In this study, a set of molecular biotechnologies were used to efficiently express and obtain soluble fusion protein of alphaepsilon-toxin (alpha-epsilon-toxin) derived from Clostridium perfringens in Escherichia coli. We have successfully obtained a soluble fusion protein of alpha-epsilon-toxin for the first time with efficient expression in E. coli system by conducting codon optimization, removing the signal peptide, selecting sequences of higher hydrophilicity and antigenicity, removing the lethal gene and optimizing the expression conditions. Noticeable rise of antibody level was detected in the serum of mice after immunization with the expressed protein. The immunized mice got protected against C. perfringens type A, B, C and D with the survival rate of 100,90,85 and 100%, respectively. (C) 2019 Friends Science Publishers