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Natural T Cell Mediated Protection Against Seasonal and Pandemic Influenza: Results of the Flu Watch Cohort Study

tetano

Editor, Senior Moderator
Am J Respir Crit Care Med. 2015 Apr 6. [Epub ahead of print]
[h=1]Natural T Cell Mediated Protection Against Seasonal and Pandemic Influenza: Results of the Flu Watch Cohort Study.[/h] Hayward AC[SUP]1[/SUP], Wang L, Goonetilleke N, Fragaszy EB, Bermingham A, Copas A, Dukes O, Millett ER, Nazareth I, Nguyen-Van-Tam JS, Watson JM, Zambon M, Johnson AM, McMichael AJ; Flu Watch Group.
[h=3]Author information[/h]

[h=3]Abstract[/h] [h=4]RATIONALE:[/h] 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.
[h=4]OBJECTIVES:[/h] To investigate whether naturally pre-existing T cell responses targeting highly conserved internal influenza proteins could provide cross-protective immunity against pandemic and seasonal influenza.
[h=4]METHODS:[/h] We quantified influenza A(H3N2) virus specific T cells in a population cohort during seasonal and pandemic periods between 2006-2010. Follow-up included paired serology, symptom reporting and PCR investigation of symptomatic cases.
[h=4]MEASUREMENTS AND MAIN RESULTS:[/h] 1414 unvaccinated individuals had baseline T cell measurements: (1703 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 pre- and post-season sera (1431 sets) showed 205 (14%) had evidence of infection based on four-fold influenza antibody titre 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 periods (p=0.049)). Protection was independent of baseline antibodies. Influenza specific T cell responses were detected in 43% indicating a substantial population impact.
[h=4]CONCLUSIONS:[/h] 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.


[h=4]KEYWORDS:[/h] Cellular Immunity; Cohort Studies; T-Lymphocytes

PMID: 25844934 [PubMed - as supplied by publisher]
 
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