title: Co-immunization with an HIV-1 Tat transduction peptide-rotavirus enterotoxin fusion protein stimulates a Th1 mucosal immune response in mice.
abstract: The cholera toxin B subunit (CTB) and a 12 aa HIV-1 Tat transduction peptide were genetically linked to a 90 aa peptide from the murine rotavirus non-structural enterotoxin protein (NSP4) for comparison of receptor directed and transduction peptide mediated antigen targeting to the gut associated lymphoid tissues for enhanced protection against rotavirus infection. Oral immunization with Tat-NSP4(90) fusion protein isolated from Escherichia coli generated detectable anti-NSP4(90) IgG titers in mice. CTB-NSP4(90) fusion protein stimulated higher serum IgG titers than CTB fused to a 22 aa immunodominant epitope NSP4(22) indicating the presence of additional immunogenic epitopes in the NSP4(90) peptide. Mice immunized with CTB-NSP4(22) stimulated high IgG2a antibody levels suggesting a dominant Th1 lymphocyte response. However, mice immunized with CTB-NSP4(90) generated similar levels of IgG1 and IgG2a suggesting equal stimulation of Th1 and Th2 responses. Mice co-immunized with CTB-NSP4(90) and Tat-NSP4(90) fusion proteins generated dominant IgG2a levels indicating that the two ligands co-operate to generate an increased Th1 response.
authors.affiliation: Department of Biochemistry and Microbiology and Center for Molecular Biology and Gene Therapy, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA.
authors.forename: Tae-Geum
authors.initials: TG
authors.lastname: Kim
authors.forename: Natasha
authors.initials: N
authors.lastname: Befus
authors.forename: William H R
authors.initials: WH
authors.lastname: Langridge
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000956:Antigens, Viral / Q000096:biosynthesis; D020895:Enterocytes / Q000378:metabolism; D004768:Enterotoxins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000235:genetics; D005455:Fluorescent Antibody Technique; D015696:Gene Products, tat / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D008024:Ligands; D008163:Luminescent Measurements; D051379:Mice; D012401:Rotavirus / Q000737:chemistry*; D018417:Th1 Cells / Q000276:immunology*; D014611:Vaccination; D014760:Viral Fusion Proteins / Q000378:metabolism / Q000494:pharmacology*; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000956:Antigens, Viral; D004768:Enterotoxins; D000939:Epitopes; D015696:Gene Products, tat; D007074:Immunoglobulin G; D008024:Ligands; D014760:Viral Fusion Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus