Abstracts (complete list) - Wissenschaft Online

Peggy Riese, Thomas Ebensen, Claudia Link, Kai Schulze, Michael Morr, Carlos Guzmán
A pegylated derivative of alpha galactosylceramide exhibits
improved immune stimulatory activities
The glycolipid alpha galactosylceramide (alpha GalCer) has immune modulatory
properties, leading to activation of various cell subsets of the innate and adaptive
immune system. However, its poor solubility makes alpha GalCer a suboptimal
compound for in vivo applications. A well-known method to improve the solubility of
chemical compounds in aqueous solutions is the conjugation with polyethylene glycol. A
pegylated derivative of alpha GalCer, called alpha GalCerMPEG, is characterized, which
exhibits improved physiological and biological activities. The new compound is watersoluble
and retains the specificity for the CD1d receptor of alpha GalCer. In vitro studies
showed the same stimulating activities on different subsets of immune cells (dendritic
cells, natural killer cells), even when tested at 33-fold lower concentrations. Natural
killer cells isolated from mice treated with alpha GalCerMPEG have also stronger activity
on Yac-1 cells than those obtained from animals receiving either alpha GalCer or CpG.
Intranasal immunisation studies performed in mice showed, that alpha GalCerMPEG
exerts stronger adjuvant activities than the parental compound alpha GalCer. Coadministration
of beta-galactosidase with alpha GalCerMPEG resulted not only in high
titers of antigen-specific antibodies in serum, but also in the stimulation of stronger Th2
and sIgA responses, both at local and remote mucosal effector sites (i.e., nose, lung,
vagina). The new synthetic derivative alpha GalCerMPEG represents a promising tool for
the development of immune interventions against infectious and non-infectious diseases.