Hayward, AC; Wang, L; Goonetilleke, N; Fragaszy, EB; Bermingham, A; Copas, A; Dukes, O; ... Flu Watch Group; + view all Hayward, AC; 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; - view fewer (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.

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