Enhancement of Sindbis Virus Self-Replicating RNA Vaccine Potency by Linkage of Mycobacterium Tuberculosis Heat Shock Protein 70 Gene to an Antigen Gene

Self-replicating RNA vaccines (RNA replicons) have emerged as an effective strategy for nucleic acid vaccine development. Unlike naked DNA vaccines, RNA replicons eventually cause lysis of transfected cells and therefore do not raise the concern of integration into the host genome. We evaluated the effect of linking human papillomavirus type 16 (HPV-16) E7 as a model antigen to Mycobacterium tuberculosis heat shock protein 70 (HSP70) on the potency of antigen-specific immunity generated by a Sindbis virus self-replicating RNA vector, SINrep5. Our results indicated that this RNA replicon vaccine containing an E7/HSP70 fusion gene generated significantly higher E7-specific T cell-mediated immune responses in vaccinated mice than did vaccines containing the wild type E7 gene. Furthermore, our in vitro studies demonstrated that E7 antigen from E7/HSP70 RNA replicon-transfected cells can be processed by bone marrow-derived dendritic cells (DCs) and presented more efficiently through the MHC class I pathway than can wild-type E7 RNA replicon-transfected cells. More importantly, the fusion of HSP70 to E7 converted a less effective vaccine into one with significant potency against E7-expressing tumors. This anti-tumor effect was dependent on NK cells and CD8+ T cells. These results indicated that fusion of HSP70 to an antigen gene may greatly enhance the potency of self-replicating RNA vaccines. Description (Set) Proposed Use (Set) The technology may be used for the development of preventive and therapeutic vaccines for infectious diseases and cancers in human and animals.

Inventor(s): Wu, T.C.

Type of Offer: Licensing



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