Clostridial dermatitis (cellulitis) in turkeys is associated with significant economic loss to turkey producers in USA and elsewhere in Europe. Clostridium septicum has been consistently isolated from Clostridial dermatitis lesions in turkeys and there is ample evidence to indicate that Clostridium septicum plays a primary role in causing Clostridial dermatitis in turkeys. We reproduced Clostridial dermatitis in turkeys post administration of C septicum isolates from field cases. At present there are no commercially available vaccines against C. septicum infection in poultry and current biosecurity measures are not effective in controlling Clostridial dermatitis. It has been shown that toxoids made from clostridial exotoxins are effective vaccine candidates. Unfortunately, toxoids must be administered parenterally and provide only short term immunity which, makes them unfeasible to use in the commercial turkey industry. Therefore, a robust vaccine delivery system to control clostridial dermatitis is urgently needed. Ideally, the vaccine should be inexpensive to produce, stable, safe, easy to use and efficacious. Our hypothesis is that the oral administration of outer membrane vesicles (OMV) containing an adequate amount of immunogenic toxoids can elicit protective immunity thereby reducing the incidence of cellulitis in commercial turkeys. Outer membrane vesicles are attractive candidates for vaccine delivery platforms because of their immunogenic properties, self-adjuvanticity ability to be taken up by mammalian cells, and capacity for enhancement by recombinant engineering. Outer membrane vesicles as vaccine carriers is an emerging technology as research exposes more of the molecular intricacies of vesiculation and how the vesicles can be co-opted to fight infectious bacterial agents. In this study, we propose to develop a hypervesiculated strain of an E. coli mutant with modification of Lipid A (1-dephosphorylated). This mutant will be used to produce OMV nanoparticles containing C. septicum antigen (α) that can be used as a vaccine in turkeys against C. septicum infection. This project is designed with a goal of developing an effective vaccine for prevention of Clostridial dermatitis in turkeys.