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

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

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.

Citation

Hayward, A. C., Wang, L., Goonetilleke, N., Fragaszy, E. B., Bermingham, A., Copas, A., Dukes, O., Millett, E. R., Nazareth, I., Nguyen-Van-Tam, J. S., Watson, J. M., Zambon, M., Johnson, A. M., & McMichael, A. 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), 1422-1431. https://doi.org/10.1164/rccm.201411-1988oc

• Journal Article Type: Article
• Acceptance Date: Mar 30, 2015
• Online Publication Date: Jun 15, 2015
• Publication Date: Jun 15, 2015
• Deposit Date: Apr 5, 2017
• Publicly Available Date: Apr 5, 2017
• Journal: American Journal of Respiratory and Critical Care Medicine
• Print ISSN: 1073-449X
• Electronic ISSN: 1535-4970
• Publisher: American Thoracic Society
• Peer Reviewed: Peer Reviewed
• Volume: 191
• Issue: 12
• Pages: 1422-1431
• DOI: https://doi.org/10.1164/rccm.201411-1988oc
• Keywords: cellular immunity; T lymphocytes; cohort studies
• Public URL: https://nottingham-repository.worktribe.com/output/754328
• Publisher URL: http://www.atsjournals.org/doi/10.1164/rccm.201411-1988OC
• Related Public URLs: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476562/
• Contract Date: Apr 5, 2017