Amine-reactive OVA multimers for auto-vaccination against cytokines and other mediators: perspectives illustrated for GCP-2 in L. major infection

Journal of Leukocyte Biology

Mélanie Charmoy⁴  Rachel R. Caspi–²  Fabienne Tacchini-Cottier⁴  Dan Su⁸  Ghislain Opdenakker# and¹  Sofie Struyf⁶  Jo Van Damme⁶  Jacques Van Snick⁵  Catherine Uyttenhove⁷  Jesse M. Damsker–²  Stanislas Goriely³  Reece G. Marillier⁵ 

[1] #Immunobiology, Rega Institute for Medical Research, K.U. Leuven, Leuven, Belgium Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium;;–Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA; and #Immunobiology, Rega Institute for Medical Research, K.U. Leuven, Leuven, Belgium Cellular Genetics Unit and #Immunobiology, Rega Institute for Medical Research, K.U. Leuven, Leuven, Belgium Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium;;WHO Immunology Research and Training Center, Department of Biochemistry, University of Lausanne, Epalinges, Switzerland; #Immunobiology, Rega Institute for Medical Research, K.U. Leuven, Leuven, Belgium;Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium; Experimental Medicine Unit, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; #Immunobiology, Rega Institute for Medical Research, K.U. Leuven, Leuven, BelgiumLaboratories of Molecular Immunology and #Immunobiology, Rega Institute for Medical Research, K.U. Leuven, Leuven, Belgium Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium;;Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium;  Cellular Genetics Unit and #Immunobiology, Rega Institute for Medical Research, K.U. Leuven, Leuven, Belgium;Experimental Medicine Unit, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; #Immunobiology, Rega Institute for Medical Research, K.U. Leuven, Leuven, Belgium

关键词: vaccine;    interleukin;    chemokine;    cross-linking;    antigen;   

DOI  :  10.1189/jlb.1210699

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Anticytokine auto-vaccination is a powerful tool for the study of cytokine functions in vivo but has remained rather esoteric as a result of numerous technical difficulties. We here describe a two-step procedure based on the use of OVA multimers purified by size exclusion chromatography after incubation with glutaraldehyde at pH 6. When such polymers are incubated with a target protein at pH 8.5 to deprotonate reactive amines, complexes are formed that confer immunogenicity to self-antigens. The chemokine GCP-2/CXCL6, the cytokines GM-CSF, IL-17F, IL-17E/IL-25, IL-27, and TGF-β1, and the MMP-9/gelatinase B are discussed as examples. mAb, derived from such immunized mice, have obvious advantages for in vivo studies of the target proteins. Using a mAb against GCP-2, obtained by the method described here, we provide the first demonstration of the major role played by this chemokine in rapid neutrophil mobilization after Leishmania major infection. Pre-activated OVA multimers reactive with amine residues thus provide an efficient carrier for auto-vaccination against 9–90 kDa autologous proteins.

【 授权许可】

Unknown