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, Andrew Mark Pardoll, Tzyy Choou 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

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Vaccine Potency
DNA Vaccines
HSP70 Heat-Shock Proteins
Vaccines
Antigens
Genes
Immunity
T-Lymphocytes
Human papillomavirus 16
Mycobacterium tuberculosis
Gene Frequency
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Enhancement of DNA vaccine potency by linkage of antigen gene to an HSP70 gene. / Chen, Chien Hung; Wang, Tian-Li; Hung, Chien-Fu; Yang, Yanqin; Young, Richard A.; Pardoll, Andrew Mark; Wu, Tzyy Choou.

In: Cancer Research, Vol. 60, No. 4, 15.02.2000, p. 1035-1042.

Research output: Contribution to journalArticle

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