to ICU with fatal and non-fatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an original antigenic sin type-response.

Published
2022

9. Fatal COVID-19 Outcomes are Associated with an Antibody Response Targeting Epitopes Shared with Endemic Coronaviruses

Author

McNaughton, Anna L., primary, Paton, Robert S., additional, Edmans, Matthew, additional, Youngs, Jonathan, additional, Wellens, Judith, additional, Phalora, Prabhjeet, additional, Fyfe, Alex, additional, Belij-rammerstorfer, Sandra, additional, Bolton, Jai S., additional, Ball, Jonathan, additional, Carnell, George, additional, Dejnirattisai, Wanwisa, additional, Dold, Christina, additional, Eyre, David W., additional, Hopkins, Philip, additional, Howarth, Alison, additional, Kooblall, Kreepa, additional, Klim, Hannah, additional, Leaver, Susannah, additional, Lee, Lian, additional, Lopez-Camacho, Cesar, additional, Lumley, Sheila, additional, Macallan, Derek, additional, Mentzer, Alexander J., additional, Provine, Nicholas, additional, Ratcliff, Jeremy, additional, Slon-Campos, Jose, additional, Skelly, Donal, additional, Stolle, Lucas, additional, Supasa, Piyada, additional, Temperton, Nigel, additional, Walker, Chris, additional, Wang, Beibei, additional, Wyncoll, Duncan, additional, consortium, OPTIC, additional, consortium, SNBTS, additional, Simmonds, Peter, additional, Lambe, Teresa, additional, Baillie, J. Kenneth, additional, Semple, Malcolm, additional, Openshaw, Peter, additional, Obolski, Uri, additional, Turner, Marc, additional, Carroll, Miles W., additional, Mongkolspaya, Juthathip, additional, Screaton, Gavin R., additional, Kennedy, Stephen H., additional, Jarvis, Lisa, additional, Barnes, Eleanor, additional, Dunachie, Susanna, additional, Lourenço, José, additional, Matthews, Philippa, additional, Bicanic, Tihana, additional, Klenerman, Paul, additional, Gupta, Sunetra, additional, and Thompson, Craig P., additional

Published
2021
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11. Convalescent plasma therapy for the treatment of patients with COVID‐19: Assessment of methods available for antibody detection and their correlation with neutralising antibody levels

Author

Harvala, Heli, primary, Robb, Matthew L., additional, Watkins, Nick, additional, Ijaz, Samreen, additional, Dicks, Steven, additional, Patel, Monika, additional, Supasa, Piyada, additional, Wanwisa, Dejnirattisai, additional, Liu, Chang, additional, Mongkolsapaya, Juthathip, additional, Bown, Abbie, additional, Bailey, Daniel, additional, Vipond, Richard, additional, Grayson, Nicholas, additional, Temperton, Nigel, additional, Gupta, Sunetra, additional, Ploeg, Rutger J., additional, Bolton, Jai, additional, Fyfe, Alex, additional, Gopal, Robin, additional, Simmonds, Peter, additional, Screaton, Gavin, additional, Thompson, Craig, additional, Brooks, Tim, additional, Zambon, Maria, additional, Miflin, Gail, additional, and Roberts, David J., additional

Published
2020
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12. Convalescent plasma therapy for the treatment of patients with COVID‐19: Assessment of methods available for antibody detection and their correlation with neutralising antibody levels

Author

Harvala, Heli, Robb, Matthew L., Watkins, Nick, Ijaz, Samreen, Dicks, Steven, Patel, Monika, Supasa, Piyada, Wanwisa, Dejnirattisai, Liu, Chang, Mongkolsapaya, Juthathip, Bown, Abbie, Bailey, Daniel, Vipond, Richard, Grayson, Nicholas, Temperton, Nigel, Gupta, Sunetra, Ploeg, Rutger J., Bolton, Jai, Fyfe, Alex, Gopal, Robin, Simmonds, Peter, Screaton, Gavin, Thompson, Craig, Brooks, Tim, Zambon, Maria, Miflin, Gail, Roberts, David J., Harvala, Heli, Robb, Matthew L., Watkins, Nick, Ijaz, Samreen, Dicks, Steven, Patel, Monika, Supasa, Piyada, Wanwisa, Dejnirattisai, Liu, Chang, Mongkolsapaya, Juthathip, Bown, Abbie, Bailey, Daniel, Vipond, Richard, Grayson, Nicholas, Temperton, Nigel, Gupta, Sunetra, Ploeg, Rutger J., Bolton, Jai, Fyfe, Alex, Gopal, Robin, Simmonds, Peter, Screaton, Gavin, Thompson, Craig, Brooks, Tim, Zambon, Maria, Miflin, Gail, and Roberts, David J.

Abstract

Introduction The lack of approved specific therapeutic agents to treat coronavirus disease (COVID‐19) associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has led to the rapid implementation of convalescent plasma therapy (CPT) trials in many countries, including the United Kingdom. Effective CPT is likely to require high titres of neutralising antibody (nAb) in convalescent donations. Understanding the relationship between functional neutralising antibodies and antibody levels to specific SARS‐CoV‐2 proteins in scalable assays will be crucial for the success of a large‐scale collection. We assessed whether neutralising antibody titres correlated with reactivity in a range of enzyme‐linked immunosorbent assays (ELISA) targeting the spike (S) protein, the main target for human immune response. Methods Blood samples were collected from 52 individuals with a previous laboratory‐confirmed SARS‐CoV‐2 infection. These were assayed for SARS‐CoV‐2 nAbs by microneutralisation and pseudo‐type assays and for antibodies by four different ELISAs. Receiver operating characteristic (ROC) analysis was used to further identify sensitivity and specificity of selected assays to identify samples containing high nAb levels. Results All samples contained SARS‐CoV‐2 antibodies, whereas neutralising antibody titres of greater than 1:20 were detected in 43 samples (83% of those tested) and >1:100 in 22 samples (42%). The best correlations were observed with EUROimmun immunoglobulin G (IgG) reactivity (Spearman Rho correlation coefficient 0.88; p < 0.001). Based on ROC analysis, EUROimmun would detect 60% of samples with titres of >1:100 with 100% specificity using a reactivity index of 9.1 (13/22). Discussion Robust associations between nAb titres and reactivity in several ELISA‐based antibody tests demonstrate their possible utility for scaled‐up production of convalescent plasma containing potentially therapeutic levels of anti‐SARS‐CoV‐2 nAbs.

Published
2020

13. Detection of neutralising antibodies to SARS-CoV-2 to determine population exposure in Scottish blood donors between March and May 2020

Author

Thompson, Craig P, Grayson, Nicholas E, Paton, Robert S, Bolton, Jai S, Lourenço, José, Penman, Bridget S, Lee, Lian N, Odon, Valerie, Mongkolsapaya, Juthathip, Chinnakannan, Senthil, Dejnirattisai, Wanwisa, Edmans, Matthew, Fyfe, Alex, Imlach, Carol, Kooblall, Kreepa, Lim, Nicholas, Liu, Chang, López-Camacho, César, McInally, Carol, McNaughton, Anna L, Ramamurthy, Narayan, Ratcliff, Jeremy, Supasa, Piyada, Sampson, Oliver, Wang, Beibei, Mentzer, Alexander J, Turner, Marc, Semple, Malcolm G, Baillie, Kenneth, Harvala, Heli, Screaton, Gavin R, Temperton, Nigel J., Klenerman, Paul, Jarvis, Lisa M, Gupta, Sunetra, Simmonds, Peter, Thompson, Craig P, Grayson, Nicholas E, Paton, Robert S, Bolton, Jai S, Lourenço, José, Penman, Bridget S, Lee, Lian N, Odon, Valerie, Mongkolsapaya, Juthathip, Chinnakannan, Senthil, Dejnirattisai, Wanwisa, Edmans, Matthew, Fyfe, Alex, Imlach, Carol, Kooblall, Kreepa, Lim, Nicholas, Liu, Chang, López-Camacho, César, McInally, Carol, McNaughton, Anna L, Ramamurthy, Narayan, Ratcliff, Jeremy, Supasa, Piyada, Sampson, Oliver, Wang, Beibei, Mentzer, Alexander J, Turner, Marc, Semple, Malcolm G, Baillie, Kenneth, Harvala, Heli, Screaton, Gavin R, Temperton, Nigel J., Klenerman, Paul, Jarvis, Lisa M, Gupta, Sunetra, and Simmonds, Peter

Abstract

BackgroundThe progression and geographical distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United Kingdom (UK) and elsewhere is unknown because typically only symptomatic individuals are diagnosed. We performed a serological study of blood donors in Scotland in the spring of 2020 to detect neutralising antibodies to SARS-CoV-2 as a marker of past infection and epidemic progression.AimOur objective was to determine if sera from blood bank donors can be used to track the emergence and progression of the SARS-CoV-2 epidemic.MethodsA pseudotyped SARS-CoV-2 virus microneutralisation assay was used to detect neutralising antibodies to SARS-CoV-2. The study comprised samples from 3,500 blood donors collected in Scotland between 17 March and 18 May 2020. Controls were collected from 100 donors in Scotland during 2019.ResultsAll samples collected on 17 March 2020 (n = 500) were negative in the pseudotyped SARS-CoV-2 virus microneutralisation assay. Neutralising antibodies were detected in six of 500 donors from 23 to 26 March. The number of samples containing neutralising antibodies did not significantly rise after 5-6 April until the end of the study on 18 May. We found that infections were concentrated in certain postcodes, indicating that outbreaks of infection were extremely localised. In contrast, other areas remained comparatively untouched by the epidemic.ConclusionAlthough blood donors are not representative of the overall population, we demonstrated that serosurveys of blood banks can serve as a useful tool for tracking the emergence and progression of an epidemic such as the SARS-CoV-2 outbreak.

Published
2020

16. ­­­The Antigenic Anatomy of SARS-CoV-2 Receptor Binding Domain

Author

Dejnirattisai, Wanwisa, primary, Zhou, Daming, additional, Ginn, Helen M., additional, Duyvesteyn, Helen ME, additional, Supasa, Piyada, additional, Case, James Brett, additional, Zhao, Yuguang, additional, Walter, Thomas S., additional, Mentzer, Alexander J., additional, Liu, Chang, additional, Wang, Beibei, additional, Paesen, Guido C., additional, Slon-Campos, Jose, additional, Lopez-Camacho, Cesar, additional, Kafai, Natasha M., additional, Bailey, Adam L., additional, Chen, Rita E., additional, Ying, Baoling, additional, Thompson, Craig P., additional, Fyfe, Alex, additional, Gupta, Sunetra, additional, Tan, Tiong, additional, Gilbert-Jaramillo, Javier, additional, James, William, additional, Buttigieg, Karen, additional, Coombes, Naomi, additional, Carroll, Miles W., additional, Skelly, Donal, additional, Dold, Christina, additional, Peng, Yanchun, additional, Levin, Robert, additional, Dong, Tao, additional, Pollard, Andrew, additional, Knight, Julian, additional, Klenerman, Paul, additional, Temperton, Nigel, additional, Hall, David R., additional, Williams, Mark A., additional, Paterson, Neil G., additional, Bertram, Felicity K.R., additional, Seibert, C. Alistair, additional, Clare, Daniel K., additional, Howe, Andrew, additional, Raedecke, Julika, additional, Song, Yun, additional, Townsend, Alain, additional, Huang, Kuan-Ying A., additional, Fry, Elizabeth E., additional, Mongkolspaya, Juthathip, additional, Diamond, Michael S., additional, Ren, Jingshan, additional, Stuart, David I., additional, and Screaton, Gavin R., additional

Published
2020
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17. Convalescent plasma therapy for the treatment of patients with COVID‐19: Assessment of methods available for antibody detection and their correlation with neutralising antibody levels.

Author

Harvala, Heli, Robb, Matthew L., Watkins, Nick, Ijaz, Samreen, Dicks, Steven, Patel, Monika, Supasa, Piyada, Wanwisa, Dejnirattisai, Liu, Chang, Mongkolsapaya, Juthathip, Bown, Abbie, Bailey, Daniel, Vipond, Richard, Grayson, Nicholas, Temperton, Nigel, Gupta, Sunetra, Ploeg, Rutger J., Bolton, Jai, Fyfe, Alex, and Gopal, Robin

Subjects
CONVALESCENT plasma, COVID-19, COVID-19 treatment, RANK correlation (Statistics), IMMUNOGLOBULIN G
Abstract

Introduction: The lack of approved specific therapeutic agents to treat coronavirus disease (COVID‐19) associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has led to the rapid implementation of convalescent plasma therapy (CPT) trials in many countries, including the United Kingdom. Effective CPT is likely to require high titres of neutralising antibody (nAb) in convalescent donations. Understanding the relationship between functional neutralising antibodies and antibody levels to specific SARS‐CoV‐2 proteins in scalable assays will be crucial for the success of a large‐scale collection. We assessed whether neutralising antibody titres correlated with reactivity in a range of enzyme‐linked immunosorbent assays (ELISA) targeting the spike (S) protein, the main target for human immune response. Methods: Blood samples were collected from 52 individuals with a previous laboratory‐confirmed SARS‐CoV‐2 infection. These were assayed for SARS‐CoV‐2 nAbs by microneutralisation and pseudo‐type assays and for antibodies by four different ELISAs. Receiver operating characteristic (ROC) analysis was used to further identify sensitivity and specificity of selected assays to identify samples containing high nAb levels. Results: All samples contained SARS‐CoV‐2 antibodies, whereas neutralising antibody titres of greater than 1:20 were detected in 43 samples (83% of those tested) and >1:100 in 22 samples (42%). The best correlations were observed with EUROimmun immunoglobulin G (IgG) reactivity (Spearman Rho correlation coefficient 0.88; p < 0.001). Based on ROC analysis, EUROimmun would detect 60% of samples with titres of >1:100 with 100% specificity using a reactivity index of 9.1 (13/22). Discussion Robust associations between nAb titres and reactivity in several ELISA‐based antibody tests demonstrate their possible utility for scaled‐up production of convalescent plasma containing potentially therapeutic levels of anti‐SARS‐CoV‐2 nAbs. [ABSTRACT FROM AUTHOR]

Published
2021
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20. Detection of neutralising antibodies to SARS-CoV-2 to determine population exposure in Scottish blood donors between March and May 2020.

Author

Thompson, Craig P., Grayson, Nicholas E., Paton, Robert S., Bolton, Jai S., Lourenço, José, Penman, Bridget S., Lee, Lian N., Odon, Valerie, Mongkolsapaya, Juthathip, Chinnakannan, Senthil, Dejnirattisai, Wanwisa, Edmans, Matthew, Fyfe, Alex, Imlach, Carol, Kooblall, Kreepa, Lim, Nicholas, Chang Liu, López-Camacho, César, McInally, Carol, and McNaughton, Anna L.

Published
2020
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21. Role of Activins in Hepcidin Regulation during Malaria

Author

Spottiswoode, Natasha, Armitage, Andrew E, Williams, Andrew R, Fyfe, Alex J, Biswas, Sumi, Hodgson, Susanne H, Llewellyn, David, Choudhary, Prateek, Draper, Simon J, Duffy, Patrick, and Drakesmith, Hal

Subjects
parasitic diseases, Journal Article
Abstract

Epidemiological observations have linked increased host iron with malaria susceptibility, and perturbed iron handling has been hypothesized to contribute to the potentially life threatening anemia that may accompany blood-stage malaria infection. To improve our understanding of these relationships, we examined the pathways involved in regulation of the master controller of iron metabolism, the hormone hepcidin, in malaria infection. We show that hepcidin upregulation in Plasmodium berghei murine malaria infection was accompanied by changes in expression of bone morphogenetic protein (BMP)/sons of mothers against decapentaplegic (SMAD) pathway target genes, a key pathway involved in hepcidin regulation. We therefore investigated known agonists of the BMP/SMAD pathway, and found that Bmp gene expression was not increased in infection. In contrast, activin B, which can signal through the BMP/SMAD pathway and has been associated with increased hepcidin during inflammation, was upregulated in the livers of Plasmodium berghei infected mice; hepatic activin B was also upregulated at peak parasitemia during infection with Plasmodium chabaudi Concentrations of the closely related protein activin A increased in parallel with hepcidin in serum from malaria-naïve volunteers infected in controlled human malaria infection (CHMI) clinical trials. However, antibody-mediated neutralization of activin activity during murine malaria infection did not affect hepcidin expression, suggesting that these proteins are unlikely to stimulate hepcidin upregulation directly. In conclusion, we present evidence that the BMP/SMAD signalling pathway is perturbed in malaria infection, but that activins, although raised in malaria infection, may not have a critical role in hepcidin upregulation in this setting.

Published
2017
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22. Role of Activins in Hepcidin Regulation during Malaria

Author

Spottiswoode, Natasha, primary, Armitage, Andrew E., additional, Williams, Andrew R., additional, Fyfe, Alex J., additional, Biswas, Sumi, additional, Hodgson, Susanne H., additional, Llewellyn, David, additional, Choudhary, Prateek, additional, Draper, Simon J., additional, Duffy, Patrick E., additional, and Drakesmith, Hal, additional

Published
2017
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25. Functional Characterization and Comparison of Plasmodium falciparumProteins as Targets of Transmission-blocking Antibodies*

Author

Nikolaeva, Daria, Illingworth, Joseph J., Miura, Kazutoyo, Alanine, Daniel G.W., Brian, Iona J., Li, Yuanyuan, Fyfe, Alex J., Da, Dari F., Cohuet, Anna, Long, Carole A., Draper, Simon J., and Biswas, Sumi

Abstract

The malaria agent Plasmodium falciparumcontinues to evade control efforts. Despite multiple datasets for the Plasmodiumsexual-stage transcriptome and proteome, there have been no rational screens to identify candidate antigens for transmission-blocking vaccine (TBV) development. We demonstrate the use of rational screens and comparative functional assessments in identifying proteins of the P. falciparumtransmission pathway and establishing a robust pre-clinical TBV pipeline.

Published
2020
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27. Enhancing immunogenicity and transmission-blocking activity of malaria vaccines by fusing Pfs25 to IMX313 multimerization technology

Author

Li, Yuanyuan, primary, Leneghan, Darren B., additional, Miura, Kazutoyo, additional, Nikolaeva, Daria, additional, Brian, Iona J., additional, Dicks, Matthew D. J., additional, Fyfe, Alex J., additional, Zakutansky, Sarah E., additional, de Cassan, Simone, additional, Long, Carole A., additional, Draper, Simon J., additional, Hill, Adrian V. S., additional, Hill, Fergal, additional, and Biswas, Sumi, additional

Published
2016
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35. Detection of neutralising antibodies to SARS-CoV-2 to determine population exposure in Scottish blood donors between March and May 2020.

Author

Thompson CP, Grayson NE, Paton RS, Bolton JS, Lourenço J, Penman BS, Lee LN, Odon V, Mongkolsapaya J, Chinnakannan S, Dejnirattisai W, Edmans M, Fyfe A, Imlach C, Kooblall K, Lim N, Liu C, López-Camacho C, McInally C, McNaughton AL, Ramamurthy N, Ratcliff J, Supasa P, Sampson O, Wang B, Mentzer AJ, Turner M, Semple MG, Baillie K, Harvala H, Screaton GR, Temperton N, Klenerman P, Jarvis LM, Gupta S, and Simmonds P

Subjects
Adult, COVID-19, Cluster Analysis, Coronavirus Infections blood, Enzyme-Linked Immunosorbent Assay, Female, Geography, Medical, Humans, Inhibitory Concentration 50, Male, Models, Immunological, Neutralization Tests, Pneumonia, Viral blood, Prevalence, SARS-CoV-2, Scotland epidemiology, Sensitivity and Specificity, Seroepidemiologic Studies, Urban Population, Antibodies, Neutralizing blood, Antibodies, Viral blood, Betacoronavirus immunology, Blood Donors, Coronavirus Infections epidemiology, Pandemics, Pneumonia, Viral epidemiology, Population Surveillance
Abstract

BackgroundThe progression and geographical distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United Kingdom (UK) and elsewhere is unknown because typically only symptomatic individuals are diagnosed. We performed a serological study of blood donors in Scotland in the spring of 2020 to detect neutralising antibodies to SARS-CoV-2 as a marker of past infection and epidemic progression.AimOur objective was to determine if sera from blood bank donors can be used to track the emergence and progression of the SARS-CoV-2 epidemic.MethodsA pseudotyped SARS-CoV-2 virus microneutralisation assay was used to detect neutralising antibodies to SARS-CoV-2. The study comprised samples from 3,500 blood donors collected in Scotland between 17 March and 18 May 2020. Controls were collected from 100 donors in Scotland during 2019.ResultsAll samples collected on 17 March 2020 (n = 500) were negative in the pseudotyped SARS-CoV-2 virus microneutralisation assay. Neutralising antibodies were detected in six of 500 donors from 23 to 26 March. The number of samples containing neutralising antibodies did not significantly rise after 5-6 April until the end of the study on 18 May. We found that infections were concentrated in certain postcodes, indicating that outbreaks of infection were extremely localised. In contrast, other areas remained comparatively untouched by the epidemic.ConclusionAlthough blood donors are not representative of the overall population, we demonstrated that serosurveys of blood banks can serve as a useful tool for tracking the emergence and progression of an epidemic such as the SARS-CoV-2 outbreak.

Published
2020
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