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

Carole Guillonneau, Justine D. Mintern, François Xavier Hubert, Aeron C. Hurt, Gurdyal S Besra, Steven A Porcelli, Ian G. Barr, Peter C Doherty, Dale I. Godfrey, Stephen J. Turner

Research output: Contribution to journalArticleResearchpeer-review

106 Citations (Scopus)

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 α-galactosylceramide (α-GalCer). We show here that giving α-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 α-GalCer-induced upregulation of prosurvival genes, such as bcl-2, and points to the potential of α-GalCer as an adjuvant for promoting optimal, vaccine-induced CD8+ T cell memory.

Original languageEnglish
Pages (from-to)3330-3335
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number9
DOIs
Publication statusPublished - 3 Mar 2009
Externally publishedYes

Keywords

  • Adjuvant
  • T cell memory
  • Vaccine
  • Viral immunity

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