Enhancement of suicidal DNA vaccine potency by linking Mycobacterium tuberculosis heat shock protein 70 to an antigen.
Naked DNA vaccines represent an attractive approach for generating antigen-specific immunity because of their stability and simplicity of delivery. There are particular concerns with DNA vaccines however, such as potential integration into the host genome, cell transformation, and limited potency. The usage of DNA-based alphaviral RNA replicons (suicidal DNA vectors) may alleviate the concerns of integration or transformation since suicidal DNA vectors eventually cause lysis of transfected cells. To improve further the potency of suicidal DNA vaccines, we evaluated the effect of linking Mycobacterium tuberculosis heat shock protein 70 (Hsp70) to human papillomavirus type 16 (HPV-16) E7 as a model antigen on antigen-specific immunity generated by a DNA-based Semliki Forest virus (SFV) RNA vector, pSCA1. Our results indicated that this suicidal DNA vaccine containing E7/Hsp70 fusion genes generated significantly higher E7-specific T cell-mediated immune responses than vaccines containing the wild-type E7 gene in vaccinated mice. More importantly, this fusion converted a less effective vaccine into one with significant potency against established E7-expressing metastatic tumors. The antitumor effect was predominantly CD8-dependent. These results indicate that linkage of Hsp70 to the antigen may greatly enhance the potency of suicidal DNA vaccines.
Hsu
K F
KF
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Hung
C F
CF
Cheng
W F
WF
He
L
L
Slater
L A
LA
Ling
M
M
Wu
T C
TC
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009856:Oncogene Proteins, Viral / Q000276:immunology; D027383:Papillomaviridae / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D012672:Semliki forest virus / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
D000914:Antibodies, Viral; D000956:Antigens, Viral; D018840:HSP70 Heat-Shock Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D019444:Vaccines, DNA; C059731:oncogene protein E7, Human papillomavirus type 16