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

Chien Hung Chen, Tian Li Wang, Chien Fu Hung, Yanqin Yang, Richard A. Young, Drew M. Pardoll, T. C. Wu

Research output: Contribution to journalArticle

Abstract

Nucleic acid vaccines represent an attractive approach to generating antigen-specific immunity because of their stability and simplicity of delivery. However, there is still a need to increase the potency of DNA vaccines. Using human papillomavirus type 16 E7 as a model antigen, we evaluated the effect 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 frequency of E7-specific CD8+ T cells by at least 30-fold relative to vaccines containing the wild-type E7 gene. More importantly, this fusion converted a less effective vaccine into one with significant potency against established E7-expressing tumors. Surprisingly, E7-HSP70 fusion vaccines exclusively targeted CD8+ T cells; immunological and antitumor effects were completely CD4-independent. These results indicate that fusion of HSP70 to an antigen gene may greatly enhance the potency of DNA vaccines via CD8-dependent pathways.

Original languageEnglish (US)
Pages (from-to)1035-1042
Number of pages8
JournalCancer Research
Volume60
Issue number4
StatePublished - Feb 15 2000

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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