• 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, Flu Watch Group, Anne M Johnson, and Andrew J McMichael.
• 1 Department of Infectious Disease Informatics, Farr Institute of Health Informatics Research.
• Am. J. Respir. Crit. Care Med. 2015 Jun 15; 191 (12): 1422-31.

RationaleA 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.ObjectivesTo investigate whether naturally preexisting T-cell responses targeting highly conserved internal influenza proteins could provide cross-protective immunity against pandemic and seasonal influenza.MethodsWe 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 ResultsA 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.ConclusionsNaturally 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.

31 keywords...

hide…