Objective: Poultry Colibacillosis caused by different Avian Pathogenic E.coli (APEC) serotypes that accompanied by different symptoms and commercial loses in poultry industry. Different studies were done to prevent disease such as vaccination with killed, live attenuated, recombinant and DNA vaccine. In this study a homologous vaccine component of E. coli O2:K1 was produced by use of bacterial ghost technique. Controlled expression of bacteriophage PhiX 174 lysis gene E was done with transformation of bacteria by pmET32b plasmids. Temperature controlled expression of this gene caused tunnels and holes in the E. coli O2:K1 cell wall, leading to loss of cytoplasmic contents. Confirmation of E. coli O2:K1 ghost production was done by scanning electron microscopy and determination of 48 hours culture and colony forming units. Materials & Methods: To evaluate the efficiency of this produced ghosts as vaccine and elicit cellular and humoral immune responses, 85 one day old chickens from Ross 308 breed were divided into the following 5 groups; group 1 (non-immunized control), group 2 (vaccine administered by injection of E. coli O2:K1 killed vaccine), group 3 (vaccine administered by injection of E. coli O2:K1 ghost), group 4 (vaccine administered by inhalation of E. coli O2:K1 ghost), and group 5 (neither immunized, nor challenged as negative control). The three groups of 2, 3, and 4 were received vaccines at days 7, 14, and 22. Groups 1 to 4 were challenged with the wild serotype at day 33. Sampling were done at days 14, 25 and 38. Evaluation of post-mortem lesions by scoring of carcasses a humoral immune responses by measuring of IgG (IgY) and IgA were done in all groups. Results & Conclusions: Results showed that chickens injected with the bacterial ghost and the killed vaccine had the best immune response and protection compare to control groups. (P<0/05).

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