title: Synergistic antibody induction by antigen-CD40 ligand fusion protein as improved immunogen.
abstract: Full scale B-cell activation requires not only B-cell receptor (BCR) engagement with antigen, but also costimulatory signals provided by T helper cells through the CD40-CD40 ligand (CD40L) interaction. It is hypothesized that a fusion protein of an antigen and soluble CD40L (CD40LT) would selectively target the costimulation to antigen-specific B cells, leading to synergy in the antibody response. This hypothesis was investigated by fusing green fluorescence protein (GFP), a generic antigen, with mouse CD40LT. Studies revealed that immunization in mice with the plasmid encoding GFP-CD40LT fusion protein led to synergistic induction of GFP-specific antibodies, while control plasmid(s) for GFP, CD40LT, or GFP plus CD40LT did not. Immunization with a single dose of the fusion protein also provoked a vigorous GFP-specific immunoglobulin G1 antibody response, but not other antibody isotypes. These results suggest that GFP-CD40LT fusion protein induces a GFP-specific B-cell activation and antibody response in an antigen-guided fashion. The potential application of this novel strategy in vaccine development is discussed.
authors.affiliation: Bascom Palmer Eye Institute, Department of Ophthalmology and Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL 33136, USA. wli@med.miami.edu
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology*; D049452:Green Fluorescent Proteins / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D008211:Lymphocyte Cooperation / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010957:Plasmids / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D019013:CD40 Antigens; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D023201:CD40 Ligand; D049452:Green Fluorescent Proteins