Use of a Clostridium perfringens vector to express high levels of SIV p27 protein for the development of an oral SIV vaccine.
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.
Chen
Yue
Y
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, School of Medicine, University of Pittsburgh, PA 15261, USA.
Helmus
Ruth
R
McClane
Bruce
B
Hoffman
Rosemary
R
Watkins
Simon
S
Wehrli
Tom
T
Gupta
Phalguni
P
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
D000956:Antigens, Viral; C066594:Gag protein p27, Simian immunodeficiency virus; D015683:Gene Products, gag; D011993:Recombinant Fusion Proteins; D018449:SAIDS Vaccines; D014614:Vaccines, Synthetic