Hayward, AC;
Wang, L;
Goonetilleke, N;
Fragaszy, EB;
Bermingham, A;
Copas, A;
Dukes, O;
... Flu Watch Group; + view all
(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.
10.1164/rccm.201411-1988OC.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Natural T Cell Mediated Protection Against Seasonal and Pandemic Influenza: Results of the Flu Watch Cohort Study |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1164/rccm.201411-1988OC |
| Publisher version: | http://dx.doi.org/10.1164/rccm.201411-1988OC |
| Language: | English |
| Additional information: | Originally Published in: Hayward, AC; Wang, L; Goonetilleke, N; Fragaszy, EB; Bermingham, A; Copas, A; Dukes, O; (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. DOI: 10.1164/rccm.201411-1988OC Copyright © 2015 by the American Thoracic Society The final publication is available at http://dx.doi.org/10.1164/rccm.201411-1988OC. |
| Keywords: | Cellular Immunity, Cohort Studies, T-Lymphocytes |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health > Infection and Population Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Primary Care and Population Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1466815 |
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