Sridhar, S., Begom, S., Bermingham, A., Hoschler, K., Adamson, W., Carman, W., Bean, T., Barclay, W., Deeks, J.J. and Lalvani, A. (2013) Cellular immune correlates of protection against symptomatic pandemic influenza. Nature Medicine, 19(10), pp. 1305-1312. (doi: 10.1038/nm.3350)
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Abstract
The role of T cells in mediating heterosubtypic protection against natural influenza illness in humans is uncertain. The 2009 H1N1 pandemic (pH1N1) provided a unique natural experiment to determine whether crossreactive cellular immunity limits symptomatic illness in antibody-naive individuals. We followed 342 healthy adults through the UK pandemic waves and correlated the responses of pre-existing T cells to the pH1N1 virus and conserved core protein epitopes with clinical outcomes after incident pH1N1 infection. Higher frequencies of pre-existing T cells to conserved CD8 epitopes were found in individuals who developed less severe illness, with total symptom score having the strongest inverse correlation with the frequency of interferon-γ (IFN-γ)+ interleukin-2 (IL-2)− CD8+ T cells (r = −0.6, P = 0.004). Within this functional CD8+IFN-γ+IL-2− population, cells with the CD45RA+ chemokine (C-C) receptor 7 (CCR7)− phenotype inversely correlated with symptom score and had lung-homing and cytotoxic potential. In the absence of crossreactive neutralizing antibodies, CD8+ T cells specific to conserved viral epitopes correlated with crossprotection against symptomatic influenza. This protective immune correlate could guide universal influenza vaccine development.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Carman, Professor William and Adamson, Dr Walt |
| Authors: | Sridhar, S., Begom, S., Bermingham, A., Hoschler, K., Adamson, W., Carman, W., Bean, T., Barclay, W., Deeks, J.J., and Lalvani, A. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Nature Medicine |
| Publisher: | Nature Publishing Group |
| ISSN: | 1078-8956 |
| ISSN (Online): | 1546-170X |
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