Cellular immune correlates of protection against symptomatic pandemic influenza

Saranya Sridhar, Shaima Begom, Alison Bermingham, Katja Hoschler, Walt Adamson, William Carman, Thomas Bean, Wendy Barclay, Jonathan J Deeks, Ajit Lalvani

    Research output: Contribution to journalArticlepeer-review

    471 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)1305-12
    Number of pages8
    JournalNature Medicine
    Volume19
    Issue number10
    DOIs
    Publication statusPublished - Oct 2013

    Keywords

    • Adult
    • CD8-Positive T-Lymphocytes
    • Cohort Studies
    • Cross Reactions
    • Great Britain
    • Humans
    • Immunity, Cellular
    • Immunologic Memory
    • Immunophenotyping
    • Influenza A Virus, H1N1 Subtype
    • Influenza, Human
    • Severity of Illness Index
    • Virus Shedding

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