Enhancement of DNA vaccine potency through linkage of antigen gene to ER chaperone molecules, ER-60, tapasin, and calnexin

Cheng Tao Lin, Ting Chang Chang, Angel Chao, Elizabeth Dzeng, Yung Kuei Soong, Chien Fu Hung, Chyong Huey Lai

Research output: Contribution to journalArticlepeer-review

Abstract

DNA vaccines have emerged as an attractive approach for generating antigen-specific immunotherapy. Strategies that enhance antigen presentation may potentially be used to enhance DNA vaccine potency. Previous experiments showed that chimeric DNA vaccines utilizing endoplasmic reticulum (ER) chaperone molecules, such as Calreticulin (CRT), linked to an antigen were capable of generating antigen-specific CD8+ T cell immune responses in vaccinated mice. In this study, we tested DNA vaccines encoding the ER chaperone molecules ER-60, tapasin (Tap), or calnexin (Cal), linked to human papillomavirus type 16 (HPV-16) E7 for their abilities to generate E7-specific T cell-mediated immune responses and antitumor effects in vaccinated mice. Our results demonstrated that vaccination with DNA encoding any of these chaperone molecules linked to E7 led to a significant increase in the frequency of E7-specific CD8+ T cell precursors and generated stronger antitumor effects against an E7-expressing tumor in vaccinated mice compared to vaccination with wild-type E7 DNA. Our data suggest that DNA vaccines employing these ER chaperone molecules linked to antigen may enhance antigen-specific CD8+ T cell immune responses, resulting in a significantly more potent DNA vaccine.

Original languageEnglish (US)
Pages (from-to)279-287
Number of pages9
JournalJournal of biomedical science
Volume12
Issue number2
DOIs
StatePublished - Mar 2005

Keywords

  • Calnexin
  • DNA vaccines
  • E7
  • ER-60
  • Human papillomavirus (HPV)
  • Immunotherapy
  • Tapasin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Pharmacology (medical)

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