Cellular immune correlates of protection against symptomatic pandemic influenza.
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.
Respiratory Infections Section, National Heart and Lung Institute, Imperial College London, London, UK.
Saranya
S
Sridhar
Shaima
S
Begom
Alison
A
Bermingham
Katja
K
Hoschler
Walt
W
Adamson
William
W
Carman
Thomas
T
Bean
Wendy
W
Barclay
Jonathan J
JJ
Deeks
Ajit
A
Lalvani
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D003429:Cross Reactions; D006801:Humans; D007111:Immunity, Cellular; D007156:Immunologic Memory; D016130:Immunophenotyping; D053118:Influenza A Virus, H1N1 Subtype / Q000302:isolation & purification; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D012720:Severity of Illness Index; D006113:United Kingdom / Q000453:epidemiology; D017201:Virus Shedding