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Am J Respir Crit Care Med. 2015 Jun 15;191(12):1422-31. doi: 10.1164/rccm.201411-1988OC.

Natural T Cell-mediated Protection against Seasonal and Pandemic Influenza. Results of the Flu Watch Cohort Study.

Author information

1
1 Department of Infectious Disease Informatics, Farr Institute of Health Informatics Research.
2
2 Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
3
3 Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
4
4 Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
5
5 Respiratory Virus Unit, Centre for Infections, Public Health England, Colindale, United Kingdom.
6
6 Research Department of Infection and Population Health, and.
7
7 Department of Primary Care and Population Health, University College London, London, United Kingdom.
8
8 Health Protection and Influenza Research Group, Division of Epidemiology and Public Health, University of Nottingham, Nottingham, United Kingdom; and.
9
9 Department of Health, London, United Kingdom.

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.

KEYWORDS:

T lymphocytes; cellular immunity; cohort studies

PMID:
25844934
PMCID:
PMC4476562
DOI:
10.1164/rccm.201411-1988OC
[Indexed for MEDLINE]
Free PMC Article

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