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

Guillonneau, C; Mintern, JD; Hubert, FX; Hurt, AC; Besra, GS; Porcelli, S; Barr, IG; Doherty, PC; Godfrey, DI; Turner, SJ

Author(s): Guillonneau, C; Mintern, JD; Hubert, FX; Hurt, AC; Besra, GS; Porcelli, S; Barr, IG; Doherty, PC; Godfrey, DI; Turner, SJ;
Details: Publication Year 2009-03-03,Volume 106,Issue #9,Page 3330-3335
Journal Title: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Publication Type: Journal Article
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.
Publisher: NATL ACAD SCIENCES
Keywords: CD8(+) T-CELLS; ALPHA-GALACTOSYLCERAMIDE; DENDRITIC CELLS; IN-VIVO; INDOLEAMINE 2,3-DIOXYGENASE; ANTIGEN PRESENTATION; INFECTION; RESPONSES; VACCINES; COSTIMULATION
Publisher's Version: https://doi.org/10.1073/pnas.0813309106
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2009-03-03 12:00:00