Combined NKT cell activation and influenza virus vaccination boosts memory CTL generation and protective immunity

Research output: Contribution to journalArticle

Authors

  • C Guillonneau
  • JD Mintern
  • FX Hubert
  • AC Hurt
  • S Porcelli
  • IG Barr
  • PC Doherty
  • DI Godfrey
  • SJ Turner

Colleges, School and Institutes

Abstract

Current influenza A virus vaccines do not generate significant immunity against serologically distinct influenza A virus subtypes and would thus be ineffective in the face of a pandemic caused by a novel variant emerging from, say, a wildlife reservoir. One possible solution would be to modify these vaccines so that they prime cross-reactive CD8(+) cytotoxic T lymphocytes (CTL) cell-mediated immunity directed at conserved viral epitopes. A further strategy is to use novel adjuvants, such as the immunomodulatory glycolipid alpha-galactosylceramide (alpha-GalCer). We show here that giving alpha-GalCer with an inactivated influenza A virus has the paradoxical effect of diminishing acute CTL immunity via natural killer T (NKT) cell-dependent expression of indoleamine 2,3-dioxygenase (IDO), an important mediator of immune suppression, while at the same time promoting the survival of long-lived memory CTL populations capable of boosting protection against heterologous influenza A virus challenge. This enhancement of memory was likely due to the alpha-GalCer-induced upregulation of prosurvival genes, such as bcl-2, and points to the potential of alpha-GalCer as an adjuvant for promoting optimal, vaccine-induced CD8(+) T cell memory.

Details

Original languageEnglish
Pages (from-to)3330-3335
Number of pages6
JournalNational Academy of Sciences. Proceedings
Volume106
Issue number9
Publication statusPublished - 1 Mar 2009

Keywords

  • adjuvant, T cell memory, viral immunity, vaccine