Enhancement of DNA vaccine potency by linkage of antigen gene to an HSP70 gene.
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.
Chen
C H
CH
Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
Wang
T L
TL
Hung
C F
CF
Yang
Y
Y
Young
R A
RA
Pardoll
D M
DM
Wu
T C
TC
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*
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