Enhancement of suicidal DNA vaccine potency by linking Mycobacterium tuberculosis heat shock protein 70 to an antigen

Naked DNA vaccines represent an attractive approach for generating antigen- specific immunity because of their stability and simplicity of delivery. Th ere are particular concerns with DNA vaccines however, such as potential in tegration into the host genome, cell transformation, and limited potency Th e usage of DNA-based alphaviral RNA replicons (suicidal DNA vectors) may al leviate the concerns of integration or transformation since suicidal DNA ve ctors eventually cause lysis of transfected cells. To improve further the p otency of suicidal DNA vaccines, we evaluated the effect of linking Mycobac terium tuberculosis heat shock protein 70 (Hsp70) to human papillomavirus t ype 16 (HPV-16) E7 as a model antigen on antigen-specific immunity generate d by a DNA-based Semliki Forest virus (SFV) RNA vector, pSCA1. Our results indicated that this suicidal DNA vaccine containing E7/Hsp70 fusion genes g enerated significantly higher E7-specific T cell-mediated immune responses than vaccines containing the wild-type E7 gene in vaccinated mice. More imp ortantly, this fusion converted a less effective vaccine into one with sign ificant potency against established E7-expressing metastatic tumors. The an titumor effect was predominantly CD8-dependent. These results indicate that linkage of Hsp70 to the antigen may greatly enhance the potency of suicida l DNA vaccines.