title: Enhancement of DNA vaccine potency by linkage of antigen gene to an HSP70 gene.
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.
authors.affiliation: Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
authors.forename: C H
authors.initials: CH
authors.lastname: Chen
authors.forename: T L
authors.initials: TL
authors.lastname: Wang
authors.forename: C F
authors.initials: CF
authors.lastname: Hung
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: R A
authors.initials: RA
authors.lastname: Young
authors.forename: D M
authors.initials: DM
authors.lastname: Pardoll
authors.forename: T C
authors.initials: TC
authors.lastname: Wu
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; D019496:Cancer Vaccines; D018840:HSP70 Heat-Shock Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D019444:Vaccines, DNA; C059731:oncogene protein E7, Human papillomavirus type 16