Cancer immunotherapy using Sindbis virus replicon particles encoding a VP22-antigen fusion

Hum Gene Ther. 2002 Mar 1;13(4):553-68. doi: 10.1089/10430340252809847.


Alphavirus vectors have emerged as a strategy for the development of cancer vaccines and gene therapy applications. The availability of a new packaging cell line (PCL), which is capable of generating alphavirus replicon particles without contamination from replication-competent virus, has advanced the field of vaccine development. This replication-defective vaccine vector has potential advantages over naked nucleic acid vaccines, such as increased efficiency of gene delivery and large-scale production. We have developed a new strategy to enhance nucleic acid vaccine potency by linking VP22, a herpes simplex virus type 1 (HSV-1) tegument protein, to a model antigen. This strategy facilitated the spread of linked E7 antigen to neighboring cells. In this study, we created a recombinant Sindbis virus (SIN)-based replicon particle encoding VP22 linked to a model tumor antigen, human papillomavirus type 16 (HPV-16) E7, using a stable SIN PCL. The linkage of VP22 to E7 in these SIN replicon particles resulted in a significant increase in the number of E7-specific CD8(+) T cell precursors and a strong antitumor effect against E7-expressing tumors in vaccinated C57BL/6 mice relative to wild-type E7 SIN replicon particles. Furthermore, a head-to-head comparison of VP22-E7-containing naked DNA, naked RNA replicons, or RNA replicon particle vaccines indicated that SINrep5-VP22/E7 replicon particles generated the most potent therapeutic antitumor effect. Our results indicated that the VP22 strategy used in the context of SIN replicon particles may facilitate the generation of a highly effective vaccine for widespread immunization.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines*
  • Female
  • Gene Transfer Techniques
  • Immunotherapy*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / immunology*
  • Papillomavirus E7 Proteins
  • Replicon / genetics
  • Replicon / immunology*
  • Sindbis Virus / immunology*
  • Sindbis Virus / physiology
  • Vaccines, DNA
  • Viral Proteins / genetics
  • Viral Proteins / immunology*


  • Cancer Vaccines
  • ICP35 protein, Human herpesvirus 1
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Vaccines, DNA
  • Viral Proteins
  • oncogene protein E7, Human papillomavirus type 16