Natural T cell–mediated protection against seasonal and pandemic Influenza: results of the Flu Watch cohort study
Rationale: A high proportion of influenza infections are asymptomatic. Animal and human challenge studies and observational studies suggest T cells protect against disease among those infected, but the impact of T-cell immunity at the population level is unknown. Objectives: To investigate wheth...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
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American Thoracic Society
2015
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| Online Access: | https://eprints.nottingham.ac.uk/41751/ |
| _version_ | 1848796345653002240 |
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| author | Hayward, Andrew C. Wang, Lili Goonetilleke, Nilu Fragaszy, Ellen B. Bermingham, Alison Copas, Andrew Dukes, Oliver Millett, Elizabeth R.C. Nazareth, Irwin Nguyen-Van-Tam, Jonathan S. Watson, John M. Zambon, Maria Johnson, Anne M. McMichael, Andrew J. |
| author_facet | Hayward, Andrew C. Wang, Lili Goonetilleke, Nilu Fragaszy, Ellen B. Bermingham, Alison Copas, Andrew Dukes, Oliver Millett, Elizabeth R.C. Nazareth, Irwin Nguyen-Van-Tam, Jonathan S. Watson, John M. Zambon, Maria Johnson, Anne M. McMichael, Andrew J. |
| author_sort | Hayward, Andrew C. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Rationale: A high proportion of influenza infections are asymptomatic. Animal and human challenge studies and observational studies suggest T cells protect against disease among those infected, but the impact of T-cell immunity at the population level is unknown.
Objectives: To investigate whether naturally preexisting T-cell responses targeting highly conserved internal influenza proteins could provide cross-protective immunity against pandemic and seasonal influenza.
Methods: We quantified influenza A(H3N2) virus–specific T cells in a population cohort during seasonal and pandemic periods between 2006 and 2010. Follow-up included paired serology, symptom reporting, and polymerase chain reaction (PCR) investigation of symptomatic cases.
Measurements and Main Results: A total of 1,414 unvaccinated individuals had baseline T-cell measurements (1,703 participant observation sets). T-cell responses to A(H3N2) virus nucleoprotein (NP) dominated and strongly cross-reacted with A(H1N1)pdm09 NP (P < 0.001) in participants lacking antibody to A(H1N1)pdm09. Comparison of paired preseason and post-season sera (1,431 sets) showed 205 (14%) had evidence of infection based on fourfold influenza antibody titer rises. The presence of NP-specific T cells before exposure to virus correlated with less symptomatic, PCR-positive influenza A (overall adjusted odds ratio, 0.27; 95% confidence interval, 0.11–0.68; P = 0.005, during pandemic [P = 0.047] and seasonal [P = 0.049] periods). Protection was independent of baseline antibodies. Influenza-specific T-cell responses were detected in 43%, indicating a substantial population impact.
Conclusions: Naturally occurring cross-protective T-cell immunity protects against symptomatic PCR-confirmed disease in those with evidence of infection and helps to explain why many infections do not cause symptoms. Vaccines stimulating T cells may provide important cross-protective immunity. |
| first_indexed | 2025-11-14T19:46:31Z |
| format | Article |
| id | nottingham-41751 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:46:31Z |
| publishDate | 2015 |
| publisher | American Thoracic Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-417512024-08-15T15:17:09Z https://eprints.nottingham.ac.uk/41751/ Natural T cell–mediated protection against seasonal and pandemic Influenza: results of the Flu Watch cohort study Hayward, Andrew C. Wang, Lili Goonetilleke, Nilu Fragaszy, Ellen B. Bermingham, Alison Copas, Andrew Dukes, Oliver Millett, Elizabeth R.C. Nazareth, Irwin Nguyen-Van-Tam, Jonathan S. Watson, John M. Zambon, Maria Johnson, Anne M. McMichael, Andrew J. Rationale: A high proportion of influenza infections are asymptomatic. Animal and human challenge studies and observational studies suggest T cells protect against disease among those infected, but the impact of T-cell immunity at the population level is unknown. Objectives: To investigate whether naturally preexisting T-cell responses targeting highly conserved internal influenza proteins could provide cross-protective immunity against pandemic and seasonal influenza. Methods: We quantified influenza A(H3N2) virus–specific T cells in a population cohort during seasonal and pandemic periods between 2006 and 2010. Follow-up included paired serology, symptom reporting, and polymerase chain reaction (PCR) investigation of symptomatic cases. Measurements and Main Results: A total of 1,414 unvaccinated individuals had baseline T-cell measurements (1,703 participant observation sets). T-cell responses to A(H3N2) virus nucleoprotein (NP) dominated and strongly cross-reacted with A(H1N1)pdm09 NP (P < 0.001) in participants lacking antibody to A(H1N1)pdm09. Comparison of paired preseason and post-season sera (1,431 sets) showed 205 (14%) had evidence of infection based on fourfold influenza antibody titer rises. The presence of NP-specific T cells before exposure to virus correlated with less symptomatic, PCR-positive influenza A (overall adjusted odds ratio, 0.27; 95% confidence interval, 0.11–0.68; P = 0.005, during pandemic [P = 0.047] and seasonal [P = 0.049] periods). Protection was independent of baseline antibodies. Influenza-specific T-cell responses were detected in 43%, indicating a substantial population impact. Conclusions: Naturally occurring cross-protective T-cell immunity protects against symptomatic PCR-confirmed disease in those with evidence of infection and helps to explain why many infections do not cause symptoms. Vaccines stimulating T cells may provide important cross-protective immunity. American Thoracic Society 2015-06-15 Article PeerReviewed Hayward, Andrew C., Wang, Lili, Goonetilleke, Nilu, Fragaszy, Ellen B., Bermingham, Alison, Copas, Andrew, Dukes, Oliver, Millett, Elizabeth R.C., Nazareth, Irwin, Nguyen-Van-Tam, Jonathan S., Watson, John M., Zambon, Maria, Johnson, Anne M. and McMichael, Andrew J. (2015) Natural T cell–mediated protection against seasonal and pandemic Influenza: results of the Flu Watch cohort study. American Journal of Respiratory and Critical Care Medicine, 191 (12). pp. 1422-1431. ISSN 1535-4970 cellular immunity; T lymphocytes; cohort studies http://www.atsjournals.org/doi/10.1164/rccm.201411-1988OC doi:10.1164/rccm.201411-1988OC doi:10.1164/rccm.201411-1988OC |
| spellingShingle | cellular immunity; T lymphocytes; cohort studies Hayward, Andrew C. Wang, Lili Goonetilleke, Nilu Fragaszy, Ellen B. Bermingham, Alison Copas, Andrew Dukes, Oliver Millett, Elizabeth R.C. Nazareth, Irwin Nguyen-Van-Tam, Jonathan S. Watson, John M. Zambon, Maria Johnson, Anne M. McMichael, Andrew J. Natural T cell–mediated protection against seasonal and pandemic Influenza: results of the Flu Watch cohort study |
| title | Natural T cell–mediated protection against seasonal and pandemic Influenza: results of the Flu Watch cohort study |
| title_full | Natural T cell–mediated protection against seasonal and pandemic Influenza: results of the Flu Watch cohort study |
| title_fullStr | Natural T cell–mediated protection against seasonal and pandemic Influenza: results of the Flu Watch cohort study |
| title_full_unstemmed | Natural T cell–mediated protection against seasonal and pandemic Influenza: results of the Flu Watch cohort study |
| title_short | Natural T cell–mediated protection against seasonal and pandemic Influenza: results of the Flu Watch cohort study |
| title_sort | natural t cell–mediated protection against seasonal and pandemic influenza: results of the flu watch cohort study |
| topic | cellular immunity; T lymphocytes; cohort studies |
| url | https://eprints.nottingham.ac.uk/41751/ https://eprints.nottingham.ac.uk/41751/ https://eprints.nottingham.ac.uk/41751/ |