GLA-SE, a synthetic toll-like receptor 4 agonist, enhances T-cell responses to influenza vaccine in older adults

Hayedeh Behzad, Anke L.W. Huckriede, Laura Haynes, Beth Gentleman, Krysta Coyle, Jan C. Wilschut, Tobias R. Kollmann, Steven G. Reed, Janet E. McElhaney*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

Background. The decline in influenza vaccine efficacy in older adults is associated with a limited ability of current split-virus vaccines (SVVs) to stimulate cytotoxic T lymphocyte (CTL) responses required for clinical protection against influenza. Methods. The Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE) was combined with SVV to stimulate peripheral blood mononuclear cells (PBMCs) in vitro to determine the cytokine response in dendritic cell subsets. Stimulated PBMCs were then challenged with live influenza virus to mimic the response to natural infection following vaccination, using previously identified T-cell correlates of protection. Results. GLA-SE significantly increased the proportion of myeloid dendritic cells that produced tumor necrosis factor α, interleukin 6, and interleukin 12. When combined with SVV to stimulate PBMCs in vitro, this effect of GLA-SE was shown to regulate a T-helper 1 cell response upon challenge with live influenza virus; interleukin 10 production was suppressed, thus significantly increasing the interferon γ to interleukin 10 ratio and the cytolytic (granzyme B) response to influenza virus challenge, both of which have been shown to correlate with protection against influenza in older adults. Conclusions. Our findings suggest that a novel adjuvant, GLA-SE, combined with standard SVV has the potential to significantly improve vaccine-mediated protection against influenza in older adults.

Original languageEnglish (US)
Pages (from-to)466-473
Number of pages8
JournalJournal of Infectious Diseases
Volume205
Issue number3
DOIs
StatePublished - Feb 1 2012
Externally publishedYes

Bibliographical note

Funding Information:
Financial support. This work was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (U01 AI074449). The Network of Centres of Excellence in Vaccines and Im-munotherapeutics in Canada supported the development of the GrzB assay, and the Canadian Institutes of Health Research supported the validation of the GrzB activity and cytokine assays, according to International Conference on Harmonisation guidelines. The study was conducted through the VITALiTY Research Unit, Vancouver Coastal Health Research Institute (Vancouver, BC, Canada).

ASJC Scopus subject areas

  • General Medicine

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