title: Enhancement of DNA vaccine potency through linkage of antigen gene to ER chaperone molecules, ER-60, tapasin, and calnexin.
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.
authors.affiliation: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
authors.forename: Cheng-Tao
authors.initials: CT
authors.lastname: Lin
authors.forename: Ting-Chang
authors.initials: TC
authors.lastname: Chang
authors.forename: Angel
authors.initials: A
authors.lastname: Chao
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Dzeng
authors.forename: Yung-Kuei
authors.initials: YK
authors.lastname: Soong
authors.forename: Chien-Fu
authors.initials: CF
authors.lastname: Hung
authors.forename: Chyong-Huey
authors.initials: CH
authors.lastname: Lai
mesh_terms: D000818:Animals; D017920:Antiporters / Q000737:chemistry*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D037281:Calnexin / Q000737:chemistry*; D019496:Cancer Vaccines / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000737:chemistry*; D016207:Cytokines / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry*; D007167:Immunotherapy / Q000379:methods*; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018832:Molecular Chaperones / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000737:chemistry; D050725:Papillomavirus E7 Proteins; D010957:Plasmids / Q000378:metabolism; D013997:Time Factors; D019444:Vaccines, DNA
chemical_list: D017920:Antiporters; D019496:Cancer Vaccines; D016207:Cytokines; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D019444:Vaccines, DNA; C059731:oncogene protein E7, Human papillomavirus type 16; C107762:tapasin; D037281:Calnexin; D004247:DNA; D003546:Cysteine Endopeptidases; C077733:ER-60 protease