Journal of Endotoxin Research

 

Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Register here to gain access to SAGE's 500+ Journals Online

Sign In to gain access to subscriptions and/or personal tools.
This Article
Right arrow Full Text (PDF)
Right arrow References
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Steeghs, L.
Right arrow Articles by van der Ley, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Steeghs, L.
Right arrow Articles by van der Ley, P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Journal of Endotoxin Research, Vol. 10, No. 2, 113-119 (2004)
DOI: 10.1177/09680519040100020701

Teasing apart structural determinants of `toxicity' and `adjuvanticity': implications for meningococcal vaccine development

Liana Steeghs

Laboratory of Immunotherapy, Department of Immunology, University Medical Centre Utrecht, The Netherlands, steeghs{at}lab.azu.nl

Jan Tommassen

Department of Molecular Microbiology and Institute of Biomembranes, Utrecht University, The Netherlands

Jeanette H.W. Leusen

Laboratory of Immunotherapy, Department of Immunology, University Medical Centre Utrecht, The Netherlands

Jan G.J. van de Winkel

Laboratory of Immunotherapy, Department of Immunology, University Medical Centre Utrecht, The Netherlands

Peter van der Ley

Department of Research and Development, Netherlands Vaccine Institute, The Netherlands

The use of lipopolysaccharide (LPS) as an adjuvant is limited by its high endotoxic activity. In particular, the fatty-acyl pattern of the lipid A part of LPS has been demonstrated to determine its biological activity. By genetic modification of the lipid A biosynthesis pathway in Neisseria meningitidis, a panel of recombinant strains with specific alterations in the lipid A acylation pattern, as well as a strain completely lacking LPS were isolated. Whereas all variations in the fatty-acyl pattern resulted in reduced endotoxic activity, as measured by TNF-{alpha} induction in the human macrophage cell line MM6, the adjuvant activity of the modified LPS was, in most cases, barely affected. The in vivo adjuvant properties of N. meningitidis wild-type and mutant LPS was found to correlate with induction of co-stimulatory molecules, in particular CD80 and CD40, and with IL-12 production by LPS-stimulated bone marrow-derived BALB/c dendritic cells in vitro. Our results suggest that the ability of LPS to stimulate pro-inflammatory cytokine induction is not necessarily linked to its adjuvant activity. The availability of this novel set of lipid A variants with improved pharmacological properties will be of great importance for the improvement of future outer membrane vesicle vaccines against N. meningitidis.

Key Words: Neisseria meningitidis • lipid A mutants • endotoxicity • adjuvanticity • outer membrane vesicle vaccines


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?