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1. Post-resolution macrophages shape long-term tissue immunity and integrity in a mouse model of pneumococcal pneumonia

Author

Feehan, Karen T., Bridgewater, Hannah E., Stenkiewicz-Witeska, Jan, De Maeyer, Roel P. H., Ferguson, John, Mack, Matthias, Brown, Jeremy, Ercoli, Giuseppe, Mawer, Connar M., Akbar, Arne N., Glanville, James R. W., Jalali, Parinaaz, Bracken, Olivia V., Nicolaou, Anna, Kendall, Alexandra C., Sugimoto, Michelle A., and Gilroy, Derek W.

Published
2024
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3. 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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4. 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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6. Mediators of Inflammation

Author

Galvão, Izabela, Sugimoto, Michelle A., Vago, Juliana P., Machado, Marina G., Sousa, Lirlândia P., Riccardi, Carlo, editor, Levi-Schaffer, Francesca, editor, and Tiligada, Ekaterini, editor

Published
2018
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9. Intestinal toxicity evaluation of long-circulating and pH-sensitive liposomes loaded with cisplatin

Author

Araújo, Raquel Silva, Silveira, Ana Letícia Malheiros, de Sales e Souza, Éricka Lorenna, Freire, Rachel Horta, de Souza, Cristina Maria, Reis, Diego Carlos, Costa, Bruno Rocha Cordeiro, Sugimoto, Michelle Amantéa, Silveira, Josianne Nicácio, dos Santos Martins, Flaviano, Cassali, Geovanni Dantas, Leite, Jacqueline Isaura Alvarez, Sousa, Lirlândia Pires, Ferreira, Adaliene Versiani Matos, Oliveira, Mônica Cristina, and Cardoso, Valbert Nascimento

Published
2017
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10. Plasmin and plasminogen induce macrophage reprogramming and regulate key steps of inflammation resolution via annexin A1

Author

Sugimoto, Michelle A., Ribeiro, Ana Luíza C., Costa, Bruno R.C., Vago, Juliana P., Lima, Kátia M., Carneiro, Fernanda S., Ortiz, Mylena Maira O., Lima, Graziele Letícia N., Carmo, Aline A.F., Rocha, Renata M., Perez, Denise A., Reis, Alessandra C., Pinho, Vanessa, Miles, Lindsey A., Garcia, Cristiana C., Teixeira, Mauro M., and Sousa, Lirlândia P.

Published
2017
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11. In-depth characterization of a novel live-attenuated Mayaro virus vaccine candidate using an immunocompetent mouse model of Mayaro disease

Author

Mota, Mânlio Tasso de Oliveira, Costa, Vivian Vasconcelos, Sugimoto, Michelle Amantéa, Guimarães, Georgia de Freitas, Queiroz-Junior, Celso Martins, Moreira, Thaiane Pinto, de Sousa, Carla Daiane, Santos, Franciele Martins, Queiroz, Victoria Fulgêncio, Passos, Ingredy, Hubner, Josy, Souza, Danielle Gloria, Weaver, Scott C., Teixeira, Mauro Martins, and Nogueira, Maurício Lacerda

Published
2020
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14. Plasmin and plasminogen prevent sepsis severity by reducing neutrophil extracellular traps and systemic inflammation

Author

Vago, Juliana P., primary, Zaidan, Isabella, additional, Perucci, Luiza O., additional, Brito, Larissa F., additional, Teixeira, Lívia C.R., additional, Silva, Camila M.S., additional, Miranda, Thaís C., additional, Melo, Eliza M., additional, Bruno, Alexandre S., additional, Queiroz-Junior, Celso M., additional, Sugimoto, Michelle A., additional, Tavares, Luciana P., additional, Grossi, Laís C., additional, Borges, Isabela N., additional, Baik, Nagyung, additional, Talvani, André, additional, Ferreira, Raphael G., additional, Alves-Filho, José C., additional, Nobre, Vandack, additional, Teixeira, Mauro M., additional, Parmer, Robert J., additional, Miles, Lindsey A., additional, and Sousa, Lirlândia P., additional

Published
2023
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17. Post-resolution macrophage-derived lipids shapes long-term tissue immunity and integrity

Author

Feehan, Karen, primary, Bridgewater, Hannah, additional, Stenkiewicz-Witeska, Jan, additional, Ferguson, John, additional, Mack, Matthias, additional, BROWN, JEREMY, additional, Ercoli, Giuseppe, additional, Mawer, Connar, additional, Akbar, Arne, additional, Jalali, Parinaaz, additional, Bracken, Olivia, additional, Glanville, James, additional, Nicolaou, Anna, additional, Kendall, Alexandra, additional, Sugimoto, Michelle, additional, and Gilroy, Derek, additional

Published
2022
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18. 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

19. Annexin A1-FPR2/ALX Signaling Axis Regulates Acute Inflammation during Chikungunya Virus Infection

Author

de Araújo, Simone, primary, de Melo Costa, Victor R., additional, Santos, Franciele M., additional, de Sousa, Carla D. Ferreira, additional, Moreira, Thaiane P., additional, Gonçalves, Matheus R., additional, Félix, Franciel B., additional, Queiroz-Junior, Celso M., additional, Campolina-Silva, Gabriel H., additional, Nogueira, Maurício Lacerda, additional, Sugimoto, Michelle A., additional, Bonilha, Caio S., additional, Perretti, Mauro, additional, Souza, Danielle G., additional, Costa, Vivian V., additional, and Teixeira, Mauro M., additional

Published
2022
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20. 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

21. Targeting the Annexin A1-FPR2/ALX pathway for host-directed therapy in dengue disease

Author

Costa, Vivian Vasconcelos, primary, Sugimoto, Michelle A, primary, Hubner, Josy, additional, Bonilha, Caio S, additional, Queiroz-Junior, Celso Martins, additional, Gonçalves-Pereira, Marcela Helena, additional, Chen, Jianmin, additional, Gobbetti, Thomas, additional, Libanio Rodrigues, Gisele Olinto, additional, Bambirra, Jordana L, additional, Passos, Ingredy B, additional, Machado Lopes, Carla Elizabeth, additional, Moreira, Thaiane P, additional, Bonjour, Kennedy, additional, Melo, Rossana CN, additional, Oliveira, Milton AP, additional, Andrade, Marcus Vinicius M, additional, Sousa, Lirlândia Pires, additional, Souza, Danielle Gloria, additional, Santiago, Helton da Costa, additional, Perretti, Mauro, additional, and Teixeira, Mauro Martins, additional

Published
2022
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22. Author response: Targeting the Annexin A1-FPR2/ALX pathway for host-directed therapy in dengue disease

Author

Costa, Vivian Vasconcelos, primary, Sugimoto, Michelle A, primary, Hubner, Josy, additional, Bonilha, Caio S, additional, Queiroz-Junior, Celso Martins, additional, Gonçalves-Pereira, Marcela Helena, additional, Chen, Jianmin, additional, Gobbetti, Thomas, additional, Libanio Rodrigues, Gisele Olinto, additional, Bambirra, Jordana L, additional, Passos, Ingredy B, additional, Machado Lopes, Carla Elizabeth, additional, Moreira, Thaiane P, additional, Bonjour, Kennedy, additional, Melo, Rossana CN, additional, Oliveira, Milton AP, additional, Andrade, Marcus Vinicius M, additional, Sousa, Lirlândia Pires, additional, Souza, Danielle Gloria, additional, Santiago, Helton da Costa, additional, Perretti, Mauro, additional, and Teixeira, Mauro Martins, additional

Published
2022
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23. Angiotensin-(1-7)/MasR axis promotes migration of monocytes/macrophages with a regulatory phenotype to perform phagocytosis and efferocytosis

Author

Zaidan, Isabella, primary, Tavares, Luciana P., additional, Sugimoto, Michelle A., additional, Lima, Kátia M., additional, Negreiros-Lima, Graziele L., additional, Teixeira, Lívia C.R., additional, Miranda, Thais C., additional, Valiate, Bruno V.S., additional, Cramer, Allysson, additional, Vago, Juliana Priscila, additional, Campolina-Silva, Gabriel H., additional, Souza, Jéssica A.M., additional, Grossi, Laís C., additional, Pinho, Vanessa, additional, Campagnole-Santos, Maria Jose, additional, Santos, Robson A.S., additional, Teixeira, Mauro M., additional, Galvão, Izabela, additional, and Sousa, Lirlândia P., additional

Published
2022
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24. 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

26. Targeting the Annexin A1-FPR2/ALX pathway for host-directed therapy in dengue disease

Author

Costa, Vivian V, primary, Sugimoto, Michelle A, additional, Hubner, Josy, additional, Bonilha, Caio S, additional, Queiroz-Junior, Celso M, additional, Gonçalves Pereira, Marcela Helena, additional, Chen, Jianmin, additional, Gobbetti, Thomas, additional, Libanio Rodrigues, Gisele Olinto, additional, Bambirra, Jordana L., additional, Passos, Ingredy, additional, Machado Lopes, Carla Elizabeth, additional, Moreira, Thaiane P., additional, Bonjour, Kennedy, additional, Melo, Rossana C. N., additional, Oliveira, Milton A. P., additional, Andrade, Marcus Vinicius M., additional, Sousa, Lirlândia Pires, additional, Souza, Danielle Gloria, additional, Costa Santiago, Helton da, additional, Perretti, Mauro, additional, and Teixeira, Mauro Martins, additional

Published
2021
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27. 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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29. 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

30. Synthesis, Characterization and in vitro, in vivo and in silico Anti-Inflammatory Studies of the Novel Hybrid Based on Ibuprofen and 3-Hydroxy-Copalic Acid Isolated from Copaiba Oil (Copaifera multijuga)

Author

Souza,Fábio C. de, Brito,Larissa F., Silva,Marcos T., Sugimoto,Michelle A., Pinto,Ana Cristina S., Almeida,Patrícia D. O. de, Souza,Rodrigo O. S., Costa,Renyer A., Guilhon-Simplicio,Fernanda, Wanderley,Almir G., Oliveira,Kelson M. T. de, Sousa,Lirlândia P., Veiga-Junior,Valdir F. da, and Lima,Emerson S.

Subjects
Amazonia, 3-hydroxy-copalic acid, anti-inflammatory action, copaiba, ibuprofen
Abstract

A novel anti-inflammatory hybrid 3-ibuprofenyl-copalic acid (3-IbuCA) was synthesized from 3-hydroxy-copalic acid isolated from Amazonian copaiba oil (Copaifera multijuga Hayne), and the anti-inflammatory ibuprofen. After full characterization, several assays to verify its anti-inflammatory effects were performed in vitro, in vivo and in silico (molecular docking). Induced fit docking was performed to observe the interactions with the enzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). In vitro tests of cytotoxicity and tumor necrosis factor (TNF)-α inhibition, and in vivo tests of pleurisy, protein expression and gastrocytotoxicity were performed. Molecular docking studies with COX-1 and 2 showed binding free energies (ΔG) of -2.2 and -7.8 kcal mol-1, respectively, while for mofezolac and indomethacin, the binding free energies ΔG presented values of -8.5 and -10.1 kcal mol-1, which makes 3-IbuCA selective for COX-2 inhibition. This hybrid showed no toxicity against human macrophage at concentrations up to 2 µM, and inhibited TNF-α production in lipopolysaccharide (LPS)-stimulated macrophages. In the pleurisy assays, 3-IbuCA reduced the total leukocytes and mononuclear cells, which was followed by reduction of p-IKBα (phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha) protein expression. Compared with ibuprofen alone, the hybrid caused less gastric damage. Thus, the docking, together with in vitro and in vivo studies suggest that this novel hybrid has potential as a new anti-inflammatory agent.

Published
2020

32. Targeting the Annexin A1-FPR2/ALX pathway for host-directed therapy in dengue disease.

Author

Vasconcelos Costa, Vivian, Sugimoto, Michelle A., Hubner, Josy, Bonilha, Caio S., Martins Queiroz-Junior, Celso, Gonçalves-Pereira, Marcela Helena, Jianmin Chen, Gobbetti, Thomas, Olinto Libanio Rodrigues, Gisele, Bambirra, Jordana L., Passos, Ingredy B., Machado Lopes, Carla Elizabeth, Moreira, Thaiane P., Bonjour, Kennedy, Melo, Rossana C. N., Oliveira, Milton A. P., Andrade, Marcus Vinicius M., Pires Sousa, Lirlândia, Souza, Danielle Gloria, and da Costa Santiago, Helton

Subjects
*ANNEXINS, *DENGUE, *DENGUE viruses, *KNOCKOUT mice, *PEPTIDES, *PEPTIDE receptors, *SYMPTOMS, *ARBOVIRUS diseases
Abstract

Host immune responses contribute to dengue's pathogenesis and severity, yet the possibility that failure in endogenous inflammation resolution pathways could characterise the disease has not been contemplated. The pro-resolving protein Annexin A1 (AnxA1) is known to counterbalance overexuberant inflammation and mast cell (MC) activation. We hypothesised that inadequate AnxA1 engagement underlies the cytokine storm and vascular pathologies associated with dengue disease. Levels of AnxA1 were examined in the plasma of dengue patients and infected mice. Immunocompetent, interferon (alpha and beta) receptor one knockout (KO), AnxA1 KO, and formyl peptide receptor 2 (FPR2) KO mice were infected with dengue virus (DENV) and treated with the AnxA1 mimetic peptide Ac2-26 for analysis. In addition, the effect of Ac2-26 on DENV-induced MC degranulation was assessed in vitro and in vivo. We observed that circulating levels of AnxA1 were reduced in dengue patients and DENV-infected mice. Whilst the absence of AnxA1 or its receptor FPR2 aggravated illness in infected mice, treatment with AnxA1 agonistic peptide attenuated disease manifestationsatteanuated the symptoms of the disease. Both clinical outcomes were attributed to modulation of DENV-mediated viral load-independent MC degranulation. We have thereby identified that altered levels of the pro-resolving mediator AnxA1 are of pathological relevance in DENV infection, suggesting FPR2/ALX agonists as a therapeutic target for dengue disease. [ABSTRACT FROM AUTHOR]

Published
2022
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33. The Role of Plasmin/Plasminogen in Experimental Polymicrobial Sepsis

Author

Vago, Juliana, primary, Brito, Larissa Froede, additional, Teixeira, Lívia C.R., additional, Moreira, Izabela Z., additional, Miranda, Thaís C., additional, Melo, Eliza M., additional, Bruno, Alexandre S., additional, Sugimoto, Michelle A., additional, Ferreira, Raphael G., additional, Alves-Filho, Jose C., additional, Teixeira, Mauro M., additional, Parmer, Robert J, additional, Miles, Lindsey A, additional, and Sousa, Lirlandia P., additional

Published
2020
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34. 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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37. Glucocorticoid-induced leucine zipper modulates macrophage polarization and apoptotic cell clearance

Author

Vago, Juliana P., primary, Galvão, Izabela, additional, Negreiros-Lima, Graziele L., additional, Teixeira, Lívia C.R., additional, Lima, Kátia M., additional, Sugimoto, Michelle A., additional, Moreira, Isabella Z., additional, Jones, Sarah A., additional, Lang, Tali, additional, Riccardi, Carlo, additional, Teixeira, Mauro M., additional, Harris, James, additional, Morand, Eric F., additional, and Sousa, Lirlândia P., additional

Published
2020
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38. Cyclic AMP Regulates Key Features of Macrophages via PKA: Recruitment, Reprogramming and Efferocytosis

Author

Negreiros-Lima, Graziele L., primary, Lima, Kátia M., additional, Moreira, Isabella Z., additional, Jardim, Bruna Lorrayne O., additional, Vago, Juliana P., additional, Galvão, Izabela, additional, Teixeira, Lívia Cristina R., additional, Pinho, Vanessa, additional, Teixeira, Mauro M., additional, Sugimoto, Michelle A., additional, and Sousa, Lirlândia P., additional

Published
2020
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39. Synthesis, Characterization and in vitro, in vivo and in silico Anti-Inflammatory Studies of the Novel Hybrid Based on Ibuprofen and 3-Hydroxy-Copalic Acid Isolated from Copaiba Oil (Copaifera multijuga)

Author

de Souza, Fábio, primary, Brito, Larissa, additional, Silva, Marcos, additional, Sugimoto, Michelle, additional, Pinto, Ana Cristina, additional, de Almeida, Patrícia, additional, Souza, Rodrigo, additional, Costa, Renyer, additional, Guilhon-Simplicio, Fernanda, additional, Wanderley, Almir, additional, de Oliveira, Kelson, additional, Sousa, Lirlândia, additional, da Veiga-Junior, Valdir, additional, and Lima, Emerson, additional

Published
2020
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40. Formyl Peptide Receptor Type 2 Deficiency in Myeloid Cells Amplifies Sepsis-Induced Cardiac Dysfunction

Author

Chen, Jianmin, Austin-Williams, Shani, O'Riordan, Caroline Elizabeth, Claria-Ribas, Pol, Sugimoto, Michelle A, Norling, Lucy V, Thiemermann, Christoph, and Perretti, Mauro

Abstract

Using a global formyl peptide receptor (Fpr) 2 knockout mouse colony, we have reported the modulatory properties of this pro-resolving receptor in polymicrobial sepsis. Herein, we have used a humanized FPR2 (hFPR2) mouse colony, bearing an intact or a selective receptor deficiency in myeloid cells to dwell on the cellular mechanisms. hFPR2 mice and myeloid cell-specific hFPR2 KO (KO) mice were subjected to cecal ligation and puncture (CLP)-induced polymicrobial sepsis. Compared with hFPR2 mice, CLP caused exacerbated cardiac dysfunction (assessed by echocardiography), worsened clinical outcome, and impaired bacterial clearance in KO mice. This pathological scenario was paralleled by increased recruitment of pro-inflammatory monocytes and reduced M2-like macrophages within the KO hearts. In peritoneal exudates of KO mice, we quantified increased neutrophil and MHC II+macrophage numbers but decreased monocyte/macrophage and MHC II-macrophage recruitment. hFPR2 upregulation was absent in myeloid cells, and local production of lipoxin A4 was reduced in septic KO mice. Administration of the FPR2 agonist annexin A1 (AnxA1) improved cardiac function in hFPR2 septic mice but had limited beneficial effects in KO mice, in which the FPR2 ligand failed to polarize macrophages toward an MHC II-phenotype. In conclusion, FPR2 deficiency in myeloid cells exacerbates cardiac dysfunction and worsens clinical outcome in polymicrobial sepsis. The improvement of cardiac function and the host immune response by AnxA1 is more effective in hFPR2-competent septic mice.

Published
2022
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42. Investigating Effects of Operational Parameters on the Rate of Electrochemical Cleaning of Chromium Deposits on Strontium-Doped Lanthanum Manganite Cathodes in Solid Oxide Fuel Cells

Author

Sugimoto, Michelle, Zhu, Zhikuan, Gopalan, Srikanth, Basu, Soumendra, and Pal, Uday

Abstract

Chromium poisoning of the cathode remains a significant obstacle to the stable long-term performance of solid oxide fuel cells. This study reports, a quick, in-situ mitigation method, called electrochemical cleaning. By applying a mild anodic bias, the electrochemical deposition reactions of chromium-containing species are reversed. Chromium vapor species are formed, freeing active electrochemical sites in the air electrode. An LSM/YSZ-based cell was exposed to Cr vapors at 800ºC and then subjected to electrochemical cleaning. Cell performance recovery was evidenced by current-voltage and EIS measurements. Chromium removal was verified using SEM and EDS analyses. The cyclability of the electrochemical cleaning was tested by repeated poisoning and cleaning of another cell. Investigation into the effect of cell operating parameters (current density and cell temperature) on the rate of cleaning is discussed.

Published
2021
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44. Annexin A1 and the Resolution of Inflammation: Modulation of Neutrophil Recruitment, Apoptosis, and Clearance

Author

Sugimoto, Michelle Amantéa, Vago, Juliana Priscila, Teixeira, Mauro Martins, and Sousa, Lirlândia Pires

Subjects
endocrine system, Article Subject
Abstract

Neutrophils (also named polymorphonuclear leukocytes or PMN) are essential components of the immune system, rapidly recruited to sites of inflammation, providing the first line of defense against invading pathogens. Since neutrophils can also cause tissue damage, their fine-tuned regulation at the inflammatory site is required for proper resolution of inflammation. Annexin A1 (AnxA1), also known as lipocortin-1, is an endogenous glucocorticoid-regulated protein, which is able to counterregulate the inflammatory events restoring homeostasis. AnxA1 and its mimetic peptides inhibit neutrophil tissue accumulation by reducing leukocyte infiltration and activating neutrophil apoptosis. AnxA1 also promotes monocyte recruitment and clearance of apoptotic leukocytes by macrophages. More recently, some evidence has suggested the ability of AnxA1 to induce macrophage reprogramming toward a resolving phenotype, resulting in reduced production of proinflammatory cytokines and increased release of immunosuppressive and proresolving molecules. The combination of these mechanisms results in an effective resolution of inflammation, pointing to AnxA1 as a promising tool for the development of new therapeutic strategies to treat inflammatory diseases.

Published
2016
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45. Anti-Inflammatory Potential of 1-Nitro-2-Phenylethylene

Author

Sugimoto, Michelle, primary, de Jesus Amazonas da Silva, Márcia, additional, Froede Brito, Larissa, additional, dos Santos Borges, Rosivaldo, additional, Amaral, Flávio, additional, de Araujo Boleti, Ana, additional, Ordoñez, Maritza, additional, Carlos Tavares, Jose, additional, Pires Sousa, Lirlandia, additional, and Lima, Emerson, additional

Published
2017
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47. The resolution of acute inflammation induced by cyclic AMP is dependent on annexin A1

Author

Lima, Kátia M., primary, Vago, Juliana P., additional, Caux, Thaís R., additional, Negreiros-Lima, Graziele Letícia, additional, Sugimoto, Michelle A., additional, Tavares, Luciana P., additional, Arribada, Raquel G., additional, Carmo, Aline Alves F., additional, Galvão, Izabela, additional, Costa, Bruno Rocha C., additional, Soriani, Frederico M., additional, Pinho, Vanessa, additional, Solito, Egle, additional, Perretti, Mauro, additional, Teixeira, Mauro M., additional, and Sousa, Lirlândia P., additional

Published
2017
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48. Knockdown of C-C Chemokine Receptor 5 (CCR5) is Protective Against Cerebral Ischemia and Reperfusion Injury

Author

Victoria, Edna Constanza Gómez, primary, de Brito Toscano, Eliana Cristina, additional, de Sousa Cardoso, Ana Clara, additional, da Silva, Daniele Gonçalves, additional, de Miranda, Aline Silva, additional, da Silva Barcelos, Lucíola, additional, Sugimoto, Michelle Adriane, additional, Sousa, Lirlândia Pires, additional, de Assis Lima, Isabel Vieira, additional, de Oliveira, Antônio Carlos Pinheiro, additional, Brant, Fátima, additional, Machado, Fabiana Simao, additional, Teixeira, Mauro Martins, additional, Teixeira, Antônio Lúcio, additional, and Rachid, Milene Alvarenga, additional

Published
2017
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50. Plasminogen and the Plasminogen Receptor, Plg-RKT, Regulate Macrophage Phenotypic, and Functional Changes.

Author

Vago, Juliana P., Sugimoto, Michelle A., Lima, Kátia M., Negreiros-Lima, Graziele L., Baik, Nagyung, Teixeira, Mauro M., Perretti, Mauro, Parmer, Robert J., Miles, Lindsey A., and Sousa, Lirlândia P.

Subjects
PLASMINOGEN, LEUCOCYTES, PERITONEAL macrophages, PHAGOCYTOSIS, MACROPHAGES, HOMEOSTASIS, PLEURISY
Abstract

Inflammation resolution is an active process that functions to restore tissue homeostasis. Clearance of apoptotic leukocytes by efferocytosis at inflammatory sites plays an important role in inflammation resolution and induces remarkable macrophage phenotypic and functional changes. Here, we investigated the effects of deletion of either plasminogen (Plg) or the Plg receptor, Plg-RKT, on the resolution of inflammation. In a murine model of pleurisy, the numbers of total mononuclear cells recruited to the pleural cavity were significantly decreased in both Plg−/− and Plg-RKT−/− mice, a response associated with decreased levels of the chemokine CCL2 in pleural exudates. Increased percentages of M1-like macrophages were determined in pleural lavages of Plg−/− and Plg-RKT−/− mice without significant changes in M2-like macrophage percentages. In vitro , Plg and plasmin (Pla) increased CD206/Arginase-1 expression and the levels of IL-10/TGF-β (M2 markers) while decreasing IFN/LPS-induced M1 markers in murine bone-marrow-derived macrophages (BMDMs) and human macrophages. Furthermore, IL4-induced M2-like polarization was defective in BMDMs from both Plg−/− and Plg-RKT−/− mice. Mechanistically, Plg and Pla induced transient STAT3 phosphorylation, which was decreased in Plg−/− and Plg-RKT−/− BMDMs after IL-4 or IL-10 stimulation. The extents of expression of CD206 and Annexin A1 (important for clearance of apoptotic cells) were reduced in Plg−/− and Plg-RKT−/− macrophage populations, which exhibited decreased phagocytosis of apoptotic neutrophils (efferocytosis) in vivo and in vitro. Taken together, these results suggest that Plg and its receptor, Plg-RKT, regulate macrophage polarization and efferocytosis, as key contributors to the resolution of inflammation. [ABSTRACT FROM AUTHOR]

Published
2019
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