Lipid-containing mimetics of natural triggers of innate immunity as CTL-inducing influenza vaccines

Yuk Lau, Georgia Deliyannis, Weiguang Zeng, Ashley Mansell, David Jackson, Lorena Brown

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54 Citations (Scopus)

Abstract

Anti-viral CD8(+) T cell responses can be induced using synthetic lipopeptides and a range of different lipid moieties have been examined in a variety of model systems and in man for this purpose. Nevertheless, only limited data exist on comparative efficacy of different lipopeptides in a single model of protection so that the optimal composition for vaccination purposes remains unknown. In this study, we examined different lipid structures from bacterial or non-bacterial sources coupled to peptides representing influenza viral epitopes recognized by CD8(+) and CD4(+) T cells. These were assessed in the context of intra-nasal (i.n.) immunization in the absence of added adjuvant. The strongest immunogens were those containing bacterially derived lipids that induced dendritic cell (DC) maturation via Toll-like receptor 2 (TLR2) binding. The number of DCs induced to mature in vitro was directly associated with the strength of the CD8(+) T cell-mediated viral clearing responses in primed mice. Mice immunized with the TLR2-binding lipopeptides showed greatly enhanced numbers of specific IFN-gamma-secreting CD8(+) T cells at the site of infection after i.n. exposure to virus, which resulted in enhanced protection of the pneumonic lung. Importantly, lipopeptide-pulsed DCs were able to induce the appropriate T cells, indicating that the self-adjuvanting effects could occur in the absence of free lipopeptide interacting with additional TLR2-bearing cells in vivo. This study defines a hierarchy of lipopeptide constructs that can program DC to prime memory CD8(+) T cells that on recall function to clear influenza virus from the infected lung.
Original languageEnglish
Pages (from-to)1801 - 1813
Number of pages13
JournalInternational Immunology
Volume18
Issue number12
DOIs
Publication statusPublished - 2006

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