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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.

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Authors

Andrew C. Hayward

Lili Wang

Nilu Goonetilleke

Ellen B. Fragaszy

Alison Bermingham

Andrew Copas

Oliver Dukes

Elizabeth R.C. Millett

Irwin Nazareth

Jonathan S. Nguyen-Van-Tam

John M. Watson

Maria Zambon

Anne M. Johnson

Andrew J. McMichael



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.

Citation

Hayward, A. C., Wang, L., Goonetilleke, N., Fragaszy, E. B., Bermingham, A., Copas, A., Dukes, O., Millett, E. R., Nazareth, I., Nguyen-Van-Tam, J. S., Watson, J. M., Zambon, M., Johnson, A. M., & McMichael, A. 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), 1422-1431. https://doi.org/10.1164/rccm.201411-1988oc

Journal Article Type Article
Acceptance Date Mar 30, 2015
Online Publication Date Jun 15, 2015
Publication Date Jun 15, 2015
Deposit Date Apr 5, 2017
Publicly Available Date Apr 5, 2017
Journal American Journal of Respiratory and Critical Care Medicine
Print ISSN 1073-449X
Electronic ISSN 1535-4970
Publisher American Thoracic Society
Peer Reviewed Peer Reviewed
Volume 191
Issue 12
Pages 1422-1431
DOI https://doi.org/10.1164/rccm.201411-1988oc
Keywords cellular immunity; T lymphocytes; cohort studies
Public URL https://nottingham-repository.worktribe.com/output/754328
Publisher URL http://www.atsjournals.org/doi/10.1164/rccm.201411-1988OC
Related Public URLs http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476562/
Contract Date Apr 5, 2017

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