lmmunogenicity of HER2 vaccine containing p-nitrophenylalanine / 中国药科大学学报

In order to delete the immune tolerance of self-protein HER2 and produce an efficient immune response,the genetic code expansion technique was employed to introduce the immunogenic amino acid p-nitro-phenylalanine into the position 5 ,26 and 79 of the HER2 fragment and HER2 mutants containing p-nitropheny-lalanine were obtained.Prototype and mutant HER2 molecules with a purity of more than 95% were obtained through a nickel affinity column.Immunogenicity analysis of the HER2 vaccine showed that pNO2Phe79HER2 was able to produce high titer cross-reactive antibodies in C57BL/6 mice and that the mouse antisera could recognize SKBR-3 cells with intact HER2 receptor extracellular domain and cleave HER2 highly expressed HER2 +B16F10 cells through ADCC effect.These findings suggested that pNO2Phe79HER2 which incorporates p-nitro-phenylalanine could be used as a tumor vaccine candidate targeting HER2.

Protective effects of p-nitrophenylalanine-containing BAFF vaccine on lupus nephritis model mice / 中国药科大学学报

In order to verify whether p-nitrophenylalanine-containing BAFF vaccine can be used as a candidate molecule for the treatment of autoimmune diseases with BAFF over-expression,a soluble mutant of B cell activating factor belonging to the TNF Family (smBAFF) and its pNO2Phe mutant(pNO2Phe65smBAFF),which site specific incorporated pNO2Phe at position 65 of smBAFF,were expressed and purified.In order to evaluate the feasibility of using pNO2Phe65 smBAFF to treat BAFF-over-expressed autoimmune diseases,we investigate its Lymphocyte-stimulating capacity,immunogenicity and inhibitory effect of serum on biological activity of natural BAFF.The pharmacological activity of pNO2Phe65 smBAFF was evaluated using a cGVHD(graft-versus-host disease) induced SLE mouse model.Results indicated that pNO2Phe65 smBAFF,could bind to mouse lymphocytes but could not promote the proliferation of mouse lymphocytes.Moreover,the incorporation of pNO2Phe significantly increased the immunogenicity and induced cross-antibody,which can inhibit the biological activity of natural BAFF.In cGVHD induced SLE mouse model,pNO2Phe65 smBAFF can significantly reduce the symptoms of the disease and play a therapeutic role.Therefore,pNO2Phe65 smBAFF can be used as a candidate molecule for the treatment of autoimmune diseases with BAFF over-expression.