Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2

Autor: 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.
Přispěvatelé: 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), Multiple Sclerosis Society
Jazyk: angličtina
Rok vydání: 2021
Předmět:
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
ISSN: 0028-0836
1476-4687
Popis: 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.
Databáze: OpenAIRE
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