Cellular immune correlates of protection against symptomatic pandemic influenza

Research output: Contribution to journalArticle

Authors

  • Saranya Sridhar
  • Shaima Begom
  • Alison Bermingham
  • Katja Hoschler
  • Walt Adamson
  • William Carman
  • Thomas Bean
  • Wendy Barclay
  • Ajit Lalvani

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.

Details

Original languageEnglish
Pages (from-to)1305-12
Number of pages8
JournalNature Medicine
Volume19
Issue number10
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