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[Enhancing immunogenicity of pres antigen of hepatitis B virus by fusing genetically it with interleukin-2]
Objective:
To combine the bioactivities of human interleukin-2 (IL-2) with entire preS antigen of hepatitis B virus (HBV), and search for specific immunotherapeutic agent against chronic hepatitis B.
Methods:
A chimeric gene composed of preS gene from HBV DNA and human IL-2 cDNA was constructed by using polymerase chain reaction and genetic engineering methods, and a novel type of chimeric protein (IL-2-preS) was expressed with high efficiency in E. coli transformed by the chimeric gene clone.
Results:
It was confirmed that the chimeric protein retained the full bioactivities of natural IL-2 and preS molecules, such as maintaining CTLL cells to proliferate, with the specific activity being about 10(7)u/mg protein, and binding with monoclonal antibodies against preS1 and preS2 and polymerized human serum albumin (PHSA), etc. It was shown that the titer of antibody against preS antigen in mice induced by IL-2-preS was 9, 11 and 13 times more than those induced by a mixture of IL-2 with preS antigen, MS-2-preS chimeric protein and preS antigen alone, respectively.
Conclusion:
IL-2-preS potentiates immunogenecity of preS antigen and enhances immune responses of human bodies against preS antigen. In addition, IL-2-preS is of double targetting effect in human bodies, and may be used as a new generation of immunotherapeutic agent for chronic hepatitis B and hepatocellular carcinoma.