Enhancement of Sindbis virus self-replicating RNA vaccine potency by linkage of herpes simplex virus type 1 VP22 protein to antigen

Recently, self-replicating and self-limiting RNA vaccines (RNA replicons) h ave emerged as an important form of nucleic acid vaccines. Self-replicating RNA eventually causes lysis of transfected cells and does not raise the co ncern associated with naked DNA vaccines of integration into the host genom e. This is particularly important for development of vaccines targeting pro teins that are potentially oncogenic. However, the potency of RNA replicons is significantly limited by their lack of intrinsic ability to spread in v ivo. The herpes simplex virus type 1 protein VP22 has demonstrated the rema rkable property of intercellular transport and provides the opportunity to enhance RNA replicon vaccine potency. We therefore created a novel fusion o f VP22 with a model tumor antigen, human papillomavirus type 16 E7, in a Si ndbis virus RNA replicon vector, The linkage of VP22 with E7 resulted in a significant enhancement of E7-specific CD8(+) T-cell activities in vaccinat ed mice and converted a less effective RNA replicon vaccine into one with s ignificant potency against E7-expressing tumors. These results indicate tha t fusion of VP22 to an antigen gene may greatly enhance the potency of RNA replicon vaccines.