Enhancement of DNA vaccine potency by linkage of antigen gene to an HSP70 gene

Nucleic acid vaccines represent an attractive approach to generating antige n-specific immunity because of their stability and simplicity of delivery. However, there is still a need to increase the potency of DNA vaccines, Usi ng human papillomavirus type 16 E7 as a model antigen, we evaluated the eff ect of linkage to Mycobacterium tuberculosis heat shock protein 70 (HSP70) on the potency of antigen-specific immunity generated by naked DNA vaccines . We found that vaccines containing E7-HSP70 fusion genes increased the fre quency of E7-specific CD8+ T cells by act Least 30-fold relative to vaccine s containing the wild-type E7 gene. More importantly, this fusion converted a less effective vaccine into one with significant potency against establi shed E7-expressing tumors. Surprisingly, E7-HSP70 fusion vaccines exclusive ly targeted CD8+ T cells; immunological and antitumor effects were complete ly CD4-independent. These results indicate that fusion of HSP70 to an antig en gene may greatly enhance the potency of DNA vaccines via CD8-dependent p athways.