title: Intradermal administration of DNA vaccines combining a strategy to bypass antigen processing with a strategy to prolong dendritic cell survival enhances DNA vaccine potency.
abstract: Intradermal vaccination via gene gun efficiently delivers DNA vaccines into dendritic cells (DCs) of the skin, resulting in the activation and priming of antigen-specific T cells in vivo. We have previously demonstrated that intradermal delivery of DNA vaccines encoding single-chain trimer (SCT) composed of the most immunogenic epitope of human papillomavirus type 16 (HPV-16) E6 protein (aa49-57), beta2-microglobulin, and MHC class I heavy chain (SCT-E6) can bypass antigen processing and lead to stable cell-surface presentation of E6 peptides. We also showed that co-administration of DNA vaccines with DNA encoding anti-apoptotic proteins can prolong the survival of DNA-transduced DCs, resulting in significant enhancement of antigen-specific CD8(+) T cell immune responses. In the current study, we hypothesized that combining the SCT strategy and antiapoptotic strategy may further enhance DNA vaccine potency by augmenting antigen-specific CD8(+) T cell immune responses and antitumor effects in vaccinated mice. Here, we show that C57BL/6 mice vaccinated with SCT-E6 DNA combined with antiapoptotic protein Bcl-xL DNA generated enhanced E6-specific CD8(+) T cell immune responses compared to mice vaccinated with SCT-E6 DNA and a non-functional mutant Bcl-xL (mtBcl-xL) DNA. Furthermore, we show that mice treated with SCT-E6 and Bcl-xL DNA generated enhanced anti-tumor effects against E6-expressing tumor cells (TC-1/Luciferase) compared to mice treated with SCT-E6 and mtBcl-xL DNA.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Huang
authors.forename: Chih-Ping
authors.initials: CP
authors.lastname: Mao
authors.forename: Shiwen
authors.initials: S
authors.lastname: Peng
authors.forename: Liangmei
authors.initials: L
authors.lastname: He
authors.forename: Chien-Fu
authors.initials: CF
authors.lastname: Hung
authors.forename: T-C
authors.initials: TC
authors.lastname: Wu
mesh_terms: D000818:Animals; D002470:Cell Survival; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D004333:Drug Administration Routes; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D007271:Injections, Intradermal; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000276:immunology; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D000939:Epitopes; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D012097:Repressor Proteins; D019444:Vaccines, DNA