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Clin Vaccine Immunol. 2006 Nov;13(11):1223-30. Epub 2006 Sep 20.

Macaque multimeric soluble CD40 ligand and GITR ligand constructs are immunostimulatory molecules in vitro.

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  • 1Department of Medicine, University of California, San Diego, La Jolla, California 92093-0679, USA.

Abstract

CD40 ligand (CD40L) and GITR ligand (glucocorticoid-induced tumor necrosis factor receptor-related protein ligand [GITRL]) are tumor necrosis factor superfamily molecules that can be used as vaccine adjuvants. In a previous human immunodeficiency virus (HIV) DNA vaccine study in mice, we found that plasmids expressing multimeric soluble forms of trimeric CD40L (i.e., many trimers) were stronger activators of CD8(+) T-cell responses than were single-trimer soluble forms or the natural membrane-bound molecule. This report describes similar multimeric soluble molecules that were constructed for studies in macaques. Both two-trimer and four-trimer forms of macaque CD40L were active in B-cell proliferation assays using macaque and human cells. With human cells, four-trimer macaque GITRL costimulated CD4(+) T-cell proliferation and abrogated the immunosuppressive effects of CD4(+) CD25(+) regulatory T cells on a mixed leukocyte reaction. These molecular adjuvants provide new tools for vaccine development in the simian immunodeficiency virus system and other macaque models.

PMID:
16988005
[PubMed - indexed for MEDLINE]
PMCID:
PMC1656546
Free PMC Article
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