title: A novel, helminth-derived immunostimulant enhances human recall responses to hepatitis C virus and tetanus toxoid and is dependent on CD56+ cells for its action.
abstract: We have described previously an immunostimulant derived from Onchocerca volvulus, the helminth parasite that causes onchocerciasis. Recombinant O. volvulus activation-associated secreted protein-1 (rOv-ASP-1) was a potent adjuvant for antibody and cellular responses to protein, polypeptide and small peptide antigens. Our aims were to determine whether rOv-ASP-1 is immunostimulatory for human peripheral blood mononuclear cells (PBMC) and, if so, whether it could augment cellular responses against human pathogen antigens in vitro. Cytokines from rOv-ASP-1-stimulated human PBMC were measured by a fluorescence activated cell sorter-based multiplex assay. Recall responses of normal healthy donor (NHD) and chronic hepatitis C virus (c-HCV)-infected patient PBMC to tetanus toxoid (TT) or HCV core (HCVco) antigen, respectively, were measured by interferon-gamma enzyme-linked immunospot assays. Interferon-gamma was the predominant cytokine induced by rOv-ASP-1. 77.3% of NHD anti-TT and 88.9% of c-HCV anti-HCVco responses were enhanced by rOv-ASP-1. The immunostimulant effect was dependent upon contact between CD56+ and CD56- fractions of PBMC. We have described a helminth-derived protein that can act as an immunostimulant for human recall responses in vitro to TT and, perhaps more importantly, HCV antigens in patients with chronic HCV infection. Our longer-term goal would be to boost anti-viral responses in chronic infections such as HCV.
authors.affiliation: iQur Ltd, Mailpoint 811, Southampton General Hospital, Southampton, UK. angus336@btinternet.com
authors.forename: A J
authors.initials: AJ
authors.lastname: MacDonald
authors.forename: N A
authors.initials: NA
authors.lastname: Libri
authors.forename: S
authors.initials: S
authors.lastname: Lustigman
authors.forename: S J
authors.initials: SJ
authors.lastname: Barker
authors.forename: M A
authors.initials: MA
authors.lastname: Whelan
authors.forename: A E
authors.initials: AE
authors.lastname: Semper
authors.forename: W M
authors.initials: WM
authors.lastname: Rosenberg
mesh_terms: D000276:Adjuvants, Immunologic; D000328:Adult; D000368:Aged; D000947:Antigens, Helminth / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D019002:CD56 Antigen / Q000032:analysis; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015801:Helminth Proteins / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D016131:Lymphocyte Subsets / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000947:Antigens, Helminth; D000956:Antigens, Viral; D019002:CD56 Antigen; D016207:Cytokines; D015801:Helminth Proteins; D018836:Inflammation Mediators; C414408:Ov-ASP-1 protein, Onchocerca volvulus; D011994:Recombinant Proteins; D013745:Tetanus Toxoid; D007371:Interferon-gamma