title: A novel mitogen fusion protein against CD40+ cells with potent vaccine adjuvant properties.
abstract: A large number of infectious diseases caused by viral or bacterial infections are treatable and/or preventable by vaccination. In addition, ongoing research is aimed at the development of vaccines against other types of diseases, including almost all forms of cancer. The efficacy of a vaccine relies on the antigen-specific response by the entire repertoire of immune competent cells. Here, we have generated a powerful mitogen fusion protein, CD40L-FasL-IgFc, which stimulates CD40(+) cells robustly. We found that this specific cell activation is accompanied by increased expression of PRDI-BF1 (Blim-1) RNA, an indicator of terminal B-cell differentiation, in cultures stimulated with CD40L-FasL-IgFc. The addition of specific inhibitors of NF-kappaB and MEK1/2 partially suppressed the observed proliferative effects of CD40L-FasL-IgFc. When tested in vivo, the immune response to influenza HA vaccine was significantly increased by co-administration of CD40L-FasL-IgFc. Moreover, the co-administration of the cDNA expression plasmid encoding CD40L-FasL-IgFc significantly boosted the vaccine response. We now have a unique opportunity to evaluate our novel fusion protein adjuvant, and other similarly constructed fusion proteins, in both protein-based and genetic vaccines.
authors.affiliation: First Department of Internal Medicine, School of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yoshida
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yoshida
authors.forename: Bruce Yong
authors.initials: BY
authors.lastname: Ma
authors.forename: Sebastian
authors.initials: S
authors.lastname: Mikolajczak
authors.forename: David J
authors.initials: DJ
authors.lastname: Kelvin
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ochi
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation; D053222:Fas Ligand Protein / Q000276:immunology*; D006801:Humans; D007252:Influenza Vaccines / Q000276:immunology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012097:Repressor Proteins / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D019013:CD40 Antigens; D053222:Fas Ligand Protein; D007252:Influenza Vaccines; D008934:Mitogens; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C087042:PRDM1 protein, human; D023201:CD40 Ligand; D000074462:Positive Regulatory Domain I-Binding Factor 1