Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 9, Pages 3330-3335Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0813309106
Keywords
T cell memory; viral immunity; vaccine; adjuvant
Categories
Funding
- National Health and Medical Research Council (NHMRC) [499455]
- Sixth Framework Programme of the European Union, Marie Curie [040840]
- Fondation pour la Recherche Medicale
- NHMRC Project [454595]
- National Institutes of Health [AI70251]
- NHMRC Principal Research Fellowship
- Pfizer Senior Research Fellowship
- CJ Martin Fellowship
- Marie Curie Fellowship [040998]
- Medical Research Council [G9901077, G0500590]
- The Wellcome Trust [081569/2/06/2]
- Australian Government Department of Health and Aging
- Medical Research Council [G9901077, G0500590, G0400421] Funding Source: researchfish
- MRC [G9901077, G0400421, G0500590] Funding Source: UKRI
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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.
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