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 journalArticle

100 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 (US)
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
StatePublished - Mar 3 2009

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Natural Killer T-Cells
Influenza A virus
Cytotoxic T-Lymphocytes
Orthomyxoviridae
Immunity
Vaccination
Vaccines
Indoleamine-Pyrrole 2,3,-Dioxygenase
Galactosylceramides
Influenza Vaccines
Glycolipids
Pandemics
Cellular Immunity
Epitopes
Up-Regulation
T-Lymphocytes
Population
Genes

Keywords

  • Adjuvant
  • T cell memory
  • Vaccine
  • Viral immunity

ASJC Scopus subject areas

  • General

Cite this

Combined NKT cell activation and influenza virus vaccination boosts memory CTL generation and protective immunity. / Guillonneau, Carole; Mintern, Justine D.; Hubert, François Xavier; Hurt, Aeron C.; Besra, Gurdyal S.; Porcelli, Steven A.; Barr, Ian G.; Doherty, Peter C.; Godfrey, Dale I.; Turner, Stephen J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 9, 03.03.2009, p. 3330-3335.

Research output: Contribution to journalArticle

Guillonneau, Carole ; Mintern, Justine D. ; Hubert, François Xavier ; Hurt, Aeron C. ; Besra, Gurdyal S. ; Porcelli, Steven A. ; Barr, Ian G. ; Doherty, Peter C. ; Godfrey, Dale I. ; Turner, Stephen J. / Combined NKT cell activation and influenza virus vaccination boosts memory CTL generation and protective immunity. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 9. pp. 3330-3335.
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