title: Encoded novel forms of HSP70 or a cytolytic protein increase DNA vaccine potency.
abstract: In humans, DNA vaccines have failed to demonstrate the equivalent levels of immunogenicity that were shown in smaller animals. Previous studies have encoded adjuvants, predominantly cytokines, within these vaccines in an attempt to increase antigen-specific immune responses. However, these strategies have lacked breadth of innate immune activation and have led to disappointing results in clinical trials. Damage associated molecular patterns (DAMPs) have been identified as pattern recognition receptor (PRR) agonists. DAMPs can bind to a wide range of PRRs on dendritic cells (DCs) and thus our studies have aimed to utilize this characteristic to act as an adjuvant in a DNA vaccine approach. Specifically, HSP70 has been identified as a DAMP, but has been limited by its lack of accessibility to PRRs in and on DCs. Here, we discuss the promising results achieved with the inclusion of membrane-bound or secreted HSP70 into a DNA vaccine encoding HIV gag as the model immunogen.
authors.affiliation: a Discipline of Surgery ; the University of Adelaide; Basil Hetzel Institute ; Adelaide , SA Australia.
authors.forename: Tamsin
authors.initials: T
authors.lastname: Garrod
authors.forename: Branka
authors.initials: B
authors.lastname: Grubor-Bauk
authors.forename: Stanley
authors.initials: S
authors.lastname: Yu
authors.forename: Tessa
authors.initials: T
authors.lastname: Gargett
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Gowans
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D054353:Perforin / Q000235:genetics / Q000378:metabolism*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D018840:HSP70 Heat-Shock Proteins; D019444:Vaccines, DNA; D054353:Perforin
keywords: DNA vaccine; adjuvant; cytolytic; heat shock protein; protective immunity