Natural T cell–mediated protection against seasonal and pandemic Influenza: results of the Flu Watch cohort study

Hayward, Andrew C. and Wang, Lili and Goonetilleke, Nilu and Fragaszy, Ellen B. and Bermingham, Alison and Copas, Andrew and Dukes, Oliver and Millett, Elizabeth R.C. and Nazareth, Irwin and Nguyen-Van-Tam, Jonathan S. and Watson, John M. and Zambon, Maria and 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

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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.

Item Type: Article
Keywords: cellular immunity; T lymphocytes; cohort studies
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Epidemiology and Public Health
Identification Number: 10.1164/rccm.201411-1988OC
Related URLs:
Depositing User: Claringburn, Tara
Date Deposited: 05 Apr 2017 10:48
Last Modified: 19 Nov 2017 18:40
URI: http://eprints.nottingham.ac.uk/id/eprint/41751

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