HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ebensen, T. Articles by Guzmán, C. A. Search for Related Content PubMed PubMed Citation Articles by Ebensen, T. Articles by Guzmán, C. A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Immunization

A Pegylated Derivative of -Galactosylceramide Exhibits Improved Biological Properties

Department of Vaccinology, Helmholtz Centre for Infection Research, Braunschweig, Germany

The glycolipid -galactosylceramide (GalCer) has immunomodulatory properties, which have been exploited to combat cancer, chronic inflammatory diseases, and infections. However, its poor solubility makes GalCer a suboptimal compound for in vivo applications. In this study, a pegylated derivative of GalCer is characterized, which exhibits improved physical and biological properties. The new compound, GalCerMPEG, is water-soluble and retains the specificity for the CD1d receptor of GalCer. The in vitro stimulatory properties on immune cells (e.g., dendritic cells and splenocytes) are maintained intact, even when tested at a 33-fold lower concentration of the active moiety than GalCer. NK cells isolated from mice treated with GalCerMPEG also had stronger cytotoxic activity on YAC-1 cells than those obtained from animals receiving either GalCer or CpG. Intranasal immunization studies performed in mice showed that GalCerMPEG exerts stronger adjuvant activities than the parental compound GalCer when tested at 0.35 vs 11.7 nM/dose. Coadministration of -galactosidase with GalCerMPEG resulted not only in high titers of Ag-specific Abs in serum (i.e., 1:512,000), but also in the stimulation of stronger Th2 and secretory IgA responses, both at local and remote mucosal effector sites (i.e., nose, lung, and vagina). The new synthetic derivative GalCerMPEG represents a promising tool for the development of immune interventions against infectious and noninfectious diseases.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ T.E. and C.L. equally contributed to the work.

² Address correspondence and reprint requests to Dr. Carlos A. Guzmán, Department of Vaccinology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany. E-mail address: cag{at}helmholtz-hzi.de

³ Abbreviations used in this paper: GalCer, -galactosylceramide; PEG, polyethylene glycol; DC, dendritic cell; i.n., intranasal; -Gal, -galactosidase; GalCerMPEG, pegylated derivative of GalCer; ANS, I-anilino-8-naphthalenesulfonate; BAL, bronchial alveolar lavage; NL, nasal lavage; MFI, mean fluorescence intensity; sIgA, secretory IgA.