title: Use of a Clostridium perfringens vector to express high levels of SIV p27 protein for the development of an oral SIV vaccine.
abstract: Clostridium perfringens is a normal bacterial flora of the small and large intestines of humans and other animals. The current study investigates the potential use of a noncytotoxic C. perfringens as an oral vaccine vehicle for expression and intestinal delivery of a large amount of SIV antigens. Here we report the construction of a recombinant C. perfringens vaccine vector expressing high levels of SIV p27 during sporulation. Following oral administration of this recombinant C. perfringens vaccine vector to mice, large amounts of intact p27 protein were detected in the terminal ileum where the majority of Peyer's Patches (PPs) are located. Furthermore, dendritic cells (DCs) beneath the mucosal surface in the PPs were able to capture SIV p27 antigen, when PPs were exposed to C. perfringens expressing SIV p27 antigen. In addition, uptake of C. perfringens was able to induce maturation of mouse DCs. These results support the potential use of C. perfringens as an oral SIV/HIV vaccine vector.
authors.affiliation: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, School of Medicine, University of Pittsburgh, PA 15261, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Ruth
authors.initials: R
authors.lastname: Helmus
authors.forename: Bruce
authors.initials: B
authors.lastname: McClane
authors.forename: Rosemary
authors.initials: R
authors.lastname: Hoffman
authors.forename: Simon
authors.initials: S
authors.lastname: Watkins
authors.forename: Tom
authors.initials: T
authors.lastname: Wehrli
authors.forename: Phalguni
authors.initials: P
authors.lastname: Gupta
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000956:Antigens, Viral / Q000032:analysis / Q000096:biosynthesis; D002454:Cell Differentiation; D003016:Clostridium perfringens / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D017353:Gene Deletion; D015683:Gene Products, gag / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D005822:Genetic Vectors; D007082:Ileum / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010581:Peyer's Patches / Q000276:immunology / Q000382:microbiology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology; D018449:SAIDS Vaccines / Q000008:administration & dosage* / Q000096:biosynthesis / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology
chemical_list: D000956:Antigens, Viral; C066594:Gag protein p27, Simian immunodeficiency virus; D015683:Gene Products, gag; D011993:Recombinant Fusion Proteins; D018449:SAIDS Vaccines; D014614:Vaccines, Synthetic